Document 3QxwQJKYQNbJ2YvY4qGRjgvMn

I Town Hail, Ssnsae I*kt, M. Y. \ Feb. ?, % amd , 1955 WV-03388 Acknowledgments t Crarefu? acknowledgment is made to all the participants who contributed papers this Conference. Appreciation is expressed ato to: American Medical Association for cooperation in printing the Conference transactions ' fVofessor Philip Drinker (or editorial advice Thomas M. Durkan for preparing index Edward L. Gockeler for photography Secretarial Staff of the Saranac Laboratory for preparing manuscripts Staff of the Saranac Laboratory for preparing Conference hatts add exhibits . G. W. B. $chews, M.D>, DSc., Editor FOREWORD -----V -- V/ For many years the Saranac laboratory, ol Saranac Lake, N. Y., and the McIntyre Research Foundation, of Toronto, Canaria, have been conducting research alfrPg somewhat parallel lines. For the past five years the McIntyre Research Foundation has held its Annual Meeting on Silicosis and Alaminum Therapy in various dries in the United Sates and Canada, while The Saranac Laboratory, since 1934, has*sponsored a series of Symposia on Industrial Pulmonary Diseases Saranac Lake. These two organizations pooled their knowledge and resources for this conference, and the proceedings au documented in this volume, Saranac Lake, for many years a center for the study and treatment of pulmonary tuberculosis and other chronic chest diseases and, moreover, a world-renowned recreational resort, provided a unique and attractive setting for the conference. The sessions, which were very well attended, attracted more than 250 persons, including visitors from the United States, Canada, South America, France, Eng land, Scotland, Wales, India, and the Union of South Africa. The pronouncements in reaped of occupational chest diseases, which have been emanating from The Saranac Laboratory and more recently from the McIntyre Research Foundation, have in the past influenced medical, engineering, and legal thinking in terms of these diseases. The views expressed at the preceding con ferences have guided management, labor, compensation courts, physicians, engi neers, lawyers, and educators not only in the United States and Canada but in many other countries. It is hoped that the record of this most recent conference will in equal measure also prove of benefit to those who seek firsthand information and guidance concerning the problem of occupational chest diseases. The prediction that this will be so is strong, because practically every paper presented at the con ference was based on original research. '1 1 Amthojj* J. Lanza, MX*., 4 Csnferexe* CJudrmaa Emeritus Professor f Industrial Medicine New York University-Bellevue Medical Center I j MdNTYRE-SARANAC CONFERENCE PROGRAM COMMITTEE 19S5 S A. J. Lanza, M.D. C P. McCori>, M-D. D. A. I*ww, M.D.......... Chairman Acting Chairman J, W. G. Hannon, M-D T. L. Shipkan, M.D. G. W. fi. Scbexeks, UD., D.Sc. L R. Bunn --Organizer Secretary Conference Program Stuient J. Gcftenl CHdCarey P, McCord, MU., Cooaatent Industrial Medicine, Injfrtate of Industrial Health, University of Michigan, Artf Ajhor, Mich. t Afumintan kt Control d Silfcosii Moderator: William A. Sawyer, MU., KeikaJ Cbosttltsot, taengttonal Association of Machinist*. Rochester, K. V. Daewssae*: Pmd G. Br&art, MJ3, CdawRa&g Reertgewdogs*. Tareowm, Pa. 1 EpWenaology of Silkosi* and Occupational Ow Disease t Moderator: Tfiomos L, SMf-mon, M.D., Health Division Leader, Los Alanx* Scientific Laboratory, Los Abac*, New Mexico Discussant: Philip printer, 5LD,, Professor of Xachostriaf Kygk&e, Ham*4 UnivetuQ' School of Public Health. Boston, Uui. A TV* E'eahatic* of Experimental Research oo Dint Diseases Moderator^ UadUy A. Ind*., MUU Kwfieai Director, Alsaniataa Camp*oy of America, Pittsburgh, Pa, Piwssaot: Norton Nelson, PkU^ Chairman, lastituw of Industrial Medicine, New York Uctvcrsity-Beikvne Medic** Cesser, New York, H. Y. L Ue&eo-Legai and CUttkal Aspects of Pulmonary Daabi&cy Moderator: /tea Seboufi*, Q., Coutaei W> $a4c Xsnestc* Producer* Assooatke, Montreal, Quebec Discussant: Warren A. Coot, iLd,, Astoeaie Professor, Industrial Health and Hygiene, University of Michigan School of Pub&e Heaith, Aa Arirp Mich 6 Experiaestai w*d Engineering Aspects of Ocsrpatiou! Chest Diseases \ f Moderator; Ang*s U Cooatkdl, Manager, McIntyre.Research PoomUtioo, Schumacher, Ontario 4 Epilogue: Corey P. McCord, MU. | 7 Conferencetfiartfuet MasterW Ceremonies: Manfred BotodUcK Director of Health and Safety, Lead Industries , Association New Yock, N Y. j| Leroy If. Gardner Memorial Address; Pod S. Rickards, MU-, Sentos CorudtasA, ^ Memorial Medical Center, Salt Lake City, Utah | Personal Impressions C Edwasd LWingM^i Tfudeaa and Edward R. Baldwin; Hugh M. ' Af^)v S*j*nat 5-ake, N. Y. 4 1 \ Contents rt* Foreword.......................................... Program Cogaelttec............................................................ ............. .*.................................. *(* Coafereoee Prognaa Lev..................... .................................................................................. .. v v.. Prologue Carey F. McCord, MX/,, Ann Arbor, Mick........................... ................... . ... I The Objectives tod Achievements of (be Uelnlyr* Research Foundation Fronds B. Tntdeeu, MX* Saranac lake, N. Y.......................................................... .. 2 The Contribution of fee Saranac Laboratory to Research on Cheat Diseases f, . D. Few, M' * Toronto, Canada....... -........................ ......................... .............. . .. 4 ^ Comparative Vascular Pathology of OtoapationaJ Chest Dishes l/ G. W. H. Schemers, MX* DSc* Saranac Uke, N. Y................................................ .. 7 Ttx Value of Loos Biopsy so fee Dugsaow of Occupational Pulmonary Diseases H. S. Van Ordftrond. MX.; Donald S. Bffler, MX.; Lawrence 7. McCormack, MX.,>r-s, and John B. Hoard, MX* Cleveland.... ............................................................... (76 ' Ocatpatiooal Oaeat Diseases is Gold Misers G. W. H. Sehefere, MX* DSe,, Saranac lake, N. Y.....................................................$$ Ac&omp&tsBcats t& fee Rpidenuotogie Stud; of Silicosis in the United States H. N. Doyle, BS.; Victoria M. Trtuko, AX.; IP. M. Gajaier, DSc., and S. E. Miller, MX* Washington, D. C...---................................. . 4$ SHkmfe jb Caaada H. F. Parkinson, M., Toronto, Canada. 56 Gxamcotary oq Refefe&ees by W. F. Parkinsoa Cotcarting fee Siltaatis Problen Andrew R. RiddcU, M3* DFJl* Toronto, Canada.........................................................6J Tale Fodsaocceiosi* Morru Kiemfeld, MX.; JeugtuYwe Metsile, MX., and Irving & Taberehw, MX., Hew York ......................................................................................................... .............. Ptteomocosfatis oo the Kolar Gold Field, Sooth India Gtogr/y B. Ftreach, MX., MX* FS.CF. <C), OokvilU, Ont., Canada...................... 73 The Dust Diseases iq Great Britain .. A. IrGt'McLavghUn, MX.. F. London *3 Clearance of Radioactive Dust from the Human Lung Boy E. Albert, MX* Washington, D. C., end Lawrence C. Ameit, MX., Brooklyn___pp ^ The Antagonistic B&ogkal Action <rf Quarts and Potas&wa* Cafeecate G. W. H. Sckcfcrs, MX., DSc., and A. B. Dehhont, Sarastac Lake, N. Y................... 107 As Experimental Study of tl* Effects of Rare Metals on Animal Law Anthony B. DeUAonl, Sarat Lake, K, Y . 114 G. fV. R, Severs, UJ>^ DSa^Saruac Lake, K. Y. ''"'Tfae BWoi<al Actko of Cobaltic Oxide G; W. fi. HA, DJfr, Saranac lake, N. Y. m 122 Tlu BkJojkai Action cf FvtkuUte Cobalt 3/eta! G. ty. H. Stheptrs, AfA, Saranac takft, N. Y. 123 ^ Toe BieSapeal Action oi P*lkubte Ttzoffsta Hetal G. V. H. $cksp*. MA, DSc., Sataaac Lake. N. Y. in * The BtotogicaJ Action of Tungsten Catbtde and Carboo G. W. > $<US)., DStSaramc L*k*, *5. Y. 135 'The BtotoetoaJ Actios of Tcas Carbide and Cobalt 155 Tbe Pobseeaiy Dmfca&y Legtriatioc <rf South Africa G. W. H. ScUpm. MlX, DSey Saranac lake, N. Y. 14$ Evaluating Disability m Cbrepomtion for Pamarwxmoas Theodore C. Waters, Baltimore........ ........................................ .................................wji5? Tbe Radtg Problem in Deep-Level iSaaktg Dtmcon A. fioteloy, MAL, Salt Lake City,,,..................................................... Jg| > Otreat ProWesu* is Dost CctfnA to Mm3 Mtoes C. S, Gibton, M., Tmiomt, Ont, Canada................................. ........................ ..... 165 IT* Disability Fomd to Person Exposed to Certain BcryHimn Cotapoaode MerrittL Hardy,JU>.t Boston......... ................ ...................................,.....................152 v Tbe Effects of Inhaled TaJc-Mining Dost os tbe Homan Long G. W. H. Sehepen, AfA, AScv end T- M. Ditrksm, &t,, Saranac lake, N, Y......... 180 Pobaoeaxjf Disability as AskesSc Y'orken / Kenneth H'. Smith, JfA, New York......... ,................................................................ . l$k> Patoooiry Disability Associated with Caal Mining /..JF. G. ManKen, JHA, Washington, Pa............................................................ . 3&Z ,> "" Pathological Study of tbe Effects of Inhaled Gypsara Dost on Human Langs G. W. H. Sehefiers, MA, 2>Scv and T. M, Ourlan, M, Saranac Lake, N. Y.........2D? Tbe Dssoastratioo of Afansaom in Animal THsttea Dudley A. Irwin, MM* Pittsburgh................................................................................ 216 Experiences with the Cootro) ol S'lficcsis to a "Foundry lesUe //. Osmond, MDH Homestead pa....... ............................................................. 219 Prophylaxis and Treatment of Experimental SQicosu by Uean of Alumumas M. Dwrski, Sara/tac Lake. N. Y....t........................................... ............................... 224 < Experiences with the Control of Silicosis in tbe Ceramic IndoRzy D. A. Perry, MD, New Castk, Pa. 242  w'S"; ~.p. .**< ; **V -r^' y y \ /\ CONTENTS Some Experiences umh Silicosis Control in Cold Minins ?ace /. K. G&dm, MM., Beffeterre; Out, Canada..................................... .......................... Z45 Reaction of Chromium Compounds with Bed? Tissues and Their Constituents A. M. Bettjer, ScJ).; C. M, Damron., Ph.D.j J. H. Clark, PhD,, and V. Budec*, Pk.D., Baltimore......................................................................................... 253 Study of Surface Properties Qeartt Dust better D. Scheet, Pk.D., Saranac Lake, >3, Y,.......................................................... 25? Cytobjologieal Manifestations of the Surface Properties of Quartz C. IV, H. Sehefers. MM., DSe., Saranac Lake. N, V. 261 An Experimental Study of the Effects of Glass Wool on Animal Lungs GW. fi. Schepers, MD., DSe., end Anthony B. Delohant, Saranac Lake, N. Y........ 271 y4Tbe BidOffcal Action of G&ss Wool G. W. H. Schepers, MD., DSe., Saranac Lake, N. Y............,.................................... 275 Differential Susceptibility of Adroals to Bust W. M. Franks, MM., Toronto, Canaria......................................................................... 283 *"Aa Experimental Study of the Effects of Rare Earths on Animal Longs G. W, Jrl, Schepers, iT_Dv D.Se,; Anthony B. Delehant, end Andrew S. Redlin, Saranac Lake, T9. "Y........................................................................ 292 '"The Biological Action of Rare Earths G. W. H. Schepers, M.D., DSe., Saranac Lake, N< Y. I. The Experimental Pulmonary Histopaihdogy Produced by a Blend Having a Relatively High Oxide Content............................................................................. 296 II. The Experimental Pulmonary Hhtopathdogy Produced by a Blend Having a Relatively High Fluoride Content.............................................. -...................... 301 ` An Experimental Study of the Effects of Tak Dust on Animal Tissue C. IV. II. Schepers, MJ>., DSe., end T. M, Durban, MM., Samac Lake. N. Y.......... 312 The Biologies! Effects of Qfrined Gypsum Dust G. W. H. Schepers, M.T>,, D.Sc.; T. U, Durban, end A. B. Dtlahont, Saranac Lake, H. Y........................................ ........................ ................. 324 Effect of Inhaled Commercial Hydrous Calcium Sift'cate Dost on Animal Tissues G. W. H. Schepers, M.D., DSe.; T. M. Darken, MM., and A. B. Delahont, Saranac Lake, N. Y................................ ................. .................................... 543 Relationship of Particle Count, Weight, Shape, and Size of Air-Borne Dusts M. L. Roberts, MS., EM., Saranac Lake, N. Y............................................................ 356 Personal Impressions of Edward Livingsion Trudeau ai>d Edward R, Baldwin Hugh If. Kinghon, M.D., Saranac Lake, N. Y............................................................. 363 Memories of Leroy Upson Gardner Paul S. Richards, M.D., F.A.CS., Salt Lake City. 36? Anmal Report of the McIntyre Research Foundation for Year Ended Dec. 31. I9S4......... 375 Index ....................................................................... ............................................................ 3?y VKt CAStEV t. fcUCOSD, MC. An A*x, Mich. The scientific programs that eventuate in this publication have been scheduled and con trived to emphasize current contributions For the first time the McIntyre Research at high order. The key word of the Confer Foundation and The Saranac Laboratory ence has been "newness/' Newness in science unite in a shared enterprise: the Mclntyre- always implies an obligation to banish the Saranac Conference on Occupational Chest old when dearly it becomes demonstrated Disease. These two facilities arc bound to that the old holds no values save as markers gether in the common and high-minded dedi along the way to die fully acceptable ultimate. cation to acquire and disseminate precise-in formation on occupational diseases of tl chest and notably the dusty lung diseases. Essentially these two organizations are de voted to research in their single field of cover age. The much that already has been achieved chiefly reveals the inadequacy of full under standing of the pulmonary occupational diseases and thus piques the realization that the days of such research are not numbered. The scientific status of both organizations sponsoring this Conference is such that enor mous responsibility tests upon aU partici pants. What has been said in the many sessions unfailingly will touch industry. management, labor unions, compensation courts, physicians, educators throughout America and, even more, many other por tions of the world. This has imposed an earnest, zealous, cautious, and even prayer Recorded for publication April 4, 1955. ful appreach to the tasks in hand. Acting Conference Chairman, Consultant fa Industrial Medicine, Institute of Industrial HesJth, University of Michigan. Reed at the Mcfntyre-Saranac Conference 0" Occupational Chest Disease held at Saranac Lake, .V, y,f Feb. 7-9. J9S5, under the joint sponsorship of the McIntyre Research Foundation, of Toronto, and The Saranac Laboratory, of Saranac Lake. Not lightly stated, the purpose of this Conference and its subsequent publications comes to be the determination to add to the sum total of scientific rttainments sIvai even tually will bring all occupational diseases of the chest to praiseworthy control. 2 f 'tfisS***:* ^s.-*''**'-***1! A* --H A: / I ^Jhe Objective^ anA ^Achievements oj!th> lA]cAntyre $edearcfi 1foundation FRANCIS t. TRUDEAU. M.D, Sonec Lobe, N. T. McIntyre Research Foundation is a non profit corporation formed to carry on re search snvtstigatiaa in eoantction *wiih the prevention, mitigation, and eradication o! industrial diseases. As a primary concern, however, it has for many years actively pur sued a program seeking to prevent silicosis resulting from exposure to silica dust in occupations where men may be exposed to the hazard. The Foundation has pursued the latter objective, firstly, by encouraging the use of aluminum prophylaxis and therapy and, secondly, by sponsoring programs of intensified medical engineering control of dust and health hazards in industry. To understand more thoroughly the organ ization as it operates today, a brief sketch of tht historical background and the aims of the founders may be pertinent. The name McIntyre Research, Limited, was chosen when the first company lor the licensing of the aluminum patent was formed on Nov. 22,1939, to identify the effort with its sponsors, McIntyre Porcupine Mines, Limited- The co-inventors of the patents covering aluminum therapy were Dr. W. D, Robson and the late J, J, Denny, who were, respectively, plant physician and engineer to this mining company. In December, 1946, the shareholders of McIntyre Research, Limited, turned over its interest to McIntyre Research Foundation. This change was one in legal form only and in o way altered the work and objectives of its founders. Recorded for publication April d. I9S5. Thus the Foundation was formed with a charter membership of 10, and the interest of each member in the corporation was made nontransferable. The Directors of the Foundation, who con stituted the Committee of Management, were the surviving co-inventor of the patent, Dr. W. D. Robson, and those gentlemen who contributed to the success of the work accomplished up until the formation of the Foundation, namely, Messrs. J. P. BickeiJ, Balroer Neilly, R. J. Ennis, N. F. Parkinson, aftd Dcs. D, A, Irwin and J. W. G. Hussion* Messrs. Bickdl and Ennis passed away to 1951, and Mr. Balmer Neilly, although still a Member of the Foundation, has retired from active duty la it. The present officers and directors are zs follows: E, 2). Fox, President and Director--Director and Secretary, McIntyre Porcupine Mines, Limited, and President and Director, BeUeterre Quebec Mines, Limited. W, B, Dtx, Secretary-Treasurer and DirectonDirectorand Treasurer, McIntyre Porcupine Mines, limited; Director and President, Castle-Tretbewey Mines, Limited, aad Director, BeUeterre Quebec Mines, Limited. A. D. Campbell, Manager and Director--Manager, Lastif-TreSiewey Mines, Limited. Dr. J. W. G. Hannon, Medical Director and Director--of Washington, Pa. Dr. D. A. Irwin, Director--Chief Medical Officer, Aluminum Company of America. Dr. W, D. Robson, Medical Consultant and Director--of White Rock, B, C, Canada. Dr, F. Rohde, Medical Director for Mexio>-- ol Mexico, D. F.f Mexico. N. F. Parkinson, Director--Executive Director, Ontario Mining Association. M L, Uiquhart, Director--Manager, Meincyr* Porcupine Mures, limited. OBJECTIVES OF UeJNTYRE RESEARCH FOUNDATION The Foundation's research work initially was concerned with those chemical and physi cal processes which determine the incidence and rate of development of silicosis. Many re searches were earned out on these problems and included the effect of mine gases on the development of silicosis and studies of anti* dotal rocks, chemical and physical character istics of air-borne mine dusts, and the modi fying effect of admixtures of dust In as atmosphere that was primarily contaminated by silica. The experimental studies included as examination of not only the antidotal, or neutralizing, effect of admixed dust on the toxic properties of silica but also the opposite influence, L e., a study of dusts that are capable of accelerating the action of silica. Next followed clinical studies on the use of aluminum as a therapeutic means in silicotics with known disability. This necessi tated aa investigation of lung function in persons with advanced silicosis who were treated by ahimioum therapy in order to gauge accurately the effects of the aluminum. Later the scope o{ activities m the clinical research field was expanded to include the development of a field unit for the. study of pulmonary function. The object of this study was to develop an instrument which could be placed in the hands of the average plant physician and which would measure with reasonably soentific accuracy the pulmonary function of applicants for employment in as industry where atmospheric contaminants affect the lung function. In order to standardize methods of alumi num therapy, a studyofcoctroM production and dispersal of fine paniculate dusts and aluminum powder was embarked on. The chemical and physical characteristics of air borne dusts also required study, and some attention was given to the quantitative min eral retention of air-borne minerals m the lungs of miners. Side-issues in the program sponsored by the Foundation included observations on the relationship between stemo-vertebral diame ter of the chest aod pathological conditions in the chest More recently the Foundation has promoted pathological studies of the lungs by means of large lung sections accord ing to Gough's technique and the effects of temperature, air flow, air velocity and humidity Upon the production of dusts and powder. . The results of the Foundation's own re search and those of important international research in connection with silicosis and other pneumoconioses have been presented by the Foundation to licensees and others interested at its yearly Conferences. These scientific contributions are published and distributed as separates and as complete year ly Proceedings. (Jie (Contribution of the (Saranac laboratory to b^eSearcb on CUt 3>i leases E. 0. fox. Mi, T*rost*. Corda The Saranac Liberalry originated as a small unit which Dr, Edward Livingston Trudeau established in his homestead to 1885. Iq his autobiography Dr. Trudeau mentions that it was "the room opening from my little office, which was really the begin ning of The Saranac Laboratory for the Study of Tuberculosis " A few years later, in December, 2893, at a time when he was tit in a New York hotel, Df. Trudeau's home and laboratory were destroyed by fire. The Laboratory was continued, through die gen erosity of Mrs. Robert Hoe, in a small hastily built addition to the stable of Dr. Trudeau until the new fireproof laboratory building was completed. The new Laboratory, a gift of George C Cooper, of New York, who had been a former patient of Dr. Trudeau, was erected m \8&4 and became the first institu tion of this type in the United States in tended specifically for the study of tubercu losis. The library of the Laboratory was a gift from Horatio Garrett, of Baltimore. In 1924 Mr. Samuel Mather made a bequest for the establishment of tl Trudeau School, and since that time the Laboratory has been the headquarters of the School and has provided to nearly 1000 physicians basic training in die principles of tuberculosis and also during the past 20 years m the principles <A tive pneumoconioses and other occupational chest diseases. Through its seven previous sym posia on occupational chest diseases. The Saranac Laboratory has, Sit addition, disseffl- SubmSttfd for publication April 4, 1955. President. McIntyre Research Foundation. 4 inated a vast amount of original research data and served as a touchstone in this field of inquiry. After Dr. Trudeau's death, the Edward L. Trudeau Foundation was established as a memorial endowment fund mainly for the support of the Laboratoiy. Subsequently the Milbank Memorial Fund and the Black Me' modal Fuad each contributed $100,000 as a special endowment for research by the Lab oratory. The Laboratory has received gen erous research grants from industry and sup port from numerous charitably minded per** sons and in recent years has been entirely self-supporting. The Directors of the Saranac Laboratory have been, successively: Dr. Edward L. Trudeau, tbe founder, from 1894 to 191$. Dr. Edward R. Baldwin, frees 1915 to 1926. Dr. Leroy U. Gardner, from 1927 to ISW6. Dr. Aithur J. Vorwald. Sroro 1947 to \95S. Dr. Gerrit W. H. Scbejxrs, from 1954 to present. The Laboratory has made three majorcon tributions of great cultural value to this country. The first is the actual research which has been carried on during the past 60 years. The second is the teaching work done formally through the Trudeau School and the Saranac Symposia and informally to the many visitors and students from all parts of the world who have, from time to time, come to the laboratory. 'The third is the public service rendered all over the country through the lectures and demonstrations by the staff of the Laboratory at various con ferences of physicians, engineers, public bodies, and so forth. In addition, the labora tory has served as the clinical pathology cen- CONTRIBUTION OF SARANAC LABORATORY ter for the focal community and even for sur rounding towns. From 1803 until 1900 the Laboratory was a private nonprofit institu tion of Dr. Trudeau's. In 1900 it was incor porated with the State University at Albany, a legal status it has retained to the present time. The research work conducted by the Lab oratory has concerned itself with two major chapters. The first and the longest phase, and in a sense one that is still continuing, is the study of tuberculosis. Dr. Trudeau was one of the first physicians in this country to identify the tubercle bacilli in a patient's spu tum, a feat lie first accomplished in 1886. He subsequently proceeded to demonstrate the pathogenicity of the bacilli to experimental animals and to prove the pathogenic effect of the bodily secretions of tuberculous pa tients. The next phase of the study os tuber-' cufosis concerned the environmental influ ences on tuberculosis. Later, there followed a period of study on artificial immunity in animals. Next came a phase in which a va riety of substances were tried as therapeutic agents, ranging from hot air to creosote, iodoform, sulfureted hydrogen, hydrofluoric acid, essence of peppermint, and so forth. The experiments at the Laboratory proved mainly that the majority of these substances, while ineffective against the tuberculous dis ease, were capable of shortening the lives of the experimental animals. After this phase, the Laboratory concerned itself strongly with the problem of immune rcaclions and hyper sensitivity and participated actively in a search for a possible remedy against tubercuiosis. lt pioneered the possibility of an antitu* bcrculosis serum and, in the course of these studies, discovered the presence of viable tu bercle bacilli in imported T. R. tuberculin which was being sponsored in Europe as the result of the work of Koch. Through its sup port of the work of Dr. F. A. Levenc, one of the first workers at The Saranac Labora tory, the Laboratory pioneered the biochem ical study of the tubercle bacillus. This work was continued later at other centers, particularlv at the Kockefeller Foundation. The second major contribution to research pertains to the systematic investigation of the pneumoconioses. This phase of the work was truly initiated by Dr. Gardner and concerned itself both with animal experimentation and with the clinical study of industrial personnel who might be exposed to dust. With improvement in general health condi tions among the population of America, it became apparent that a major source of tuber culosis became known to reside in the indus trial population, specifically in those con cerned with dusty trades. Thus the industrial commitment of the Laboratory tended to be come its more important branch of study. As a result of this approach, the Labora tory proved through its research that the in halation of quartz dust was a major factor which adversely influenced the occurrence of tuberculosis in industry. Through a series of systematic studies on animals, the Laboratory contributed a tremendous body of infor mation concerning the pathogenesis of sili cosis and the distinction between silicosis and other dust diseases. At the same time, the Laboratory continued to pursue its study of the tubercutogenic propensities of indus trial dusts and demonstrated forcibly that the main phthisiogenic substance among these dusts remained the quartz particle. This work is still continuing. Antedating the publication of experiments by Canadian investigators dealing with the use of aluminum for the prevention of sili cosis, The Saranac Laboratory engaged in experimental work on this subject. Studies revealed that compounds of iron offered some promise as therapeutic agents for delaying or preventing the development of silicosis. After the report from Canada on the much more promising aluminum prophylaxis, the laboratory carried on a series of studies on the value of tiss agent, This investigation is still continuing. The Laboratory has maintained a field di vision in the Wisconsin-Minnesota area for many years and thus became intimately in volved in the problem of iron mining and the 5 FOX associated lung disease. This led to the estalfc. tishment of an industrial hygiene service and the evolution of a radiological division. The problems of coal miners in particular stimulated research into the field of emphy sema and heart disease. This led to the es tablishment of the physiology department. Next followed the extensive investigation into the very enigmatical issue of berylliosis, currently still under study. Dr. Gardner had the genius to recognize at this stage the need for inquiry into biochemical pathology, and therefore be created the department of biocbemis&y. This development of the Labora tory rendered possible the proper study of a new phase of the occupational dust diseases and prepared the way for investigations into carcinogenesis, with which the Laboratory is currently very much preoccupied. More recently the Laboratory has under taken the study of dusts other than mineral and at present has under way an inhalation experiment in which the dusting material is n plastic. Thus The Saranac Laboratory has striven to keep abreast of the problems of its times. I am told that its approach has ever been pragmatic. The staff is constantly inquiring into fundamental and even academic issues. 6 i: (Comparative *\Ja6cu(ar jf^atloiofyif Occupationai (Chest 2^idea6ed fa&Btaiy Ofaemrtien ceramic, workers), the more probably tuber culosis will be the terminal complication, aW. H. SCHEPSRS, M.D. Die , Sennet Ukt, K. Y. and the more likely will it be that the infec tive process will obscure any associated cardiovascular impairment Where the quartz ItfTS0T>UC7I0N content of environmental dust is low, as I It Is probably common knowledge that in* among coal miners, there is a greater tend dostrial 'employees who have been exposed ency to cardiac deaths, and there are fewer to dusts oi various kinds have in the past tuberculous .terminations. But numerous manifested a tendency to die either of a tu anomalous results may be found where there berculous complication of a concomitant is no apparent inverted relationship between pneumoconiosis or of cor pulmonale^ Such the two -diseases. persons raay, of course also die of any of the There is no necessary relationship between mtercurrent nonoccupation&l causes. The the degree ofdemonstrable fibrosis associated underlying occupational chest disease may with pulmonary dust deposition and the also terminate life through other mechanisms, prevalence of tuberculosis or cor pulmonale such as esophageal, bronchial, or arterial as terminal events. Thus there may be a very erosions by silicotic lymph nodes, with ensu marked degree of pulmonary collagenosis ing pulmonary or mediastinal gangrene. The associated with asbestosis without a mate latter category of mechanisms tends, how rially enhanced incidence of tuberculosis, ever, to be in the minority. It must be em Cor pulmonale, on the contrary, is commonly phasized, too, that no precise information found in association with asbestosis, but its exists today concerning the relative role of severity does not necessarily parallel the ex cor pulmonale as the causative factor of tent of the interstitial fibrosis. Many cases death in comparison with tuberculosis. This of advanced asbestosis may escape a cardiac . may be because It takes a greater measure complication entirely. * of clinical diagnostic ability to diagnose cor Silicosis likewise is vicarious in its effects pulmonale, and objective findings are less on the vascular system. Although a preva easily identified post mortem. Many cases lence of tuberculosis in excess of 75% was of tuberculosis may even die through heart once a predictable accompaniment of silicosis failure of the cor pulmonale type. Tubercu in South Africa, while tuberculosis may still losis statistics, on the other hand, are fairly be found in 21% of first-stage silicotks at well knows, and the mechanisms of death death, and whereas it features as the cause fairly well understood. of death in more than 50% of second and It is apparent also that the relative in third stages, the relationship of cor pulmonale cidence of cor pulmonale in relation to tuber to the equivalent grades of silicosis does not culosis varies markedly from industry to follow the same logical pattern. Indeed, it industry. The higher the quartz content of . is. not uncommon nowadays to find miners inhaled dust fe. g,, cases of gold miners; with advanced silicosis who have no demon Submitted (or publication April A, 1955. Director, The Saranac Laboratory. strable abnormality of the vascular system whatsoever. There may be a simple anatomi- 7 / SCHEPBJRS cal explanation for this. Ia these cases of tuiajmpUcated silicosis, the fibrofk process is usually almost completely confined to the pulmonary parenchymal Jymph nodes/afed in these positions it cannot exert any deleterious influence of any consequence on the blood vessels of the lung. With the steady reduction in tuberculosis mortality among industrial workers all over the world, cor pulmonale has become a rela tively more important cause of death. This is an unexpected finding which needs fuller explanation. It is likely, of course, that its higher present-day prevalence is partly il lusory and explicable in terms of better diag noses, electrocardiography, and improved radiographic techniques, rendering possible recognition at a much earlier stage arid with greater certainty. The earlier preoccupation of physicians with the socially exceedingly dangerous tuberculous complication, and the overweening importance of the latter, per haps obscured an even greater earlier prev alence of cor pulmonale. The net present result, however, Is that cor pulmonale is the more important sequel to be on one's guard against Id dealisg with employees who have been exposed to environmental respiratory hazards for protracted periods. So far these diseases have been referred to primarily as causes of death. All the pre ceding remarks apply tnutaHs mutandis and with almost equal emphasis to tuberculosis and cor pulmonale as causes of disability, with the proviso, however, that additional causes of functional impairment may coexist, precede, or complicate these conditions with out necessarily being capable of causing death directly. Thus one has to think here of conditions, such as emphysema, chronic bronchitis or bronchiectasis, and diffuse fibrosis, which may help to impair the work ing capacity of the dust-injured employee though but seldom capable of causing death directly. In most Instances where the latter three types of complications are present an any sufficiently severe degree, they lead to death through the mechanism of right heart failure. The riddle of cor pulmonale can only be solved when once we have discovered its precise mechanism of causation in relation to the occupational dust diseases. From the medicolegal point of view, it may be of crucial importance to know whether the cor pulmonale is Invariably sequential to a recog nized pneumoconiosis or whether it may arise through primary injury of lung ves sels by the dust. By definition, of course, the cor pulmonale is invariably sequential to impairment of the pulmonary circulation, and the cardiac result may be achieved either through altered physiological factors or by means of direct anatomical damage either as a sequel of the specific pneuraoconlotie reaction or through direct action of the dust on the blood vessels. The Indirect physiological mechanisms whereby the chronic occupational lung dis eases can cause heart failure are raultiphastc but fairly well understood already. Emphy sema may, for instance, mechanically obstruct the circulation of blood through the alveolar capillary network, which effect the right ventricle would attempt to overcome by a process of hypertrophy. Any series of pul monary infectious of long duration and suf ficient severity, such as may ensue in any chronic pneumoconiosis, may, through the dual effect of znyocardkl impairment (cloudy swelling) and the increased cardiac output related to the higher metabolism of the fever state, lead to congestive failure. At the same time the increased oxygen demand created by fever would tend to increase the respiratory effort in the partially anoxemlc patient. This would create a vitious circle. At the same time any superimposed pneu monic process would further encroach on an impaired pulmonary vascular bed and render futile much of the perfusing function of the pulmonary circulation, inasmuch as such perfusion would now be to aonventilated areas. The bronchial or bronchiolar obstruc tion attendant on many respiratory tract inflammatory states would further aggravate the ventilatory insufficiency. The main func tional mechanism of genesis of cor pulmonale in the occupational chest diseases appears, $ COMPARATIVE VASCVl-AR PATHOLOGY however, to be anoxia. Physiologists such as Euler and Liljestnuid1 and also Fishman, MeGement, Himmelsteia, and Command* have conclusively demonstrated that anoxia may directly enhance pulmonary arterial elucidate the nature of the latter morpho logical factor, its nature, localization and distribution, prevalence and relative signifi cance ra the different occupational chest diseases at various stages, prompted the vasomotor tone, with resultant increase in present inquiry and has yielded the results pulmonary pressure. This mechanism may to be presented. be augmented by associated polycythemia, hypervolemia, and increased cardiac output. Anoxia may further directly impair the ef The study has been conducted on both the human autopsy and biopsy material and the experimental animals constituting the collec ficiency of the cardiac muscle, and when this factor is combined with the enforced need to maintain a greatly increased pul tion of The Saranac Laboratory. In the pres ent account only reference to human lesions will be made. Though the range of material monary arterial pressure, congestive cardiac available for analysis is both unique and failure ensues. Command' and McMichael * extensive, no pretense can be made at this have adequately explained these terminal stage that more than the fringes of the prob mechanisms. As there is no intrinsic cardiac lem have been touched. Only a preliminary disease, it is important to realize that the whole process remains reversible, while the . pulmonary lesions are yet amenable to treat ment Once the lung disease has advanced account will be presented, giving prominence to some of the fundamental principles al ready uncovered and illustrating certain of the more spectacular lesions. While empha too far, sot erven bed rest can materially sis will be given to these abnormal vascular ameliorate the cardiac failure, which is not features, it must be pointed out that it is primarily dependent on exertion, as in val neither the intention nor within the range vular, coronary, arteriosclerotic, and hy of possibility at the present stage of the pertensive heart disease. Such men only too often tend, therefore, to work until shortly before death, and conventional cardiac sup portive measures prove of no value. inquiry to evaluate the relative severity and to quantitate the multiplicity of the lesions Id be enumerated. And while reference vriD be made to the comparative vascular path In many occupational chest conditions in ology of die different pneumoconioses, it Is which cor pulmonale has supervened, the by no means the objective of this paper to aforementioned functional mechanisms can, however, not be satisfactorily demonstrated. Neither emphysema nor pulmonary fibrosis may be present in a quantitatively significant degree. Physiologists have toyed with the concept of thickened alveolar membranes or have sought to adduce proof of increased resistance to gas exchange across the alveolar membrane. There is some apparent success in this direction, so that we have a further mecltanism whereby cor pulmonale may be provoked through anoxemia. Histological confirmation of such damaged membranes requires further elaboration. The physiolo gists have also drawn attention to the factor of impaired oxygen transport and inequalities of perfusion which presuppose some defi present a final determination of the manner or degree in which the different dusts affect the vascular systems of the lungs. Attention wifi rather be drawn to the levels of vascu lar arborization at which significant func tional impairment may be engendered through morphological change. Logically, too, this account should include in detail the major well-known lesions of the pulmonary vascular system, such as pulmo nary artery aneurysm with erosion, hemopty sis, rupture or pulmonary artery thrombosis with infarction or dissemination of emboli. These pathological manifestations are well known already, and it must suffice for the present to draw attention to the fact tliat they ciency of the pulmonary circulation, either occur in association with the various pneu functional or anatomical. An attempt to moconioses. 9 SCHBPMRS LE5J0KS OF TffE ALVEOLA* WALL It has beat possible to deogjastrate ob literation of the capillary network over esc* that the; functional efficiency of the alveolar wall must be seriously disturbed through the interposition of the collagenous sheath be tensive areas of alveolar walls In many in tween the alveolar space and the blood cells. stances (Figs. 1-3)- The commonest cause This morphological feature would serve to of this disorder in asbestos-, quarts-, cris- explain the increased gaseous transfer gradi tobalite-, and talc-exposed workers is the ents observed in some of the occupational abundant deposition of collagen within the chest diseases. wall (Fig. IB). The collagen fibers make Another mechanism whereby the alveolar their appearance in the central mural plane wall capillaries may be occluded is seen in intervening between capillary plexuses facing adjacent alveolar spaces. This observation vo iuett is interesting insofar as h duddaAes quartz rock, coal, and graphite miners. In such cases carbon-laden koniophore cells infiltrate into the aVveokr membrane and by the fundamental anatomy of the alveolar . accumulating here in great numbers effec wall whose contained capillary networks are tively displace the capillaries (Fig. \A). thus revealed to be of a dual nature in many Once more it should be stipulated, however, localities, each alveolus having a generous that a possible additional factor in achiev supply of capillaries of its own. By the ing this result may be through the occlusion abundant thickening of the eoUagen sheet, of arterioles supplying such lung areas, these capillary plexuses art apparently pried In talc workers and persons affected by apart. However, there apparently is more the sarcoid-like granulomata ascribed to than mere quantitative deposition of col beryllium, and also as a result of the initia lagen to account tor the disappearance of tion of amorphous ultramicroscopic siKceotu the capillaries as the. latte; ace frequently particles, the alveolar waJk may be naricedly seen to survive and overlie abundant masses infiltrated by cells, mainly macrophages but (Fig, 2A). It is possible that m such cases also lymphocytes, plasma cells, giant cells, the capillaries have atrophied because of and fibrocytes, The abundant presence of vaseafet ocriasiun m an arteriole in dose such cells efiectively strangles all capillaries proximity. This seems warranted when one adjacent to them (Fig. 2A). takes cognizance of the fact that capillaries A final mechanism whereby alveolar walls frequently survive excellently in spite of the are thickened and in which capillaries a abundant presence of a central mural col implicated may be seen in iron miners, lagenous mass. The latter condition has welders and asbestos and foundry workers been sees not only in cases of asbestosis but more particularly. In such cases multiple also in association with quartz, iron, and diatomaceous-earth pulmonary reactions. The commoner mechanism whereby capil layers of collagen and capillaries may be present The capillary plexuses may alter nate with collagen layers or may surround laries are obliterated results from a super them. There may even be pure multilayered ficial deposition ot collagen between the sep proliferation of capillaries (Fig. SB), It is tal cell layers and the endothelial cells of quite apparent that, in spite of the addition the capillaries (Fig. 2B). Incidentally, the of such excessive vascular components, only interposition of this layer of collagen leaves the most superficial capillary plexuses are no doubt whatsoever concerning the separate exposed directly to the air of the alveoli. existence of a septal cellular membrane. The The deeper layers not only become redun capillaries become embraced within such dant but also may constitute a functionally collagenous sheaths and are seen to be con disadvantageous vascular by-pass. This hy- siderably namowed, and their . continuity peremic condition is then the* very reverse throughout the alveolar walls becomes finally of the ischemia previously described but may interrupted. Even before the capillaries com equally be a cause of cardiorespiratory func mence thus to atrophy, it U quite apparent tional impairment. 20 COMPARATIVE VASCULAR PATHOLOGY SHALL BLOOD VESSEL DAMAGE The lesioos of the smaller blood vessels coocens changes of the endothelium and rndma, alteration of the muscular coats, and perivascular reactions. Intimal lesions have been most commonly seen is the lungs of deceased persons ex posed to quartz, asbestos, tak, iron, and beryllium salts (Fig.4/4). The quartz type of reaction tends to take the form of a centripetal deposition of con centric collagen bundles, and the advancing broadened mtima gradually seals off the vascular lumen. The resultant effect may not be very dissimilar to a mature silicotic nodule, except that the residua of the lamina elastica may be demonstrable by appropriate staining; techniques. The endothelial reaction in iron miners' and foundry workBrs' lungs may appear as nodular excrescences copiously charged with metallic particles. These swellings may ef fectively obliterate the lumen. In the asbestos, talc, and beryllium cases there may be a fibrocelluiar proliferation of the intimal zone without any obvious deposition of foreign bodies, though the latter may be present in great numbers around the blood vessels. Oc casionally asbestos and tremolite bodies may, however, be seen within the ititima, and iron staining may bring out marked focal pre valence of such elements, especially is talc workers (Fig, Zfi). Both in talc and in asbestos workers there is a greater tendency for veins to be similarly affected. Completely occluded venules are frequently seen within larger masses of fibrosis, their lumina being sealed off by abundant intimal tissue com posed of a loose web of collagen with Inter spersed cells (Fig. JOB). Unless such areas are stained by collagen or elastic tissue methods, these features may be missed en tirely, as the destroyed vessels ultimately merge completely with the surrounding scar tissue. Damage to the muscular coats is most commonly seen in association with asbestos and tak exposures. It tends to take the form of a focus of irregular fibroccllular reaction which invades and disrupts the continuity of the musck streets (Fig. 45), Asbestos or tremolite bodies may be demonstrable witliin the lesion. The whole mass may bulge prominently into the vascular lumen, almost to the degree of partially occluding it This effect may be aggravated by s measure of intimal proliferation opposite the nodule, and thrombi tend to form at such rites. Perivascular reactions staod out, However, as the most important features of the occupa tional dust diseases. They may be present around the smaller vessels, with or without any narrowing of the lumen. In most cases they commence as macrophage or lympho cytic accumulations in the perivascular lym phatics (Fig. 5). Deposits of this nature are probably least common in the frankly silicotic rases and most prevalent in association with asbestos, talc, coal, -and iron exposures. The reaction occurs cither as a cellular deposit or in the form of a collagenous sheath (Figs. 6A and 1 \A). The tak and gypsum perivascular lesions are probably the most characteristically cellu lar examples (Fig. 65). In instances of virtually pure taic exposure, abundant macro phage deposits accumulate around the smaller vessels and generally do not affect the vas cular lumen materially. Provided that quartz has not been inhaled along with the talc or gypsum in any significant amount and pro vided that the tremolite and anthophylltte content of the tak as low, virtually no col lagen is found in these masses, and the en circled blood vessel may show no material adventitial reaction or change in caliber. Cellular deposits are also characteristic of graphite, coal, and iron miners, with the qualification that these cells are now heavily laden with the appropriate foreign substance (carbon, coal, or iron). The essential lesion of coal miners' pneumoconiosis and of tiderosis is such a perivascular koniophore de posit, and this feet emphasizes the error many radiologists fell into when they seek Jo differentiate between vascular shadows and nodules m these diseases. It is simply not possible to make such a distinction (Fig. 7A). IS SCHBPER5 The perivascular coal lesion may usually wails- In a case where the main exposure be demonstrated in every stage of its evoW was to cristobalite and in another where the lion in the average case. It commences as causative agent was asbestos, considerable a dominantly cellular limited deposit around irregular thickening of the mtimal layer smaller blood vessels, mainly arteries. By the successive addition of new dust-laden cells, the mass grows progressively until it has the appearance of a stellate nodule. The more quartz there may be, the greater the abundance of collagen fibers which axe de posited among these cells and the stronger tbe tendency for their deposition in the form of concentric whorls. The tendency toward stenosis and virtual occlusion of the blood vessel is enhanced by the presence of quartz along with the coal or iron, but even when the free silica content of such lungs is vir tually insignificant, marked stricturing of the blood vessels contained within the pig mented masses commonly occurs. Perhaps the sole of these changes has in the past been somewhat overlooked as a cause of pulmo nary disability and ultimate cor pulmonale in anthracotics and siderodcs. In ssbesioris, tbe earlier perivascular re action tends to be cellular and 1$ replaced later by a loose collagenous plexus. Asbestos bodies may frequently be seen both in the cellular phase (Fig. &A) and also later when the fibrous collar commences*to form, the bodies remaining trapped among the collagen bundles. Within this mass the trapped blood vessel either may show no change in caliber could be demonstrated in some medium- sized vessels without any simultaneous dam age to the elastic laminae but with some fatty infiltration of the muscular coat (Fig. 9A). There was, however, considerable peri arterial fibrosis in these as well. More generally the lesions of the mtimal coat are atheromatous plaques, and these occur in the main pulmonary arteries ox their primary branches. However, one case of an non foundry worker was found in which atheroma could be traced to the fourth and fifth scries of vascular ramifications, Ho significant atheroma was demonstrable in this case in the aorta or systemic vessels. A rather spectacular injury sustained by thepulmonary arteries of intermediate caliber may sometimes be seen and takes tbe form of segmental collagenous infillration in the muscular coat whose individual bundles may be seen to be separated by intervening fibrous layers (Fig. 9B). I&stances of such change have been seen in association with both silicosis and asbestos)*, Neither pigment nor asbestos bodies could be demonstrated within these degenerative vascular segments, but this does not exclude their being present, At such segments the vascular walls may be considerably thickened. and form or may be markedly narrowed and distorted. Tl concurrent presence of some quartz in the lung tissue markedly en hances the latter tendency. Perivascular changes prdvoked bycrisfobalite, as in diatomaceous-eariK disease; tend to be in the nature of a diffuse, irregu larly collagenous character, with many cellu lar elements interspersed.among the fibers. The perivascular reactive zone shades off gradually Into the more distant lesions. Similar changes have been seen In the veins is asbestos)s but not in silicosis. Changes in the vascular adventitia are to be expected, as the specific dust reactions are grouped around the Wood vessels. These changes are most frequently observed in asbestos* and diatomaceous-earth disease and may include some damage to the external elastic lamina, especially In the case of the veins coursing through interlobular septa. Such changes are also quite common in cases damage to asteriks and veins Blood vessels which may seem perfectly normal to.naked eye inspection may never theless present a variety of pathological fea tures on rttiQroscopie examination of their of silicosis or siderosis where there has been a significant degree of associated infection. The essential nodule of coal miners' anthracosilicosis is also a similar lesion, though the abundance of the perivascular carbon pigment may obscure the associated col- n  *:**,. COMPARATIVE VASCULAR PATHOLOGY iageao&is unless special staining is resorted to the vascular system, They are, in a seise, to. The central veseel either may he markedly pericapiUary lesiona, which accounts for their constricted or may show oo material nar diffuse character. rowing of its lames- Arteries tend to show The relationship between the silicotic nod the former type of reaction and veins the ule and the vascular system is the most inter latter, though this is not an inflexible rule. esting to explore. It has been fairly well As interests^ feature observed more par established by the work of Simson, Straclian, ticularly in anthracosis and siderosss con and Irvine * that the classical silicotic nodule cerns the attempted effective recasaliaarion develops within the pulmonary lymph nodes of partially occluded blood vessels through in man. This accounts for its characteristic i the enlargement of one or more of the vasa location and its discrete or focal character in ' vasorum (Fig. 75). Whether any signifi the average case of moderate exposure to cant measure of collateral circulation may quarts particles. The distribution of these thus be e&t^hhd remains in some doubt, lymph deposits has been fairly well defined though lietcwV* researches have given by Miller,* They tend to occupy the points of strong support to the fact that the bronchial bifurcation or ramification of the pulmonary | .-arterial -system nzy materially supplement arteries and also follow the venous system ^'iusd. sustainra^flefeerive pulmonary arterial:; atong interlobular, septa toward the pleura system. It is' raitijte that such a coilateraf ` Ift th*is1 se; ns*e",' t-h, ere*fore, w*h"ile .t.h..e....s...il.i.c..o...t.ic calculation ma&:adequately deraoz&trated' nodules not perivascular, they are at only through injection techniques and that least paravascular in topographic disposition. the sites oft inosculation hre rapidly obliter Lymph nodes are supplied by arterial twigs ated, HoWever, an the examples identified from adjacent arteries, and it would be sur in The Saranac Laboratory series, it seems prising, therefore, to find silicotic nodules that the communication between the pul which have not at least some semblance of monary and the bronchial arterial systems a relationship to the vascular system. The is definitely via the vasa vasorum. mature hyalinized silicotic nodules appear to be completely avascular, to be true, but the &ELATIONSSIP BETWEEN VASCULA5 LESIONS immature nodule almost always has a small AND SPECIFIC DUSE NODULES arteriole leading to it Sometimes this vessel The crucial medicolegal issue which ema Is eccentric {Fig. 12A), and at other times nates from the foregoing demonstration of a it is central in relation to the whorls of col variety of pulmonary vascular lesions in lagen {Fig. US), What happens to this persons who have been exposed to different vessel ? When* sufficient numbers of nodule occupational hazards concerns sot only the sections are prepared by means of elastic relationship of such lesions to the dust par- stains, it may be possible to demonstrate the rides whfoK are demonstrable within them remains of such vessels often deeply buried but N^re* particularly their relationship to within the mass of collagen (Fig. 225). The tlw.p^ogubmook dust reaction. elastic lamina survives the collagen change The majority of the occupational dost and leaves a telltale ring pattern. diseases are characterized by the presence of , This discovery has dual significance. In nodules in die luhgs. Silicosis is the classical the first instance, it reveals that the very J and extreme example, and asbestosls the least creation of*i!icoticfnodules may be dependent conformer. The nodules of sidcrosis, anihra- on thq-existence of .a system of nutrient ar- ciatcd with befyllffiro exposures, 'thoi^h^4 points to^he iafJ that the maturation of joeal^ed to thealvjlalar walls, are essentially ; sifeotk r<Sujcs1^ads to the interruption of .per)arterioIar?*Shaver's disease and diato- *.the xontirush *of;small4r arterioles, These Imaceous-earth discase are less readily related* ' may allrtrc en<b:arterie$ destined to the lymph n >' a SCHEPERS nodes in which the silicotic nodule develops, 1CM). Such capillary infiltration into the so that final occlusion of the vessel may have area of pigment deposition or fibrocellular no material effect on the pulmonary circula reaction is entirely lacking in amhracosis, tion as a whole. On the other hand, if the siderosis, berylliosis, and talcosls. In the shut-off vessels were also required to perfuse areas of reaction to gypsum, capillary pro areas of lung tissue beyond the site at which liferation may be markedly enhanced. the nodules form, their obstruction by the Id the pleura, too, such distinctions are silicotic nodule would be reflected in regional usually demonstrable, The silicotic pleura impairment of lung function, whose total tends to be avascular, and this tends also to effect would ultimately begin to influence the be the state of affairs in siderosis, berylliosis, efficiency of the lung as a whole when suffi and anthracosis. Is asbestosis, ulcosis, and cient numbers of mature nodules have been the gypsum lung, the pleura may be focsUiy formed. The foregoing features have been or diffusely thickened through the addition seen in both silicons and sideroriheosis. of a layer of collagen-infiltrated tissue be In asbestosis we find an entirely dissimilar tween the lamina elastics and the meso- state of affairs. The predilection of the as- thelium. This zone is richly permeated by bestotk focus is paravenous {Fig. iSA). vascular and lymphatic capillaries, and within The fibtotit area n seldom spherical as m it asbestos and tremohte bodies may often silicosis, though it may, be circular is cross be demonstrated. section- More generally it presents as an irregular mass adjacent and adherent to the PULMONARY ARTERIES venous adventitia and..composed partly of Reference has already been made to ather cells and partly o megohriy ahgned col oma as a relatively common finding in the lagen and elastic bundles with asbestos fibers and bodies among these. The wall of the vein may or may not be materially affected by the presence of the asbestotic reaction. In this respect once more asbestoria differs from fatima of pulmonary arteries and their pri mary branches, especially when chronic cos pulmonale is present (Fig. 15^4). Such atheroma relatively seldom progresses to thrombosis or erosion, but aneurysmal dis silicosis, for when a silicotic nodule comes to tentions are sot uncommon in silicosis. In lie against a large blood vessel the muscular component of the vessel closest to the nodule becomes considerably thickened and distorted through the deposition of collage* bundles . among the muscle fibers (Fig. 13). all the occupational pulmonary dust diseases, marked distention of the pulmonary arteries and their primary and even secondary branches may be a prominent feature. The vessels may be doubled and even trebled in * Asbestotic fibrocellular masses are eom- caliber. Such changes are, however, com monly disposed around extensive sections of monest in berylliosis, silicosis, asbestosis, and . veins or arteries. The presence of the en talcosis. This condition is rare in uncompli circling cicatrical mass distorts and narrows the vessel (Fig. 11A), though not invariably, . and it is often surprising to see how little the vessels imbedded within extensive masses of asbestotic granulation may be disturbed. These variations may account is some meas ure for the lack of correlation between the degree of disability and the extent of pul monary reaction seen in asbestoses from the same or different industries. . Asbestotic tUiu* differs further in a vascu lar sense from the siNcotrc reaettohjin pos'sessing a generous capillary supply (Fig. J4, cated siderosis. Stenosis distortion and fixation of the pul monary vessels through hilat fibrotic masses or by the presence of enlarged hilar nodes is to be seen most commonly in silicosis, particularly where there has been some asso ciated infection (Fig. 14A). It is ait uncom mon feature in uncomplicated siderosU, anthracosis, or asbestosis and has not been present in the beryllium, scries available for examination. Opposite silicotic nodules these larger ves sels often show some measure of mural COMPARATIVE VASCULAR PATHOLOGY thickening, with or without collagenous greater the more frankly tuberculous tire <Ftg. US) and iotimal atheroma (Fig*. lesion happens to be. These features may 14A sad 155), This state of affairs has not explain the relative paucity of frank and been sees la the other occupational dust dis massive hemoptysis in tuberculosilicosis as eases of the lung. compared with tuberculosis itself. The range of abnormalities of the larger Blood vessels may also become trapped, pulmonary vessels is therefore relatively degenerated, and occluded by two additional limited as compared with the multiplicity of mechanisms In the presence of added juice- changes demonstrable in the smaller vessels. tion. Where tuberculosis manifests itsdi as It is indeed apparent that the brunt of patho a transient pneumonic process is a silicotic, logical stress falls on the least components. the vessels within the inflamed area acquire ' of the vascular system. a dense fibroceUular sheath during the pro . INFECTION AND VASCUtAB A*N0B*AL1T!E ; Theaddition of tuberculosis to the silicotic l process ha* a markedly deleterious effect op ' tlit pttWswmaTy Wood vessels. Tuberculosis (per sffcdoes not necessarily affect the vascular j:etogns, thougb,whcn sufficiently advanced, * the fiferotic process izay obliterate blood ves- cess of resolution or organization, and the proliferation of these cells indicates clearly ttet they derive some of their stimulus from the presence of quart* in the perivascular lymphatics. A final manner in which such vessels be come affected is discernible in the paren chymal tissue whkh intervenes between ad seIs. This, however, seldom leads to a cor jacent tuberculosilicotic masses. Here the pulmonale (Gardner1). Even in tutcrculo| silicosis, cor pulmonak may be a kss commoo i. accompaniment of advanced disease than, in arteries in particular are seen to acquire thick fibrocellular cuffs within whkh charac teristic taberculosiboAic tissue reactions may * comparable degrees, oi nomnfective lesions, though not infrequently the most advanced stages of right heart involvement are seen in take place, thus indicating the presence of both the dust and the infective components. Such vessels show a marked tendency to connection with the combined disease. The endarteritis obliterans. former state is somewhat surprising in viev? The infective processes just described in of the extensive loss of vascular bed which connection with silicosis are demonstrable in accompanies the infective process. The tuber- siderosiiicosis and anthtacnsUkosis as well culosilicotic lesion, in particular, is charac but tend to be markedly modified by the terized by its virtually complete avascularity. presence of the specific iron or carbon de The maimer in which Wood vessels may posits. la the case of both astbracosilicosis become affected in tuberculosilkosis varies. and siderotis, the carbon and the iron appear, Where the process is tuberculosilicotic from respectively, to enhasvee the tendency to vas ;the starts the vessels are slowly involved by cular damage where there is associated tufeer- the peripheral expansion of the, lesion. It culosis. When tuberculosis supervenes in . ' firstbecomes adherent to the infected nodule, either relatively* pure siderosis or anthra- arefsubsequently dust-laden phagocytes and cosis, the presence oi the iron or the carbon ' fibrocytea tndrefe the vessel while its walls ; ha* the opposite influence In that these sub undergo degenerative changes. Through stances tead to retard vascular damage. imlfnal proliferation the lumen is thereafter Asbestosis is but seldom complicated by . occluded. ' tuberculosis, and when the latter is present, Siifctiar changes are seen in proximity* to there appears to be no specific tendency to ' k tbei$ubv& cavities whose walls may con- added vascular damage. More commonly ' /tain m^t^T^egenerated and occluded wss4ls. the infective agent in asbestosis is in the Oca^ipnay^rhowevef, a blood vessel may be nature q ;a poaspedfic bacterial broncho- 'Seep ^JiTVJve-within.one of th* sejHa of a. pnenmofiiflv .The repeated recurrence of such ; muItilocu&l cavity, cn^ this tendency is the: inflammatory episodes has the effect of trap- *'V. . -t is SCHBPERS piog large number? of asbestos fibers within stenosed, becoming sporadically occluded as organizing tissue and thus rapidty to extend terminal regional phenomena. Perhaps the the asbestotic granulation reaction. No spe mechanism in the lungs is comparable with cific damage is caused to blood vessels in this systeauc pattern of behavior, so that this process, and one gains the impression partial narrowing of lung blood vessels and rather that they are less disturbed in such segmental injury to their walls may have a areas than in the more chronic primary as more markedly enhanced effect in raising the bestotic process. Similar remarks apply to pulmonary artery pressure than when these takasis. though the tendency for a quarts vessels are completely occluded in the pneu- component to further complicate the matter mocomotte process. The relative ischemia at by forming perivascular fibrottc deposits is points distal to such narrowings is bound to relatively strong here. When quartz is influence markedly the capacity of the lung present in moderate amounts, the resultant to oxygenate the blood, and the ensuing postinfective.lesion may initially be a col- anoxia and resultant pulmonary hypertension tagenized granulation tissue which is well will be proportionately greater H there are permeated by capillaries. at the same time other associated causes of anoxia, such as bronchoapasra and emphy REUkTJONSHtF BETWEEN VASC0LA8 CHANGES sema. This will tend to lead to a vicious I AHt> COR EULyONALE cycle, for progressive increase in pulmonary The foregoing account of the variety of artery tension is not likely to improve circu vascular changes to be encountered in asso lation through distorted, narrowed, fixed, or ciation with some of the occupational pui spastic arteries, arterioles, and capillaries. snenary dust diseases must perforce incline Whether the vascular damage per sc (i. e., in one to the cooclusioa that the magnitude of the absence of such associated causes of the blood-vessel disease cocountered in the anoxia) would be sufficient to provoke pul lung may play some part in the genesis of or monary hypertension is not yet proved at pulmonale. In theory, one could imagine the this stage, but the anatomical basis for such right heart laboring against peripheral ob a possibility does at least exist, and in terms struction in the pulmonary circuit However, of hydrodynamics it ought to be possible, the principle involved is more than one of mere mechanics. By analogy, for Instance, sumuaiv the ventricle does not hypertrophy because The lungs of persons who have been ade a patient has had his legs or even all his extremities amputated. Even inthe presence of multiple peripheral and organ infarction quately exposed to industrial dusts, including quartz, iron, coal, tak, gypsum, diatomaceous / earth, beryllium compounds, and asbestos, J in atheromatous disease, winch presupposes either singly or m combination, show a a markedly reduced systemic vascular bed, diversity of lesions of the blood vessels whose systemic hypertension docs not necessarily prevalence and extent vary according to the develop. Similarly, pulmonary hypertension Is often conspicuous by its absence In ad vanced fibroid phthisis in which a majority nature of the foreign substances deposited in the lungs, their quantity, and associated infection. of hang blood vessels may be sealed off. The most marked effects are on the smaller No doubt many subtle physiological mech vessels and comprise cellular amd coHagenrras anisms are brought into action before the lesions of the capillaries in the alveolar walls, right ventricle will tend to hypertrophy in damage to the intima, muscular coats, and response to rising pulmonary tension. In adventitia of the arterioles and venules, and the case of left ventricular hypertrophy asso- . perivascular deposits of pttrments, fibrocytes. elated with systemic hypertension, there are , .'and.'rnacrophages with variable degrees of functional as well as organic peripheral vas- associated fibrosis. The effect on these small ailar changes and vessels are only partly vessel? may be to occlude, stenose, and distort U' - r f 'COMPARATIVE VASCULAR PATHOLOGY and to create inefficient vascular short circuits. ; larger pulmonary vessels may also show damage, ranging from intimal atheroma to medial segmental hypertrophy and collagen degeneration, deatria] stenosis, and aneu rysmal distention. Such vessels may become - fi. SUbsoo, F. W.; Straehan, A S* and Irvine, L. G.: Silicosis a South Africa, Proc. Transvaal Mint M. OS. A, Spec. Supp, t9. ?. Miller, W, S.: The Lung, Springfield, III, Charles C Thomas, Publisher, 1927. 8. Gardner, I- U.r Silicosis and Related Con ditions, 3- Indust Hyg. & Toxieoi 1937. eroded and rupture. DISCUSSION In silicosis, the vascular damage is an Da. P. G. Bovaio: Dr. Scbeprn* discussion waa added lesion over and above the specific col extremely interesting and new, I would like to ask lagenous nodules, which latter may, however, him what causes coUagen to accumulate about the show their own peculiar vascular* degenera- arterioles and whether it may be found in persons . phammena. Its anthracosis.isiderosis, not exposed to dust Ifiosto, talcosis, antiasbestosisj the peri- .Dt'Secerns; Collagen dcpositiesi can occur b uUr lesion is an fmegral anti ifldistin- the lungs apart from dust exposures. There is a weil-lcDowc and growing concept of a group of dls- ^uidiabJe'Componrat of the pathognomonic . eases knows as the coliagesoses. They are char- pirfc^mary'dust lesion, ; * i'Afteriud Jp.cdkccn changes sex only b the bogs parties or fibers* aisd even <butjabob qtber organs, for instance, to the heart, ssbcstoi sxd tremolite bodies may, in most id aoft ttosaes, around joints, and to stances,.be demonstrated within or in rela- ` orgatus;s^ as Ac kidneys. One characteristic type vascular lesions. ^ * ; is the'generalized pulmooary ceHagcnmis of the Hanfroafi-Rieh syndrome mentioned by Dr. Van In the presence of superimposed Infection, Ordstraod. Others include scleroderma, to which particularly tuberculosis, the vascular damage there are collagen deposits to lungs and the skin, may be disproportionately great. This effect periarteritis emA**, and lupus erytbematosis. In is enhanced if there has been associated quartz inhalation. Asbeseosis does not follow these rules directly. coal miners there is *1> sometime* an arthritis as sociated with widntar deposit* to the lungs. la dermatosayositis, collagen is deposited to muscles, iodudtog the diaphragm and intercostal muscles, but It is suggested that these vascular changes no reports concerning lung deposits have beet sub $ayjjx a factor in the genesis of cor pul- mitted as yet In those conditions we do not know OKni^e, though it is not at present established ' what the cause of dial collagen formation h. There that.they may bring about'this resultIn the is more simulation tins facts to the medical Jitera- ^bsence Of.associated physiological disturb ; tore. In the caseof silicosis we do have evidence that ; the silica attracts to the sites of Its deposition to ances leading to anoxia, .; *.'*'., i the tissues the macrophage* and the fiferocytes 5. >'* i* , i r which are normal cellular components of connective ! * ^REFERENCES;*- ^ . : *' t tissue. Collagen Is formed, as far as we know, by )..l, Euler, U. S-.vcsi, and IJIjesuaigL^Q. :*Obse?- f. these fibrocytes, and ccmpk* enryme system* may .tions on pulmonary Arterial Blood FresssrjL in involved. At least we know that to siltodsis the * <jrt.Acta physiol. sandinav. 12j301, 1W4. ' jifiitfocyle have prior existence to the tissue where f%je collagen forms. We also koow that cottages for- 1 it Fishman, A. P.; ^icOement, ; Htowcl- i mation U very largely linked with metabolism of the stem. A, and Couraand, A,: Effect.of 'Acute l< s&prurenal cortex, Hat it why Dr, Van Ordstrand Sa on jh< Circulation and Respiration,to Pa-, { mentioned the excellent response that he obtained with Chronic Pulmonary Disease.1 Studied ! with cortisone and corticotropin, i the "Steady Slate," J, Gin. Invest, SI:770, ; * Msl Rash : To what type of beryllium was the 1551'* rA.- ; exposure to the cases illustrated? Was it a ber- i. 3,;Ccjarirand. A.; Some. Aspects?of the Pol* l gUium,copper-alloy? r$crharyCh?b!atiori.in NormalJMarvdmd in Chruhlc ^ 'Ite'ScHatsas: In the cases of vascular disease to Qafdjopulfeonar; diseases, Citxulatiop 2:64!/l?50. fryvbich *X -referred, ^e industrial exposure was to i- flhSIcMilhael, J.: Dynamif* of jlcarl'Failure. gh^dlimu.oride.dost and oof to beryllium alloy. SV 2rS25,*i9SZ ^ riDx.3. P. Swa*m: Dr. Sch^ers. have you cor- |UeboW, A. ^Bronchopufmonarv Venous t reLrti the blood vessel.changes,with the age of the GettaseraJ Circulation with Special Reference' to /peraon? ltmphy$eroa, Am. /.`Path. 28;25J, 19Sl I * .< . i7 SCfiBPBRS IDfc Sc'Bsms: My data were all dertPpf from persons who wererntdet SO peers of age at the time of death. ) deliberate*/ excluded oWer pexsews from toy study, as we know that certain degenerative changes take place Jo the Mood vessels of oWec persons. A Aid/ of the incidence of these collagen changes at diEerest ages, compared with their reia tfvt prevalence in relation to dust/ 'exposure, is u> progress and will be reported later. Da. S. RISK*?*; Assuming that mineral desis may aS* pidisoaary vascular structures, does that mas that symptoms toay occur without significant or typical rwmgepogram changes? Dt Scaawas t Wbco there are bo space-oceupyktg lesion? to the hmg and if there is oo radiopaque substance in dse perivascular tissues, there will be so shadow an ti* radiogram. Before the x-ray can word on the roentgenograph Sim,* it has to pass through alaxwt a foot ofcheat wall and long tosses. Any au^Mance which will cast a separate shadow eut therefoe be more dense or occupy a certain asvMaK of space m order to be recorded These changes wfaj& etur in blood vessels are fox' the above reasons irtgatattly not demonstrable io the type o( radiograms which arc useful for routine purposes. On the other hand, H those ete radio grams are aqwned form a &fte?cm point of view, i. &, if one searches spedficaUy for evidence of blood vessel damage, it is very irequaitiy possible to recognise cfatges previously overlooked oo merely scanning the same x-rays tor nodules. These lesions manifest themselves through the absence of lung markings (reprcsoiting blood vessels) w*uA were previously demonstrable- Such blood vessel damage may of eourse very easily be desDonHYraSleby means of arteriography or even by tomography which <$plays the vascular atekttectuse of the lungs Quite well. Moreover, one would have the associated radi ographic, ciinkai, awl efectreeardiegTOphic cwdence of cor pulmonale to provide further duet. It wouJd he entirely njasu&*l ta erasers that, because the person in Question has breathed dost, a rignifioaot amount of damage to the blood vessels of his 1ng> must ifto,facto be preamt, even-though it caonot be donona&ated by any known clinical mean*. Tbe con dition mus! he provable in order to be diagnesahfe. Fig. I.--Ischemia of alveolar walls. A, tA&teraooD c? capillary plexus to alveolar waff through macrophage infiltration (Quart* a*d taktotelite exposure). B, destruction of apinary plexus through eoJlagm deposition within alveola? wall ftrcsaoUte talc miner). Fig. 2.--Reduced alveolar wall capillary circulation. A, imtwmtwnt of captikry bed through iyzQpho^tsc sura! tofUtratioa and gMAt-ocll ianftitkr* (beryllium woiVer), B, suveolar asufsi eapi]lanes endrried by irregular eoUagen deposits (asbestos worker). Fig, 1^"-Alveolar wall damage without loss of capillaries, A, preservetioc of alvce&ar wall apulAna despite copious deposition of collagen aloeg central plane around asbestos fibers (asbestos worker). B, oudul&ytsed ajstt&ry pauses causing thickening of the alveolar wall (troB welder). Fi* 4.~-Daaage to small Wood nSs. A, j*oSkrtti c& the rtseuUr rntima with partial dcduswo of the lumen (talc worker). B, ceiJuUr ta&ltration around fibers peoetraonTthe ffioscuJaris (as&estos worker). * Fif. of permactfkt tympSato, A, plasma celt and macrophage accumulation aroano a venule (granite worker), , lymphocytic tUar around arteriole occupying adventitial lymphatic plexuses (uranium worker). COMPARATIVE VASCULAR PATHOLOGY $sw#vi -* --- i&&!i % .y^z m. v> 3&AI Tig. 6.-~Pcriv*sa&r deposits tad faction. A, 4U**c tad mm deposSted around ft Wood vessel with abundant collagen reaction (magnetite muter). S, cellular accumulation about a Wood sl without collages fortnatkm or viscnlar s&cswsi cats supported by retkuiar oetwcrfc (gypsum worker). Fig. 7.--Cumulative perivascular deposits. A, Abundant deposition <rf troo around small artery, with twee eolUge* reaction and partial occJusmw of the fumes (iron miner). B, massive carbon deposit around artery, with partial obliteration of lumen and enlargement of one of die nu nsava <jl ameer). \'Z>7i m3 m 01 7iX*n&> 71 Fig. 8.--Vascular deposition of fibrous dusts. A, ehrysotile bodies within the adventitia of small artery (asbestos worker). B, tresolite bedies within fftdcoa of medium-sized Wood *l (talc miner). F%- 9,--Ifural damage in small blood vessels. A, iadmal proliferation and distortion, with fatty infiltration of muscadaris (asbestos worker). B, deposits of collagen intervening between muscle layers of artery (quarts exposore). Fig. 10.--Obliteration of Mood vessels. A, vessel, trapped withm area of vascular gramilation reaction, -undergoing endarteritis cbtiterans (asbestos worker). B, almost completely obliterated too, displayed within an area of diffuse fibrosis by means of Weigert's stain (quartz-rock miner). Fig. 11/--Relationship between blood roads and nodules. A, Mood vessels trapped within collagen sheath; eristobaiite reaction (fosidry worker). B, Mood vessel surviving within center of siSeotk nodule (magnetite miner). Fig. 1Z--"NetTieo? arttry* simulation in developing silicotic nodule. A, silicotic nodule with prominent Mood vessel in cone of 6broceihikr reaction (flux-cafdned dkf*nitc worker). B. elastic Nekton of occloded Mood vessel, denoastrated by Wogert's stain, within cortical zone of siliortk nodule (qwrts-rodc miner). Fig. 13^--Effect of proxiaaty of nodule* on vessels. A. abortive nodule fuses with cnOagesou* busidles of adventitia of vein (asbestos worker). B, silicotic nodule, abutting on Mood vessel, thickens praxia&l walls hot does cot disrupt elastics catena (quarts and eristohatitc exposure). COMPARATIVE VASCULAR PATHOLOGY Tig. R--Influence of silicotic sodales on adjacent Mood wwli A, Irregular thickening of Mood vessel wails where they lie in juxtaposition to a mass of silicotic nodules (granite worker). S, Effuse thickening of a blood vessel wall opposite a hilar node (quarta-roek murer). Fig. 15.--Pulmonary atheroma in siikosis, A, atheromatous plaque overlying hypertrophic muscutam; cor pulmonale <quartz*rock miner). B. atheroma opposite an adherent silicotic ttodule; no cor pulmonale (qoartx-rock miner). 3L VJue ofJun# EiopSy in the 2$iagno6i4 oj^ Occupationalf-^udmonanj 2)cJea^ed . S. VAH 0M%TTU*1>, M.P. DOWALD t. ifFUX, M.D. WWtENCE i. McCGttMACX, M.0. *d JOHN 8. HAZASfi, WO, CfcvcfMd cerfure usually will prove or disprove ait occupational relationship when multiple methods of study are employed. In our hands, needk-aspvration biopay and scalene node biopsy have not been of significant aid in this particular group of cases. A biopsy of the scalene area can only reveal the disease Qur forebear* well asour ccofrtses have that wilt refiect itself in the scalene lymph taught us what the dimes! and foentgeao- codes. A significant number of diffuse pul graphic findings should be in occupational monary diseases do not show an affinity for diseases of the lungs. This acquisition of the scalene or any other lymph node group. knowledge has been particularly facilitated by We believe that a surgical procedure tike the past McIntyre Research Foundation Con scalene node biopsy that offers less titan a ferences and the Saranac Symposia. 50% yield in diagnosis does not approach the Wc arc, however, also learning that cer ideal m efficiency. tain nonoccupatiooal diffuse pulmonary le sions will mimic those of industrial cause, and lr Is common for the person having pul monary disease to attribute the condition to We have employed a technique of surgical Jung biopsy for a period of five years at the Cleveland Clinic which has permitted study of the lung disease by histopathologic, chem an environmental cause. Furthermore, we do not believe that one should be too critical of the physician who, through lack of training and experience in pneumoconioses, may also ical, and bacferiologic analyses. Although the method is by no moans an innocuous pro cedure it is considerably less radical than the conventional exploratory thotactoiny and first think of the possibility that the lesion is <ii occupational origin. This impression is especially likely in those cases where all diagnostic studies by routine methods have failed to establish an accurate diagnosis. We have found that a surgkaj Jung biopsy ts indicated and usually can establish the diagnosis ? these borderline cases. This pro- may be employed in seriously ill patients who are handicapped by a very low pulmonary reserve. k&tboo The patient is given an appropriate preoperative sedative; a barbiturate routinely is employed. The phamyx and pyriform sinuseV are treated by typical cocaine (4%) by the From Tte Cleveland Clinic Foundation and The Frank . Burst; Educational institute. Dejaartmejit of Pulmonary Diseases (Dr, Van same technique as is used for broncboscopic examination. An endotracheal tube is in serted between the cords, and the positive- OrdsUand) , D*paw*rrt of Thoracic Surgery (Or. Effler); Department of Pathology (tjrv. McCormacV and Hazard), pressure system is applied; oxygen and nitrous oxide (50-50 combination) routinely are employed. Supplementary anesthesia i? 35 VALUE OF LUNC BtOPSY btaiaed by intravenous administration i men also is chemically analyzed. The third thiopental (Pentothal) sodium in very small method of analysis may require a fairly gen doses and a procaine (1%) chest-wail block erous biopsy specimen of diseased lung; over the operative site. Emphasis is placed ideally, a specimen weighing more than 5 gm. os employment of the lightest possible level should be taken and kept in a chemically of anesthesia. dean glass container.* The site of incision is plotted according to the distribution ot disease as it appears on RESULTS the roentgenogram. Usually an anterior ap During the fast five years; lung biopsy has proach is employed with the patient in the been performed in 66 patients at the Cleve supine position. After the skin has been pre land CUnk.f pared, the area is blocked with procaine In 26 of these patients (40%), a question (1%) injected mtcreostally and in line with of occupational disease arose on the basis of the proposed incision. The commonest ap history, roentgenologic findings, or a com proach is through the anterior chest wall on bination of the two. In 1 i patients, the lung either side via the fourth or fifth interspace. biopsy finally proved a diagnosis of an occu It 1% not necessary to remove cither rib or pational disease, as shown to the following cartilage. A small rib spreader is employed Tabulation: for limited retraction, and the pleura! space is inspected. The lung may he retracted into KM f*K"- the wound, assisted by positive-pressure anesthesia, and a representative ares of the dkscaae is selected. The biopsy specimen is A*txTa.......... .........................................i SktoNNla,.................................................. 1 SUMoctt,............................................ ....................................... $ obtained after placing a row of hemostatic sutures around the selected site. Under sterjfe conditions the resected spedmen may be divided into two parts and placed in glass tubes for study in the departments of pathol ogy and bacteriology. An additional speci men is removed m selected cases if chemical analysis is desired. We have found that pre liminary study utilising ffozcn-sectkm tech nique has improved our results. Although the diagnostic accuracy may not be as great as in more conventional methods, the ade quacy of the sample can be assessed immedi ately and often other methods of study indicated. After the sample has been removed, care, is takers to secure air kaks atvd Weed ft should be mentioned that in each of the berylliosis cases the diagnosis was suspected dincalJy before lung biopsy. However, since in each instance the patient represented a single case from his or her company or in dustry, it was our considered opinion that the disgoosn shonVd be established beyond the shadow of medicolegal doubt by both histo logic and chemical means. Beryllium patch tests were positive in each case. Following are repeats of two cases that are representative of those patients having occu pational disease. Case A 4fryear-oJd man was first seen with a problem unrelated to the longs, the roentgen ing points in the lung bed. The lung is reex panded, and the incision is closed in layers, using a simple form of closed catheter drain age. The tissue specimens are studied further in the departments of pathology and bacteri ology, and in the majority of cases the infor mation obtained from these examinations will suffice to establish the diagnosis. However, in those cases in which an occupational dis ease (e. g., berylliosis) is suspected, a speci * Chemical analyses of tlw biopsy specimens In tins series were performed m the Kettering Labo ratory, University of Cincinnati College of Medi cine, fQne mortality oMy resulted from \\m pro cedure. There is considerable doubt as to whether ti* death should be ascribed directly to the surgical intervention, as the patient was actually being kept in hospital for another reason uni died of a coronary thrombosis. We do net belkve this to haee been a complication of surgery. None of the remaining dS case* showed any postoperative morbidity or de ferred complications, 27 t VAN ORVSTRAND ET Al~ Fig, I.---A, roentgenogram of chest of Case 1, showing geBcralUed, fine oodoiation. Prior diagnoses had always been silicosis, although the paten's oa(y occupation of note had been as a welder. <B, stderosis of hmg, Karoeroia macrophages containing a mixture of ajrthracotic pigment and finely divided iron particles. Iron stain; X 130. oarainatioa of the chest showed a generalised, rela-' tivdy fine, not!alar infiltration. The patient brought with him x-ray films and reports that indicated that hu condition had bees diagnosed as silicosis for many years. The only history of silica exposure which could be obtained was of only a few months' duration and not of high concentration. For 25 years, his primary occupation had been welding, and he had never worn any protective device. The examination revealed no evidence of impairment of pulmonary function or of disability. The roent genogram is shown in Figure \A, and the lung biopsy specimen, confirming the clinical impression of siderotls, Is shown by photomicrograph in Figure IS. Case 2.--A 36-year-old man was seen because of a chest x-ray abnormality that had beet noted one year previously on a routine mobile-unit x-ray examination and that had remained unchanged. For approximately one and one-half years he had noted a decrease in effort capacity and the onset of a rela tively nonproductive cough. The history was other wise irrelative other than from the occupational standpoint. The significant feature of the latter was a relatively minor exposure three years previously to beryllium oxide which was being used in ceram ics work with his company. The occupational his tory was otherwise negative. A wording to the p* test and bis employer, 25 other employees had had much more contact with the beryllium oxide than had the patient, but they had experienced no symp toms and had shown no x-ray abnormalities. The findings on examination of the patient were, essen tially negative, with tla exception that the cheat film showed diffuse, fine, granular nodulatkm (Fig, 2A). The lung biopsy revealed a typical histologic picture of chronic berylliosis, as shown in Figure 28, The patch tests to beryllium compounds were all positive. Chemical assay of the hmg biopsy speci men revealed a significant amount of beryllium. The patient was capable of light work and has remained in his employment As he was not significantly dis abled and there was so evidence that It* disease would progress to tliat stage, steroid therapy was believed to be unjustified. The patient's subsequent course has been good, with spontaneous recovery from symptoms. Within the past year, more than two years after initial examination, the arrays show an essential return to normality, as indicated in Figure 2C. In contrast to the above occupational dis ease results, a presumptive diagnosis of occu pational disease was disproved by lung biopsy 28 VALUE OP LVVG BIOPSY Fig. 2--A, roentgencgnun of chest of Case 2, showing fine, generalized, granular ooduUticn. Ex posure id past to beryUiisD oxide is ceramics work. No problem in fellow workers. B, berylliosis of lung. Alveolar membrane diffusely distended by granu lomas composed chiefly of macrophages aad gust cells; a marginal lyrapbecytic infiltration is present Hematoxylin and eo&a; XItiO, C, foilete-up more than two years fetfer, showing spootaacous bearing of the roentgen-ray lesson of betTUiosis. Fmomjrti*# Dlojcosls Patterns. No- 8otfv* pore Wrtory............................... S guggcvtire rotg*7 pfefiw.................... Sas*esUp expoMsr* nslorr tod T*5 An example of each of fltese categories is tUusirated in the following case reports. Case 3<--A 4-year-old man was sees because of symptoms of cough, progressively worsening short ness of breath, decrease as appetite, and a 20 lb. loss in weight during the previous six to eight months. TV* cta3Tonfttic& wastpegWWe with the exception of die rentgenognTB of the chest which showed a bi lateral diffuse leskra (Fig, 3<4), AH standard diag nostic studies failed to provide a satisfactory basis for diagnosis. Both the patient asd the physician who had bees caring for him believed that the pa tient's condition was a result of his occupation, which for several years had been working with vari ous chemicals. Wt did not believe dial the patient's problem was related, to his occupation. However, be cause a definite *hagnosis had not been established by other means, a lung biopsy was performed. As shown in Figure 3d, the biopsy revealed the con dition to be sarcoidosis. The patient's subsequent course generally has been favorable. Case 4.--A 42-year-old man uas seen with the presenting complaints of a relatively nonproductive cough a*nd progressive sbonness of breath of one year's duration. The latter symptom had incapaci tated him from his work. The occupational history 29 4* J--A. rusAgcnograQi of bct of Caie altovtag &&** io&tr*tKjsu Occupational bls- tery fd bp mru tots* sitfia&Surt ts* biopsy diaprbval 5, faaiiog sarcoidosis of hmg. ifany interflitwl grst.aafofMft composed pre4vBta*atiy of atecyoyhages and. ceils. io sweat *}>e graswiomaj ire Rirrouaded fc? <ks*e collages. Heawrtoaylio jm4<lfi; X SC6 Fig. 4.--A, roentgenogram suggestive oj a {meomoeoaioaiS' Biopsy disproved &, fihMsuig interstitial pneumonitis. AH'eotu* watt* are markedly thickened by an aormcu&tiOT of )ympha. cytes and plasma cells. In addition fibtosst is present /oe&Uy a>4 diffusei?. Compressed alwK contain numerous macrophages. Henrafoxylin and eosio; X 160. 30 VALVE OP WUG BIOPSY *'*/' d*r a Fig. $.--*4, roentgenogram of cheat of $4-year-ld employed for 35 yars in glass industry! show ing diffuse, fir*, nodular lesion. Biopsy revealed `m&ary" Ktecaxtttic cardacnia- , aetondary careteoma of tang. Atypical glandular element* in alveoli and lymphatic spaces. Hematoxylin and eosin; XIXl Fig, 6--Roentgenogram showing asymptomatic diffusa Lesion suggestive of a pneumoconiosis ta a 52-year-Id housewife* Biopsy revealed primary Von# cancer (multifocal bronchiofogenie carcinoma, adenocarcinoma ia edl type), Also calk'd adenoaoAoab or alveolar cell carcinoma. ** S+x&A*! .*f -~A* * * MUl*. --...i..`* was multiple dust exposures, but they were believed to b*. of krtuffrrient amount duriog arty one employ ment to account for tfee roentgen-cay abnormality, as shown in Figure 4A. The lung biopsy revealed the microscopic picture of a nongranulomatous, fibrosing, chronic interstitial pneumonitis of the socalled Kamma**Rkh syndrome, as shown in Figure 4B. The patient died tut months after utitixl ex amination. Cass 5,--A 54-year-old man was seen with the presenting complaints of a progressive cough, short ness ot breath, anorexia, and a 25 lb. loss in weight, of eight months' duration. TV* history was other wise noncontribufory, other (has that the pttitns'a life-long occupation had been with a glass company. Analysis ol lus jobs with the company appeared to indicate that they had not entailed a significant de gree of silica exposure. However, lhe patient aod his family though! that the roentgen,ray picture (Fig, SA) was the result cf Ms employment. Exam ination was otherwise negative. The lung biopsy showed no evidence of silicosis and revealed that the diffuse, fine noduiation in Ids lungs waS metastatic adenocarcinoma (Fig, SB). The primary site was never defernuned. The patient died one year after initial examination, and autopsy was not obtained. It can also be merittoAed with reference to roentgen lesions simulating pneumoconioses that there wtte also five cases in women in which the x-rays were suggestive, although in each case the woman was a housewife who 32 * ?** * VAN OSDSTHAKD ' had a completely negative occupational bit* tory, The following case report U an example of this group. Case 6,--A SS-y^ftoM wwras was se because o/ tbc fa&og o a roudae rootsfe-anil cbe^t x~t*y oS the <Siffu* podii/afkw, as shown is Figure 6, She wsj, expesfetctog ne syiaproms ot *cy kusd. The occupational history was wtgalivt; she was a boose* wife. Soutine txftoafiatioaa failed to iadicate a 4tS~ we diagnosis The fcmg biopsy revealed (be pacient's condition to be primary lung oncer ihe form <rf myiriiocal peripfxtid brc&chJokfgeuc carci noma fadenceartiaoma to D type) or to>c*tied tnihrumary adwoatoszs or atveda? ce>] earcjwoaa. The patient tt& of her disease six mootht after i. t1 ttaoiiredoo, SOA* Surgical luog biopsy is a direct ap; to the diagnosis of diffuse pulmonary c where routinely used studies fail to an a diagnosis. It is a particularly impc procedure in borderline eases where it t< erwist impossible to prove or disprove presence of an occupational disease. Ai Cleveland Clinic, surgical lung biopsy established a diagnosis ol occupational ease in 21 such, borderline cases. Poring same period of time, surgical Sung biopsy i disproved a presumptive diagnosis of occuj rional disease in 35 cases. 32 Occupaiionai C^he&t 2$. gjj m tdeaAed in mer6 A fceria* *f Proffos ht fhe (feie of Seutfe Atoee a W. K. $CH?RS, KD , D^<_ Seranw Uke, KY. JNTROPUCTIOX From the purely scientific point of view, the Influence of engineering and medical intervention on the course of occupational diest diseases among miners is the gold mines of the Union of South Africa is of paramount importance because of the magni tude of the mining venture, the stupendous numbers of men involved, the determined gwenatwetai effort* to prevent disease, and the Jong period over which this project has been in operation. The popular misconception is that these gold mines are at Johannesburg. It is true that there stiff are some great mines at this city, but they have long since been dwarfed by numerous mines strung out along the Witwater&raad Reel in the Transvaal, over an arc of about 280 miles from Heidelberg in the east to Kierksdorp in the southwest. Some of the more fabulously wealthy mines are at the periphery and have been hi opera tion in recent years only. In addition to this central series of mines, a new and promising gold Add has io the past decade been mush rooming in the Orartgd Free State at a dis tance of a little more than ISO miles south of the Witwatersrand It is not known yet how extensive this field will prove to be, but rumor has It that it may eventually eclipse the Wiewatersrand in its gold and uranium yield. It is to be hoped that its diseaseprovoking potential will be brought under control from the start. Not to be forgotten also is the eastern Transvaal {Barberton area) where gold was first discovered and Recorded for publication April 6, 1955. Director, The Saranac Laboraier?. mined in South Africa. Gold is sained on a smaller scale also in other isolated localities, and in the Rhodesias numerous mines have been developed. Another popular misconception, which needs correction, is that gold occurs in the form of nuggets. I doubt whether any but a few miners ever sec nuggets of any great size today. They were common in the earlier years of superficial mining, but today most of the gold is recovered from a banket and occurs is a form which can be readily missed by the Inexperienced. Extraction of the gold involves arduous toil, power crushing and milling operations, and elaborate and expen sive chemical procedures. The composition of the banket, spare from its precious metal content, Is approximately as follows: quartz, sibeates, 10%>-2Q%; pyrites, Not only are the mines numerous and spread over a large area, but they are also mostly extremely deep. Depths in excess of 7000 ft. axe Quite common, and in some mines 20,000 ft. levels are being worked. Plans are afoot to descend even farther, but the sharp geothermal gradient is proving a discourag ing obstacle. Loflg-tcrm governmental studies on the effects of environmental Itaaards on the per sonnel operating these mines have been made for the scheduled mines only; but most of the studies on the Negro laborers are ex tremely inadequate for the reason that these men work at the mines transiently and inter ruptedly and because of the vast numbers employed, the excessive annual turnover, and the insufficiency of medical, technical, and clerical personnel available to cope with the problem. Less than 2% of the Negroes are radiographed annually by the Bureau from the point of view of silicosis. All are, however, subjected to 35 mm. radiography 3? SCHBPERS 'jrx Ration 1entering force. They were at a later stage repatriated, studied periodically and it has been a medical mystery what their at these miner Sates were in respect of silicosis r,_ *tuber. Bureaus *^1 as to culosis. are res The next decade brought with it the AngJo- the mine *bes* studies faave been The result* ^>L*jial, annual, at*S special recorded in reports oi th* ((MMiiners' Phthisis) (Miners' Phthhis) Medical Bure** /fs#errrttitn\ Mimng Enp- Boer war for the possession of the mineral wealth of South Africa. In w*ke and following the first flush of military conquest came a growing awareness that for many the price of gold was death. This problem Board, and fff/* y' independent or special was saowonn ritevcooggrnuizzeeod nnoott oonnllyy iinn SSoouutthh AAffrriiccaa neer as wU ** ///* <5<wnw*rt Commit but also in England, where returning miners judications W? J/^oations, and Medical frequently did not survive Jong enough to eions, Mining''/-wring th* ***** * tht enJy * *H *their, by Britishstands. Officers. In 9^ has bee* achieved fabulous savings, gome, ofcourse went trend of progri*'! y/ <he occupational chest home both sick and broke. Ui the suppre.*^ i^cttiBulated in those re- Not all the labor struggles in those first diseases, the relied on. The 10 years of the century were on account of ports will be the b*U>nca> politics or wages. There was growing resttess- reyiew will w.L//-*** wi1} TOVtr ol)8fra' ^ <* a crescendo clamor for an snooty and statistical ft** * period of about into the cause of unexplained disability *nd lions which wWch my U tofo- Ooveraioem commissions took over 60 years in <<**/// f*ogo\xlw, enlighten- and defined the condition of miners' phthisis tomued as \>/f' '/ft****. as s dual disease involving both silicosis and Uient, stasis, *** ' XBASES Rtcogniiio* Problem^ -With this % /Wtor less familiar complicating tuberculosis. The condition be came certifiable as a compensable disease, a*d virtually every med^icif practitioner <m the Whwaferirand of the pioft^^up^ Ifriod {lhwinS tf* *i&~ ?m* ***** in pronouncing **i*ndi^^d '^r already. The j mwwg of gold was not covery and i**rj /mt of view of chest too disastrous .J /J* mining w-vaana in* ti diseases, as mmfl*5""'' ,.,>////// quoaoy workkiinWg and tutture of ope* f*' ,7/ while power-driiling as suffering, or as having 5Uf- from this condition. Not all who were t*h*i ccecirutinfiecud had tthhtt ddiisseeaassee aatt tthhaatt ttiimmee a**dd 8 few such are yet .anliv,,e* today There' **rc no proper x-ray facilities universally * search for tw ,/yaimg the dust clouds mjfcble, and each physician had notions as tools were not jP Hm had tuberculosis to what should rate as pathognomonic cri- experienced ,, > an infecting agent **. The physicians did not always follow wdc its imfrf#*''. ,/iife, the earlier gold the same standards and there was no reason on any signify * ' {{<|y of indigenous stock *hy they should have done so, as few km-w diggers being ff/'/ rJ/f that time a healthful, with any measure of certainty what it wa? twid South ASiM J\,. ttli about. Kpmlrural comt,f* | J/tiwwr, soon brought The lure of tf'"'1 .<! foig**ra from tv> the 'Wttwfllrl 4 i..J {hem came the Myco- Walks in life, an'l !,. The supei*ficiI de- ^eieruiw (|i! *it?,n5`n s were rai , J M* embark on schemes .`irrs were..........O...l.l.l.l^l *' ^<- ... ... Enli#htertt*t*nl.'~-The preceding phase of confusion and legalized sotdical hApharard- Y>ess was brought to a close with the estab lishment of the Miners' J'bthisis Bureau its 5^54 at tlie suggestion of Brig. A. G. Orens^rin. The purpose of %the *B?urea*u was to * deeper an.! Wf "* *"* !,'< were if"l one stage Chinese sm" the hlm tnbercufosis victims n of the hanl-'a^ CHEST BISEASES IN COLD MINERS {crested parties, thus also eliminating.court actions, and to conduct research on the pre valence, nature, causation, and prevention of these diseases, tinder the able direction of its first Chairman, Dr. W. Watkins-Pitchford, the Bureau rapidly brought cosmos out of the medicolegal chaos. Meanwhile, engineering research had made great strides, chiefly under the stimulus of the Chief Government Mining Engineer, Sir Robert Kotse, best remembered today as the inventor of the konimeter, .Adequate proof had by then been produced to suggest a quantitative relationship between extremes of atmospheric dustiness and the prevalence of miners' phthisis. Heroic efforts were consequently instituted to combat the factors which tended to engender dust. This prob lem was, of course, continually aggravated by the ceaseless growth of the mines, the increasing numbers of personnel involved, and the greater rate at which excavation could be effected and gold extracted by means of improved pneumatic drills and high ex plosives and the dab-oration of ever more powerful and efficient crushers and stamp mills. The Government enforced the applica tion of safety precautions through the various Mining Acts and the Regulations under them. Engineers responsible to the Chief Govern ment Mining Engineer ensured that the recommended hygiene procedures were car ried into effect and the regulations properly observed. T>* Bureau's contribution to progress in this phase of enlightenment comprised pri marily the rapid elimination of cases of tuber culosis, tubcrculorilicosis, and advanced sili cosis ami disability from the ranks of active miners. By virtue of its control over the miner's working permit, which it could either issue or revoke, and because it enjoyed the status ofacompensation tribunal, from whose decisions financial benefits flowed automati cally, the Bureau had absolute power in con trolling who could work in the mines. Besides this, the Bureau commanded the best avail able x-ray facilities and pathology labora tories. targe numbers of infected cases were thus weeded out rapidly from the start. Through its function of screening all recruits, the Bureau could ensure that no new cases of tuberculosis entered the industry, and through its system of semiannual, periodical, physical and radiographic examinations, a careful check could be kept on all working white miners with the object of finding the incipient disease. It is possible that the Bureau, preoccupied as it was with the prevalent more serious grades of these diseases, was at first too strict in its interpretations of x-rays in the incipient or less severe cases. Within 10 years from its creation, the government (a recent new o&e) consequently agreed to the creation of an Appeal Board, and the concept of what constitutes a sdntilla of silicosis was formally defined by tlie Minister of Mines, who ruled that, though scintillas may be ignored, the benefit of medics? doubt shook? invariably be accorded the miner. The legal stages of silicosis had by then already been expanded to embrace not only a primary and a secondary but also an anteprimary stage. This phase of enlightenment was also highlighted by the researches of A. Mavrogordato, F. W. Simsoo, and A. S. Strachan more particularly. Watkins-Pitchford, who had held down the dual posts of Chairman of <!* Bureau and Director of the South African Institute for Medical Research, was suc ceeded on retirement by his able first assis tant, Dr. L. G. Irvine, Sir Spencer Lister, the mw Director of the Institute for Medical Research, had meanwhile contributed valu able help to the industry through the elabora tion of a vaccine to immunise the Negro laborers agsfost the prevalent and frequently fatal Pneumococcus mucosus pneumonia which decimated the ranks of new recruits brought in from distant native territories. By now the South African group of re searchers had attracted so much attention through their publications and the success of their campaign against mining diseases that Johannesburg became a veritable mecca for those who sought guidance in the control of the occupational chest diseases, The Bureau's status as a leading world authority was con- 35 SCHBPEftS milthrough the fact that the 1930 Inter- I Conference on Silicosis waa held Or. L. U. Gardner, o? Saraaat take, * at $ 10 ^is Conference. ' Ljfftis---AU was not, however^ on the fjf front even i the midst of triumph. W. flureao had gained the victor's teurth 'I i poon appeared to be resting on them. Mr.. fenipo of research declined. By com- vrith -what had been happening in i^cvious two decades, miners were sisr- W1 lift; and working longer. The general pro1,1 " rate for silicosis at the time of the fence bad droned to 1379 per 1000 f27,87 per 1000,10 years earlier). The iWlsU MI, 0* aS* *t first certification had risen 7 years, as compared with 39.5 years 0, and the victims had managed to W ijjjt an average of 157 months of work, ** jlljywed with s mere 216 months 10 H*,] * !jV*"f*o*'t*e*--. T-he ave'-*ra*^g*e- dXa*tt, VcVou(nWts 1inM tMhle- n hfl<* a^ ^een rei*ucc<f 10 28* particles 0-I |j|jic centimeter (about 7,000,000 par ' kfpr tub* loot). Predictions were that !W- would soon be eliminated. * Tuber- ^T^jli and tubereutosilicosis were already tas properly under control. Over year period I92G to 1929, the number \\* cases of tuberculosis annually disamong white minera who had no if. llV^P had b**ee'*s* s*VeMduVcVeUd fKroWmt4T4IltUo 3^2 (\li-. eC,.,, *STM \ fates of 322 and 207 per 2QCMXXI, teB^lVfly). The production rates for tuber- *y*1 combined with silicosis had also been il0m 8 of 1^3 per 100,000 in tt'r ^ a mere 12 per 100,000 in 2930. 2n y*V ^ years preceding 192% the new case # ^ been 860 and 852 per 200.0CO, re- This seemed like terrific progress ri'V\\u*u\iv wss' ft seemed as chough the an^\ ^ problem had been found and that. s'vV' ^uteau merely continued along the if V* V\liich had been set for it and the engictX**'*'^^severed in ensuring the good housenr' ^ ^bkh itpcrttdVy had been achieved, to** ^ the problem would soon be in sight. lh*'tv ame tlie official point cf view, and Th'1' vVho protested that men were nevertb^*' wing disabled and yet were dying thrX 's risk of being viewed as meddlers ra* ' * and malcontents. 2t became the duty ot the departmental officials to maintain the status quo while a constant political struggle went on all about them. The Bureau's findings were under constant criticism. Scarcely any oi the miners,and few of their family physi cians came to have confidence in the Bureau, which in many quarters was regarded at "an instrument of capitalism" designed to keep the men working whether they were diseased or not, Not even those who had been de clared silicotic or tuberculotk were all in variably grateful, many protesting that they were certified too bit. Under constant pressure from the public the government eventually in 1946 revised and consolidated the Miners' Phthisis Acts and made this probably the most liberal <4 all comparable legislation in the whole world/ No legislation is without flaws, and there were mors also is the new Silicosis Act, some of which were amended in successive years. 2t was perhaps a mistake, however, to iecorporste the Bureau into the civil service. The intention was, of course, good, bur the results were poor. Because of the stratifica tion of seniority and authority apparently necessary to any civil service, tl Bureau could no longer attract the type of skilled personnel needed for its gigantic and special ized task. As fhe Bureau was, in a sense, also a cul-de-sac within the service, the men who joined it found that they could not readily be promoted to other departments. There was no incentive for youxger personnel to stay, and the turnover of the better men was calami tous, The dissatisfaction of the miner? slowly mounted to organized political opposition. Self-criticism by members of ihe Bureau couW not ward this off, which was most dis couraging to those who perceived the need for research. The Bureau seemed to outsid ers to be in the doldrums. Officially, liowever, there was nothing to worry about, as certification rates for silicosis and tuber culosis were continually diminishing, sug gesting that all was fair, fo&rrio#.--Relief came in 1949 when a new government acceded to the pleas of the miners that if silicosis and tuberculous were !W CHEST DISEASES IS GOLD U2NERS not the cause of disability and death among favorable for the Bureau- Reorganization them some other mysterious disease of occu was recommended and put progressively into pational origin was surely decimating their ranks. A Governor General's Commission, under the chairmanship of Dr. Peter Allan, was appointed to inquire into "the occurrence of certain diseases, other than silicosis and tuberculosis, attributable to the nature of employment in and about mines," Accidents were, of course, excluded, as they fell under the purview of the Department of I-abor. The Commission inquired into environmental factors, such as ventilation, mine dust, mine water, blasting fumes, heat, humidity, bac terial content of mines, and work stresses. It also examined claims concerning the pre valence of heart disease, arthritis and rheu matism, dermatitis and other skin diseases, debility, nephritis, parasites, lung cancer, bronchitis, emphysema, and the psychological consequences of mining work.* While the Commission did not find over whelming prevalence of most of these dis eases, it did conclude that "there is strong presumptive evidence that there is a dis abling respiratory condition occurring among miners, which is not recognisable by the usually accepted means of detecting the earliest specific signs of silicosis and which may become permanent," It recommended legislation to provide for the inclusion of such "pulmonary disability" m the Silicosis Act as an independent new compensable entity, and it recommended that the Bureau should be placed in charge of diagnosis and cerrificationof this condition, adding the pro viso that "the methods of medical examina tion at the Silicosis Medical Bureau would have to be modified/' While the miners welcomed the finding of the Commission in respect to pulmonary dis ability, they repudiated the suggestion that effect by the government.* After the Beyers report had been com pleted, pulmonary disability was incorpo rated into the Silicosis Act <1952) as a separate medicolegal entity, and certification and research concerning its nature and prev alence were entrusted to a special com mittee, whose officers were no longer re quired to be members of the civil service. By 1954 more than 700 new cases of such pulmonary disability had been identified among white miners and about 100 cases among the Negro laborers. One of the effects, however, of the creation of this committee was that its much more thorough methods of investigation revealed that many pulmonary-disability applicants {especially Negroes) suffered instead from silicosis or tuberculosis, which had not pre viously been detected by the Bureau. The Bureau, which was meanwhile undergoing reorganization, succeeded in finding these diseases in ever larger numbers, and between 1952 and 1954 certification of new cases of silicosis increased from a little more than 200 per year to more than 1000 among white miners alone. Tuberculosis and tuberculosis combined with silicosis, which had by 1952 virtually become negligible entities, were found in more than 70 white miners in the year 1953-1954. Not only were these con ditions found in such large numbers of men not previously declared to be affected by occupational diseases, but in those who in previous years had been declared silicotic or tuberculotic the stage of the disease was rapidly upgraded. Thus the rate of monthly reclassification of first-stage rilicotics to the second stage (white miners only) increased at accelerating pace from less than 30 per the Bureau be allowed to administer the month to more than three times this rate. necessary legislation and pressed for an Second stagers became upgraded to the third inquiry. stage from a rate of less than 5 per month Once nwre the government acceded. A in 1952 to more than 60 per month toward Governor General's Commission, under the 1954. During this period tuberculosis was chairmanship of a Judge of tlie Supreme demonstrated as a clinical complication of Court, Mr. I). O. K, Beyers, undertook this silicosis in more than 40 cases within a single delicate task in 1951. The result was un year. This was not unexpected, as large 37 SCHEPEBS numbers of siKcotica *ere previously known up unproductive^ toward this end. These to have tuberculosis at death, but by 1952 figures, moreover, reflect the state of affairs the condition had become a rarity as a diag for only scheduled gold stioes whose approxi nosis during life. S;+r' mate statistics are available. The impact on The figures /or Negro laborers underwent similar drastic revision. During 1953-1954 more than 1700 new cases oi silicosis were other mines is by no means ksowtt yet. ft must be realized also that the rapid certification of such large numbers of men demonstrated, more than 1100 new cases of may have serious consequences not only on tuberculosis were discovered in working the earning capacities of the victims but also Negroes, and tuberculosis and silicosis were on the working efficiency of the industry detected to combination in an additional more they service. The Silicosis Act does not, than flOQ cases. This meant that the annual however, prohibit white miners from continu production rates of these diseases were ing their employment in mines except almost trebled. when certified to be suffering from silicosis These stupendous results confirmed the in the third stage, from pulmonary dis suspicion of the miners that all had not ability in the second stage, or from tuber previously been well. culosis. AIJ Negro laborers are, however, A last chapter in the phase of reaction, and which, it is to be hoped, may presage a phase of reconstruction, has been the ap pointment of a further Governor General's Commission of Enquiry under the chairman ship of Dr. S. Qosthuiien, Professor of Radiology at the University of Pretoria. The purpose of this Commission is to recommend a more efficient type of organization of the Medical Bureau, to revise the legal defini tions of silicosis, pulmonary disability, and tuberculosis, and to inquire concerning the need lor intensified research concerning the causation, nature, and prevention of these diseases. l\ is particularly hoped that the Commission's report oh the latter issue will be favorable, for only through research and more research can there be any hope of finding answers to the extant problems con excluded on first certification. Many of the white miners continue in their jobs for the simple reason tiiat they cannot readily obtain alternative surface employment. Many who do depart, with every firm intention never to return, nevertheless tend to drift beck to the mines after variable periods. This medically deplorable state of affairs is due to the fact that the Silicosis Act has never truly attempted to "compensate" the affected men for wage loss or diminished working capacity but instead it pays a system of "'benefits'' which take no true cognizance of the financial loss incurred. The prophy lactic purpose of the Silicosis Act is thereby often frustrated. On the other hand, the system has many advantages for certain persons. STATISTICAL TRENDS cerning the occupational chest diseases. To facilitate recapitulation of the events South Africa certainly has a great deal at of the past 40 years, certain features of these stake. Apart from the personal wage loss, diseases have been graphically portrayed in the discomfort and suffering, and the pre Figures 1 to ?. mature death caused the victims, these dis Occupational Chest Diseases. -- White eases are a tremendous economic burden to the mines. Thus the outstanding liability for die mines in respect of compensation for these diseases has exceeded $15G,OCO,CGO, Miners: The spectacular initial decline in the annual rate of production of silicosis, tuberculosis, and silicosis combined with tuberculosis among white miners is well and currently the mines are paying, in addi shown in Figure 2. 2n respect to both tuber tion, more than $10,000,000 per year in direct culosis and tuberculosis combined with sili costs. To these figures must be added the cosis, it should be pointed out, however, that vast sums expended annually on engineering the rates reflected m this chan do net repre hygiene measures and the capital which is lied sent the total incidence of tuberculosis on the 38 CHBST DISEASES IS COLD UWERS fisuse f `mines. The only cases included here are those which were discovered for the first time in miners who previously did not have silicosis. A tuberculous complication in the latter group has consistently been much higher, and in 194$ it was still Bureau ex perience to find tuberculosis at death in the lungs of 21% of first-stage silicotks, while this rate more than doubled in second- and third-stage silicotks, being quite commonly a factor in the cause of death in the latter cases. Having attained a comfortable all-time low of about 200 cases toward 1950, it is rather disconcerting to find that by 1954 the annual raw of certification had exceeded by three times the highest rate ever recorded at the time when pulmonary disease was previously present at its worst. Of the 789 cases cer tified in 1917, for instance, among 15,000 miners. 257 were in a stage equivalent to the second stage, and 382 were in the tlurd stage. In the year 1953-1954, more tljan 770 second-stage silicotics and more than 400 third-stage silicotics were discovered, though the total body of men from whom these numbers derive now exceeds 30,000, Against 150 new cases of silicosis found in 1917, more than 1050 first-stage silicotics were discovered during the year 1953-1954. To these totals must be added the more than 490 men certified ns suffering front pul monary disability in the first stage (equiva lent to silicosis in the second stage) and the 39 SCrtEPBRS more than 200 cases found to be suffering from pulmonary disability in, |te second stage {equivalent to silicosis in the third stage). The question may be asked whether the Bureau was perhaps applying new standards of diagnosis or compelled by changes in the law to certify these diseases at such an &Unr*ing rate. In the case of pulmonary disability the latter stricture naturally applies, as the hw came into effect in 1952 only, but the criteria for neither silicosis aor tuberculosis had been altered since 1946; prior to this the wording in the legal definitions was slightly different, but there had been no intentional material relaxation In legal standards since 1919, except in respect of second-stage sili cosis certification, which was facilitated in osttain instances since 1946. The answer, therefore, is to be found in the fact that the Bureau itself had com menced to apply new diagnostic criteria ia interpreting the existing definitions. This reduces one to the conclusion that ether the Bureau has recently become too lenient, now perhaps including disease at "the stage of imagination/' or else it previously had been "too strict," failing to acknowledge the existence of established disease until un reasonably rigid criteria had been complied whfc. On the latter assumption, a statistical interpretation would possibly be that cases now certified for the first time in such large numbers represent persons whose disease had been recognized only some time after the earliest detectable sign or the relevant degree of disability had first become mani fest, The trends shown on these curves, therefore, more truly represent animal certifi cation rates rather than annual production rates. At some future period when it has become known whether these trends are maintained or abruptly deflected and after belated certifications have been appropriately antedated, it should become possible to de ride whether the curve of progress should e. 04 I0' 04 04 04 0J 04 I OCCUfATttMAt. CKC8T DISEASES ttftSTOMAMO 0X0 tBMtl WUTK AAfttCA iwwu. moocenw* *u* *EM0 L40OUHEM &*; * ............... * 9 ... trt.MO*' ........ T9TAC 1C* CAfCS wKeO*VTtM*U ft utfin ipso 0* rout * cues of fttcests ^oiscovEcte n f o*r tea* <XC6 ITOO / 5 roiAt mw uses i or TueeAcviosie S .^~0acwffC0 n -, . eextcceyecdas* hoo TOTAL * cases or 'V Tvec*pcwt0-atoss one ret* CKtcn i$e u a a t**e i ** i *j t m * 'too n u u h AHHtUl - ASSESSUSMtS FtSURE S 40 CHEST DISEASES IN GOLD iONERS & redrawn at a generally decelerated rate, as si$gested in Figure 1. Clinical and autopsy experience tends to favor the latter prospect, for the disease at present diagnosed is not as florid a malady as it was in the earlier decades of the century, if only for the reason that tuberculosis now plays a less important role in the incipient stages. The recrudescence of tuberculosis and tubereulosilicosis, shown in Figure l, likewise does sot mean a sudden spread of the infectious element but s prompter diagnosis. In other words, though these cases are now recorded as occurring ia greater numbers than they were encountered during the past 30 years, the disease has not necessarily become more prevalent, and perhaps all it means is that the tuberculosis will no longer be reported for the first time after death. Occupational Chut Diseases. *-- Negro Laborers: lo the case of the Negro laborers (Fig. 2), the production rates of all the pul monary occupational diseases (silicosis com* boned with tuberculosis at the outset ex cluded) haw shown a slow buf steady increase during the past 20 years. The termi nal upsurges shown on the graphs may have explanations comparable to those given for white miners in the preceding paragraphs and reflect altered Bureau diagnostic stand ards rather than epidemic fulmmation of these diseases. The position is, however, materially more serious than among the white men for the reason that Utese annual production rates are virtually based on new groups of employees, the annual turnover of laborers being in excess of 80%. The total labor force exposed to mine dust had in creased by about 20% during these years, being now about 300,000 (scheduled gold mines only), A discovery of more than 3750 cases of occupational chest disease among 300,000 men means an incidence but a fourth as high as among the whites. To this must, however, be added the fact that not all labor ers were examined by x-ray and less than 2% were screened by the Bureau itself, No accurate statistics are available concerning the average dust exposures of these men. but it is probable that the white miners spend three times as many years in tlte mines as do the Negro laborers before silicosis may be demonstrated. Tuberculous, m particular, tends to be a young man's disease among the Negroes. However, during this shorter pe riod the Negroes are probably more directly in contact with dust, as they are truly the miners (drilling holes, shoveling rock), whereas the white men assume the role of supervisors. The steady increase in the total incidence of these diseases among the Negroes may possibly correlate with a tendency toward longer average periods of service performed by each Negro, The increasing prevalence of tuberculosis among the Negro laborers is a discouraging observation. It may be noted that tuber culosis has constantly been more prevalent than silicosis. The Chamber of Mines has taken pains to ensure that these men Itave adequate living quarters and well-balanced diets. Often, however, when first de tected, the disease is Us advanced. Many of the cases are of the fulminating primary type, with a rapid course. But often advanced chronic disease may be discovered too late, and such cases are a source of infection to others, Not until all Negroes arc periodically radiographed will this problem be dis posed of. The tuberculosis situation assumes even more disastrous proportions when It is realized that facilities for the reception and treatment of these men are conspicuous by thdf paudty. Most of the tuberculotics are repatriated, with consequent risk of infecting others at their tribal villages. Others merci fully die within a short time. Yet when modem therapy is instituted, many of these cases respond excellently. It is a travesty of medical idealism that all this should still be happening at a time when the campaign against tuberculosis has made such progress in the United States that even Trudeau Sanatorium had to be closed for bek of patients. The new cases found among the gold miners of South Africa in any twomonth period wouk) fill this vacant Sana torium, At SCHBFBXS *o M M it U 'M 11 n I ** $* t" g rt fc 14 u to 5. SfUCOSlS m SOUTH WTHniMMl #U> MtNEf IIII(I<1/ N ji ii h* }}: VI if/ I *1 :/ iI \ a .11I1It .v 4# \ /^ \ vtotKtcrtoti or * cues or nocosu m MtitkttM to MUTKW or SVtT (ItMims mi mb* ga * MH f|| < cvkC 9S wm. M Ml l*U ** MU rat Ktvtf ms ms. m>. mc pj ma. sis t* out m * *** tu *"* f II / 4/ / t* #/ // < /" a i 9 18 _j 14 * a** ! *s 1 8 * i 4E s 2 j via e*flsr*osdM OS* rt*** or pvs r nreiwe A. flWAt S ts: e t 4 B 8 It n o it }> rt4*s or ftusf txihOiu*r Btfttt of Duration of Service.'--Progress in the campaign against silicosis is shown also in respect to its changing prevalence in tel&twm to duration of dust exposure (Fig3). The decennial cohorts for 1928, 2936, and 3948 illustrate well how miners have been enabled by improved mining hygiene to work longer periods before silicosis mani fests iuc2f as a nodular radiographic disease (Fig. 3 (A|). The tendency in recent years Has been not only to double this period, to judge by the modal peaks o! the histograms, but also for greater dispersion in the occur rence of the radiographic stage in relation to the duration of service in a dusty environ ment, The men have also been enabled to survive almost a decade longer before certi fication. THU, is real progress. However, it must be recalled that the total number of men working at each dustexposure phase diminishes f&pid'y as the years go by. When the decennial cohorts of silicosis cases for the years 1928. J93& and 42 3948 arc converted to per cent annual pro duction rates (Fig. 3 {&)), the difference between 1938 and 1948 is not quite so marked as would appear to be the case when the occurrence of new cases is compared by means of histograms, It is slwwn that the production of silicosis is a function of dura tion of exposure, being relatively more preva lent among those miners with the longest mining service, even in the case of the 3928 cohort. Progression of Silicosis,--Retardation of the rate oi progression of first-stage silicosis to higher stages would be another feature showing progress in South Africa as a result of better stuning hygiene or medical super vision. Figure 4 shows this factor to be dis couraging in respect of the cohorts for the years 1922, 1932, and 1941, It revealed that when silicosis advances beyond the first stage it does so relatively rapidly, and within 10 years after first discovery the majority of cases have already advanced- In this respect CHEST DISEASES IN COLD MINERS fucosi* m SOUTH URICA ' (T*rmuM> mtmt *U cr 4NMML neMeMNM Of M.WOTFS w*Te Men FiOUM 4 the d*<*ft* had not materially changed its character over the past three decades. Refer* en has already been made to the fact that during the year 1953-1954 the Bureau found it necessary to reclassify more than 760 first stagers into the next two advanced categories d the disease. In addition, almost 400 second-stage silicotics were reclassified as third stagers, while an additional approxi mately 70 previously certified miners were found to have tuberculosis complicating the silicosis. This gives a total reclassification of silicotics to higher stages in excess of 1240. During the year 1947-1948, by com parison, the Bureau reclassified but a total of 75 silicotics, and a decade earlier yearly totals of 2S0 or more reclassifications were considered to be high rates of progression.' Once more this exaggerated rate of ad vance must be viewed as a belated correction of previously retarded certification of disease which had advanced but which had not been admitted by the Bureau to have done so. Such cases should for statistical purposes be carried bade to earlier historic periods, as they were derived mainly from the ranks of the surviving annual cohorts of new cases certified since about 1938. When this has been done, the differences in rates of progres sion of the diseases in recent years as com pared with progression among the case cohorts from earlier decades will probably be largely eliminated. In other words, though silicosis occurs less frequently among miners today and takes a greater period of exposure before it becomes radiologicaily demonstra ble, it tends to progress to & stage of dis ability at virtually the same inexorable rate as characterised its behavior in earlier years. This conclusion may be modified by the consideration that the miners today are older when they eventually become disabled than was the case three or four decades ago, when silicosis first made its vicious character nanifest. Perhaps it takes less added pulmonary damage to disable an elderly miner than is required to cripple a young man. Death Rales.--Silicosis: Progress in re spect of the control over silicosis is further manifested through the diminishing propor tion of cases that die from silicosis and the longer survival of the silicotics. Thus of the 1917 and 1921 cohorts of new silicotics, less than 23% survived after elapse of 30 years, the majority having died within the first 10 years, whereas of the 1941 group only about 30% tud died within 10 years from the date of certification (Fig. 5). The rates at which miners died, respectively, from causes a$scribable to silicosis and from other causes became reversed during the past three decades. Thus of the 1927 cohort of silicosis, more than 60% had died from silicosis within 20 years and less than 10% from 43 stucosts in south Affticx rr*4?c*****A *jj ms KAtx A*t tre SCHEPERS other causes.* By 1937 these ratios had 300,000 dust-exposed Negro laborers. Even become inverted so that fewer than 20% of if these approximately 2000 tuberculosis the 1937 group of new silicotics had died from silicosis within the succeeding IS years of follow-tip, whereas more than 20% of cases are to be related to the whole 300,000, rather than merely the 2% examined, we are still dealing with a new esse rate in excess this group had already succumbed to other causes within the first JO years. This reversal is partly explicable on the basis that the average age at certification of the 19X7 grasp of silicotics was less than 39 years, whereas of 600 per 100,000, which is 10 times the attack rate for tuberculosis among the white population of South Africa and twice the rate* found among fee Negroes in fee worst peri urban slums where malnutrition and over the 1937 group had on an average attained the age of 50.$ years when first diagnosed as silicotic. crowding prevail. The mine laborers are well quartered and fed and are selected, on first recruitment, for their robustidty and radio- Tuberculosis.^The problem of tubercu graphic freedom from disease. The high losis is interesting and merits further com tuberculosis rate must therefore relate to ment Argument has often been advanced in their occupation, and the fact that almost South Africa that its statistically alarming half of the eases were instances of tuber prevalence among working Negro laborers culosis combined with silicosis at the outset *s illusory, because i^ade^ntfe tognijance is give* the show away. taken of the fact that more than 300,000 of these men are annually in the service of the gold mines and that the annual labor turn over of more than 80% may exaggerate the number of cases prevalent among working laborers, many of the infections being brought in from outside. During 1953-1954 the Bureau discovered more than 110G new cases of tuberculosis and more than 880 new cases ot tuberculosis combined with sHitosis among less than 2% of the approximately Among the wfiite miners, tuberculosis i$ not quite the statistical menace it is among the Negto laborers, though, of course, it is always a serious problem for the person who falls a victim to its ravages. It is fortunate, therefore, that the disease has been so rela tively successfully eliminated, Figure 6 shows graphically that since about 1923 tuberculosis has not been materially modified in hs ability to attack the young miner. These men Send to be about 40 years of age, and 44 CHEST DISEASES IH GOLD MINERS Tt!9RCVCOS4S AMO TUBUWUtO - feL*CO# VfWOMMB SOLD UMES acwtk *rwu IA Titties > c**f MODetf Mcumwc tZ W 46 M# HSTT MMItOM 0U*l6 -- t6 Li U | A* 2 $, o-5 SM S*t ....... v"* 1URCWUttC wSS** 'sS*<*-**;"*.'..o...m. #**'** *^0**"^'N*- Hi s *X1 s *s S m *. 5 ->**' i*-*'*1 .- r*---- *c,* :. x:;^-^ ......--...... s~ . i" / ^ - * -*$** i --r *r ie mi n5 5E bs m mr me ms xk tuberculosis m soco where from THE WfTWAT6S$RJ*0, SOUTH AFRICA MATH *n TKCNDS FtSURC T the disease appears after about 12 years of dust exposure. Though it assumes tl patho logical character and clinical course of nonoccupations! tuberculosis, it is almost in variably based on some macroscopscally demonstrable preexisting silicotic damage in men with five or more years of service. For this reason South African law wisely treats all tuberculotic miners with more than 10 years of dusty occupation service as cases of silicosis complicated by tuberculosis, whether or not the silicosis has been demon strated in life. It is almost invariably found in the lungs of such men after death. Many tubercufetics with less tha* JO years' service are reclassified as suffering from silicosis as well as from tuberculosis ht later stages. Tubercufosiltcosis, i, e., silicosis and tuber culosis developing pari passu and manifesting simultaneously as a combined disease, com- 45 > \ SCHEPEKS menced originally as a disease of younger miners and is now most prevalent among the older age group (fiftbi4ec&de). Whereas it originally was the main source of death among short-service miners, it tends at pres may have to adjust their sights once more. It. is difficult to imagitte precisely how this can be done, having regard to the rigid precautions which are already being enforced by government and the fabulous amounts ent to he * more benign, more chronic disease already being spent by the mine owners* to occurring in men who had been exposed to metx the specified requirements. dust almost 20 years (Fig. 6). It is by no means the same highly fatal entity as the tuberculosis wbkH becomes grated onto pre established silicosis, and many miners affected by tubereulosilicosis may be completely symptom-lree lor many years, whereas those in whom tuberculosis supervenes on silicosis almost invariably die within six months to two years in spite of sanatorium care. The modem chemotherapeutic and antibiotic remedies have shown some temporary capacity to arrest such tuberculosis. The death rate among tubercuictics has failed to show any significant abatement dur ing the past four decades and may even be worse today than formerly (Fig. 7). Thus, whereas only 26^ of the 291& cohort of tuberculotic miners were surviving ate? 20 years, less than 22^ of the 1938 cohort were alive at the end of 16 years, the majority having died withm the fast 10 years and at a materially more rapid rate than applied in the case of the 2918 cohort. Mo immediate explanation lor this phenomenon presents itself. Pessimism concerning the increasing prev alence of these diseases among the Negro laborers may be tempered with the thought that in the absence of existing engineering and medical control the situation would have been infinitely worse. It is rather obvious, however, that the occupational diseases among these employees need much more exhaustive study. This is logical bit rather more easily proposed than carried into effect having regard to the rapid personnel turn over, language and cultural barriers, and the difficulty in obtaining technically qualified personnel for such an ambitious project. It does not, however, seem beyond the range of reasonability to insist on regular periodic chest x-rays for all Negro laborers. If it is considered a sirtt qua non for the white miners, who are much teas closely In contact with dust-generating processes, U should be so much more necessary in the case of the Negro laborers. The rapid elimination of cases of tuberculous should be the first ob jective, and it is to be hoped that some effort will be made to hospitalise and treat all conclusion tabercaSotics after the disease has been offi The foregoing review of the occupational chest disease problem in the gold mines of South Africa may be summed up as reveal ing overall favorable progress. Ccsv^&t y>, however, by no means yet in sight. The fact tiiat large numbers of the extremely robust white miners nevertheless develop disabling disease within about 20 years indicates but one thing: There is still too much hartnful dost being breathed by these men. Assuming that the generally "satisfactory" dost levels reported in official statistics are representa cially certified by the Bureau. The persuciwss practice of allowing such patients to go "home,,` where they constitute a source of infection to their families and friends in re mote tribal villages beyopd the control of civilized medical skills, should be stopped. TtfoerculosSs was not brought under control in civilized countries by kisses fofre or with out heartaches and frustrations, and the period of isolation can today be greatly re duced through the application of the modern therapeutic agents. tive of mining conditions at sli times, one is Although elaborate prescriptions are given forced to the conclusion that the `'ideal`'dust level of 200 particles per cubk centimeter (approximated 5,000,000 particles j?er cubic loot) is not yet satisfactory. The engineers concerning financial benefits for affected mine employees, the basic approach of the South African silicosis legislation with re spect to the occupational chest diseases is 46 -* -- . *Chbst diseases jx cou> MIXERS pwfhytoas rather than compensation. It Has been shown how this ides! can be frus trated through administrative inadequacies, and it is to be trusted that precautions will in the future be taken to obviate the recur rence of events referred to. Research only can solve the puzzle of persisting disability, de spite all the precautions that have already been taken. REFERENCES 1. Report upon the Worfc ofthe Miners' Phthisis Medical Bureau tor the Three Years Ending July 31, 1932, U. G. 22, 1933, Government Printer, Pretoria, Union of South Africa. 2. Act to Amend, Consolidate, and Extend the Law Relating to Miners' Phthisis, Act 47 of 1946, Government Printer, Pretoria, Union of South Africa. 3 Report of the Cotnmie&too of Enquiry Regard ing the Occurrence of Certain Diseases, Other than Silicosis and Tuberculosis, Attributable to the Nature of Employment in and about Mines, U. G. 22, 1951, Government Printer, Pretoria, t/rubn of South Africa. 4. Report of the Commissioo of Enquiry Regard ing the Fu&ctkxvB* of the Silicosis Medical Bureau U. G, 1952, Government Printer, Pretoria, Union of South Africa. 5. Act to Amend the Sihtosia Act, 1946. Act 63 of 1952, Government Printer, Pretoria, Union of South Africa 6. Report upon the Work of the Silicosis Medi cal Burov lor the Three Years Ending March 31, 1948, U. G. 64, 1949, Government Printer, Pretoria. Umon of South Africa. 7. Report upon the Work of the Miners' Phthisis Medical Bureau for the Three Years Ending July 31, 1938, U. G. 40, 1939, Government Pricier, Pre toria, U&ioc of South Africa. & Report upon the Work of the Mwer*' Fhtfusis Medical Barcaa for the Twelve Months Ending July 31, 1924, U. G. 46, 1925, Government Printer, Cape Town, Union of South Africa. 47 ^Iccomplhlmenti in the ^dpidetnioio^ic Stud^ ojt ^iiicoih in ilte 'United delated H. N, DOUf. $S. VICTORIA R T*AS>, A.*, W. M, 6AFAKR, Die end $. E. MtCUK, RQ, Woifev^t^, C. C EARLY SILICONS For this group there is Util* need to re port the chaotic situation that existed when the United States Public Health Service, In cooperation with the United States Bureau of Mines, undertook its first investigation of Should an early investigator of silicosis return to the industrial scene, he might justifiably be surprised that, after many decades of study, (his disease has still not been vanquished. Yet these a?e some who, though not removed from the industrial scene, have yielded to the complacency that full control ol silicosis has been achieved. It is therefore timely, as we move farther into a technologic era in which radiation and other modem hazards compete for attention, to review the status of this old industrial plague. Id the United States, many groups, both nongovernmental and governmental, have made noteworthy contributions to (he cluci* data of (he problem of silicosis. A review of at? their efforts would not he practicable at (his time. It is therefore the purpose of this paper to review only the accomplish ments of (lie United States Public Health Service and to inquire into the present status of silicosis in the United States with the use of da?a made available to this agency. silicosis in the tri-state area of Oklalwata, Kansas, and Missouri in 19J4.1 At that time, medical knowledge was far ahead of our techniques for measuring die workers' ex posure. Consequently, in this early investiga tion, very little information was developed about the environment. Even at this early date, however, the iavesiigators realized that the ultimate solution of the problem would depend on the correlation of the medical find ings with dust concentration. This study was oae of the earliest attempts to apply x-ray (o mass diagnostic procedures. It is of historical interest that, of the 220 miners examined, 433, or 60%, were diag ramed as having '`miners' consumption." In 103 of these cases, tubercle bacilli were dem onstrated in sputum samples. In addition, there were 43 miners with a doubtful diag nosis ; 26 were suffering from miscellaneous nonpulmonary diseases, and 39 bad uncom plicated tuberculosis. Ot the 453 tsanm, 120. with an average age of 31 years, showed first- stage silicosis; 142, with an average age of 33, were second stage; and 0$, with an Recorded /or publication April 4, 19SS. average age of 38. wete third stage. Chief, Occupational Health Program, Division of Special Health Services (Mr, Doyle); Program Adviser, Occupational Heakh Program (Mist Tmfeo); Technical Adviser, Occupational Health Program (Dr. Gsfafer), and Chief, Division of Serial Health Servkts, PuWic Health Service, U S. Department of Health, Education, and Wel fare (Dr. Miller). To reemphasize the drastic social eon**, quences of the disease during (his era, let us briefly review several case histories, Mrs. C. lost two husbands, aged 38 and 48; one son, aged 2S, and one son-in-law, aged 34. Mrs, L. lost four brothers, aged 40. 42, 44, and 46. Mrs 1'. lost two brothers aged 30 4* EPIDEMIOLOGIC study of siucosts snH 28; a half-brother, aged 30; a husband, aged 29, and a brother-in-law, aged 28. Those are but a few of the many cases of family hardships caused in this one particular area by silicosis. This is not given as scien tific evidence bearing on the problem but to illustrate the social and economic implica tions of sificosts of that time. Conclusions drawn from this study are also interesting in view of our present knowl edge of silicosis. Some of these were stated as follows: ]. Miners* consumption is an important occupa tional &stase prtvaSem amca^g thehard-rock ethers of the Joplin district, affecting probably 30ff to 359b M them. Z Miners' consumption is essentially a pceunocomosls doe to the inhalation of siliceous rock dost and resulting fa a fibrosis with loss of function. i The disabilities and other factors of miners' coMumpdoa arc due primarily to silicosis, tnieetioo being usually a secondary and often a terminal process. 4, defection, both tuberculous and pyogenic, it common So miners' consumption, the tendency to ward infection recreating as (he disease progresses. The tri-state study formed the basts for a series of Public Health Service investiga tions in the dusty trades during the 20's and 30`s, which included the cement, asbestos, coal, tak, and granite industries. Forty* nately, by 222 dust quantification methods had been improved, and it was thus possible to include in these studies fundamental in vestigations of the environment. The study of the granite industry, undertaken in 1923 by the old Office of Industrial Hygiene and Sanitation of the Public Health Service, was the first epidemiologic study of silicosis in which it was possible to correlate definitely the worker's physical condition with hts en vironment,* This introduction of epidemi ologic methods* which considered both the worker's environment and his physical con dition, probably represents the most signifi cant contribution that the Public Health Service has made to the study of silicosis. The granite industry study served to add materially to our knowledge of the pathology of the disease by constructing s graphic pic ture of wfcaf happened to men working for many years under dust hazards of a known character, Among the significant factors were the following: (0 The long period of service before the liability to tuberculosis became manifest, generally 20 years or more, (2) The sharp correlation between the length of exposer? to the dust and the prevalence of tuber* eulosis, and abo the death me from this disease. (3) The dose correlation between the extent of dust exposure and the health of the miner. (4) The universal occurrence of silicosis among the workers exposed to concentrations above 40,000,000 particles per cab*.fart <pcf) of air. (5> The large proportion of workers who finally succumbed to tuberculosis. (6) The almost tavariabfe fata! farm of the dis ease (silicosis) within a short time after the onset (?) The differs* character of silicosis, as zuantft4 by x-rays, compared Tri* that where the ex posure was to a dust with a much higher content of free silica. This fast conclusion was contested by Gardner in 1939, his thought being that k may have been due to improvement in x-ray techniques.* On the basis of this study, it was possible to form some rough ideas of the limits of dustiness which may be regarded as reason ably safe from a health standpoint. Silicosis was universally present in those groups where the average dust content of the en vironment variedfrom 40,000,000 to 60,000,OOG pc? of air. There was Kttk indication of any serious effect on the men with average exposure of about 20,000,000 pcf. In the group where the average concentration was 6,000,000 pcf, there was no indication of any unfavorable effects on health. Thus, it ap peared from the analysis of the data that a safe Unfit to this particular dust, with a free silica content of approximately 35%, was between 9,000,000 and 20,000,000 pcf of air. Out of die granite study grew an extensive silicosis-control program, instituted by the Industrialllygiene Division of the Vermont Department of Health. Briefly, this program was based on an agreement between the granite manufacturers and the labor unions to initiate dust-control measures, which would be periodically checked by the Ver- DOYLE ET Al~ moot Department of Health, and to provide annual x-ray ocanunatkxt of workers. I* m Interesting to note that, insofar as records show, not a single case of silicosis has devel oped in a granite-shed worker whose initial exposure followed the installation of dust controls.* This is the only known example of a United States industry in which it ap pears that no new cases of silicosis are de veloping. However, there arc a number of factors which must be analysed before we can assume that such success has been or could be attained in other industries. The Public Health Service studies of dust diseases, conducted between 3913 and 1935, made several important contributions to the study of silicosis. These studies served to confirm the findings of many independent investigators and assisted in determining the pathology of the disease. They helped im measurably in the assaying of dust exposures and in defining the role of such factors as particle size, composition of the dust, and duration of exposure and led ultimately to the adoption of 5,000.000 prf of air as a maximum allowable concentration for silica dust. The year 3935 or thereabouts saw recognition and acceptance of the five cardi nal factors m the etiology of silicosis: com position of the dust; the concentration of the dust; size of the dust particle; duration of exposure, and individual susceptibility. Because of the netd to concentrate on other disease entities, 3935 also saw a di minishing emphasis by the Public Health Service on epidemiologic studies of silicosis. This decision was undoubtedly influenced by the assumption that the silicosis problem was largely solved and that prevention was sim ply a matter of applying the necessary en vironmental controls. This feeling apparently was shared by others, for at the Fourth Saranac Symposium Drinker stated, "To be sure, the clinical and biological aspects of silicosis leave many problems unsolved, but the preventive aspects are now in fair order/'1 The middle 30's also marked the introduction of extensive dust-control pro- Ahe, H, B,: Personal communication to ti>e authors. grams by the larger mining and industrial companies. The 20 years that have elapsed since the institution of dust-control measures may be regarded as a period of observation for de termining whether these accepted preventive techniques are in reality adequate. It is therefore timely to appraise the effectiveness of control methods for silicosis. PRESENT STATUS OF THE SJUCOS1S PROBLEM As a prefatory note, it should be recalled that statistics on the incidence of occupational diseases, including silicosis, have always been notoriously poor in the United States. With 4 states with differing requirements or none at all. It ts not feasible to set up a central collecting system. In the states that have some kind of reporting scheme, lack of com pliance, problems of interpretation of case histories, and differences in classification of the disease and in nomenclature are other discouraging factors. Despite the fact that medical reporting to Health and Labor De partments is compulsory ia many states, it is ineffective as a source of incidence statis tics. Numerical information, however, is available on silicosis incidence, but it is un coordinated, scattered, and subject to various interpretations. The main sources are com pensation records, medical and environmen tal investigations in specific industries, and routine examination programs. We have been attempting to overcome the gap by gathering statistical data on the extent and scope of the silicosis problem today. This study, under way since November, 1954, seeks to determine how many silicones there are as well as when they received their major dust exposure--whether it was before or after 1935, which we are arbitrarily setting as the year when industry began on a sub stantia! scale to install dust-control equip ment. At the Fourth Saranac Laboratory Sym posium on Silicosis. Chmmings ventured a guess that not more than 50,000 employed men might be found in the United States at the present time with definite evidence of silicosis,* Exact knowledge of the mambet SG BPIDBUIOLOGIC STUDY OF SILICOSIS ol potentially exposed workers in the United States then, as today, was not available. Among the more reliable estimates was the one based on the preliminary survey (1936*939) ol the industrial hygiene problem in the United States by the Public Health Serv ice; the Dumber of persons potentially ex posed to silica dust was estimated to be 1,500,000.* In terms of today's status ol the silicosis problem, the implication in these earlier esti mates can give rise to deep concern. In view ol the slow clinical course of silicosis, work ers who received their major dust exposure in the 30's or early 40's could be expected to show signs of the disease and disability at the present time. Although tSust-conircA equipment was beginning to be installed in TMia 1*--Ce*Kpe*sciio* Dole on SHicstu " .....-3' ........B state Cofendo C**S Ti JQtr, *& TlM.UW teuuyfrt&ii. isso>io& lEfeott C*S(ndt lMM U6M&M Type Cue* trogwwd Ct*t rrof^Md C*M Proe*M nM tans cioal DJfpotce 99Q b*fR tbc ^Omr, No. SitHtood* ttrfUcotJe 1SSaf14e* l.USwLhr***tBeoafe fptflwosa MSp&ewnooatala the middle 30's, the achievement of universal coverage was many years removed, A big educational job lay ahead. Management and labor had to be taught not only how to pre vent and control dust diseases of the lungs but also that certain dusts in excessive ex posures were dangerous. Asa matter of lact, the job is still incomplete, lor two decades later many plants can be found without dust control. In other words, despite whatever progress may have taken place in cleaning up dusty working conditions, we are likely to inherit for years to come a sizable preva lence of siltcosU. Comfettretten Dose.--A major source ol information on the extent of the current silicosis problem is com;>ensaIso?5 records. Table 1 summarizes the experience in six states within recent, but differing, periods of time. Because of differences m compensation laws in the states, it is not possible to make comparisons and draw valid amclusiont. For this reason, only & description of the data can be presented. In Colorado, in a 30-month period July, 1952, to December, 1954, there were 34 cases of silicosis processed. Of thest, li were com pensated ; IS were dismissed or denied owing to late Irirctj, to absence of rota! or permanent disability, or for other reasons, and 5 were pending decision. Sixteen of the affected workers were reported to have begun their employment in industries with exposure to silica dusts after 2935. Twenty of the men worked, in mints, 10 in foundries, 2 in smelt ers, and 2 in tins firebrick industry. In Utah, the medkai panel of the State Industrial Commission made a diagnosis of silicosis in 24 workers during a three-year period preceding 1954. Four hard-rock min ers were alleged to have received their ex posure after 1935; one worked at his job 6 years, another 14 years, and two others 17 years each. The ocher 20 workers received their exposure before 1937 or both before and after. Eighteen of this group were hard-rock Winers, and two were mill workers. Six of the miners also had tuberculosis. In West Virginia, the Industrial Cootmis sion processed 1523 cases ol silicosis in 1953 and the first 10 months ol 1954. Fifty-eight H-ere fatal West Virginia compensates for partial disability, and, of the total processed, three-fourths received compensation. In Pennsylvania, during the three-year pe riod 1950,1951, and 1952, &total ol 305 cases of sittcosk and 3115 cases o{ amhracosilico sis were compensated. In Illinois, $7 com pensation datms for silicosis were dosed dur ing the three-year period 1951 to 1953. In California, the Industrial Accident Commis sion issued 82 original decisions involving pneumoconiosis during the fiscal years of 1953 and 19S4. Only cases h which there is a dispute come up before the Commission. It is of interest to note in connection with these compensation data that, although we have no recent figures for Montana, in 1947 some 600 persons were receiving benefit pay ments as silicotics. 5! DOYLE ET AL. X-Ray Examination Dais---Another source of informalkrais the x-ray *efcamination dala accumulated by the divisions of in dustrial hygiene in the stale health depart ments of Vermont and North Carolina. out of 2226 workers in the foundry industry and 38 of 328 slate workers showed evidence of silicosis in one atage 01; another- The period of major dust exposure has not been ascertained for these cases. Table 2 shows a comparison of x-ray find ings of workers in the granite sheds of Ver mont in 1937-1938, when dust control equip ment was being installed by the manufactur ers, and again in 2954. X-ray examinations Since 1936, the Division of Industrial Hy giene of the North Carolina Board of Health has been x-raying workers and conducting studies of the working environment in dusty trades applying for or carrying workmen's in 1937-193$ of 80S workers disclosed 365, or 45%. with rilicosis; examieaiions in 1954 showed 20% with silicosis. In 1954, the in cidence rate based on the payroll employment of 1809 granite-shed workers was 16%; in sofar as it can be determined from occupa compensation insurance for silicosis. This responsibility is delegated by law. Legal pro vision is also made for physical examinations of prospective employees and periodic exam inations of those engaged lb industries with harmful dusts, with a stipulation for the re tional histories, all the affected workers rc- Tasle Zr-SWcorie (AH Sieges}, Graniie-Cultmg and Finishing Industry of Vermont Itta ISBMflK wu payroll enpleytBeoc.............. 1,193 iJOd WojS*rt *-r*r*a, ............................... as i#t Woiter* x*nya v]Ut SJafowt* el *ffl MU,tea,.......................................................................................... *S *i* Waasrk<tanuotn pM*rrtoDbums tMbemt ktoasisUHx<Uenarteedri re*?, eo................. ........... ..................... Tetfil wfO cSeoaU...................... IBS SM Worker* x-med fraud vttb *ai <oM. ft............. 41 ccived their initial exposure <0 dust prior to the installation of dust-control equipment. Of the 294 workers with silicosis who are still employed, 42 also have some form of possible infection, such as tuberculosis. In 1937-2938, the corresponding number was 143. A workmen's compensation law was passed recently in Vermont providing com pensation for total disability due to silicosis. Relatively few claims have been filed, how ever, since the granite cutters either are not totally disabled or prefer to remain at their jobs as long as they can. The Vermont Division of Industrial Hy giene also takes routine chest x-rays of work ers in other industries. In 1951-1952, there moval of employees ia the very early stages of the disease. The program is carried out .In conjunction with the Industrial Commis sion, On the average, 2500 to 3503 workers appear for x-rays annually. Most of these workers are engaged in the mining and mill ing of tungsten, mica, and pyrophyllite and the quarrying and cutting of granite and stone. Since 1936, as a result of the state's physi cal examination program, 446 workers were diagnosed as having silicosis. Tabic 3 gives a distribution of cases for major industry groups according to five-year intervals dur ing which positive diagnosis was first made. The five-year grouping ia for convenience rather than to show any increase or decrease in incidence, because the number of new cases uncovered is dependent to a great degrn on the coverage oS industries by the x-ray survey. Unlike the data collected in Vermont, the available information for Nonh Carolina does not lend itself to determining incidence rates. Workers found with silicosis are denied a workeard and either file a claim for compensation or find employment in nondusty industries. Thus, they do not always reappear for periodic examinations. An opportunity was given to review in dividual records of 40 cases diagnosed as were 16 to 419 quarry workers x-rayed who showed evidence of silicosis, The years of exposure were long in all instances. Eleven having silicosis for the. first rime in 1953 or 1954. Occupational histories indicated that 20 of these workers began employment in 52 EPIDEMIOLOGIC STUDY OP SILICOSIS dusty trades after 2935. Five of the recently affected workers were under 40 years of age and had a mean average exposure to dust of 23 years; 5 were between 40 and 49, and 10 were over 50 years of age. MctioiUy Siolist&s. -Further information In the form of unpublished data on deaths from occupational respiratory diseases in the United States has been provided by the Na tional Office of Vital Statistics, These data are shown in Table 4. Over the four-year period 19*9-1952, they reflect an average of more than 1200 deaths per year from silicosis and anthracosilicosis combined, about 600 deaths per year from respiratory tuberculosis was the only cause of death mentioned on 21 of the 64 certificates; sUicotuberculosis was given on 26, and for the remaining I?, other causes were also stated, A rough distribution by occupation re vealed that 18 were miners and another 28 worked in the granite industry, foundries, and other trades generally associated with silica-dust exposure. Another 28 were re ported In occupations not usually associated with silica exposure, such as farmers, jani tors, store clerks, and guards. Ten certifi cates did not state occupation or gave the occupation as "laborer" without further ex planation. The inadequacy of the kind of Table 2.--Number of Coses of Silicosis (All Stores) According to Period When First Diagnosed W by Industry in North Carolina ZWtod 12MU................................................. Tout,.,...................................... TofAJ U&tBxtB4 ss? to S3 ADdSlooe Uxtucoy v K fl U> 813 U6 Fooadrtea u $ e t S3 OUr $ 9 6 9 to Tabus 4/--Deaths from Occupational Respiratory Diseases, J9i9'l?S2r for United Slates (Sititm&i Office of Viol Statutes. Pcfrfic Health Service) Cbmc o! Detb Brmilrttnrr tobowto*# wtUa bcsum of Meoj>*ttoiu>t da- mm of feat.................................................... ......... aoiH& **t *Mir**m*k........................................................................... Ostar p*unoJ*........................-..................................... ............ MQ SB JJtt S3 IB& ? U 8 19S3 B5 JJW B Uk9 ijcr JrJ with mention of occupational disease of lung, and 225 deaths per year from other pneumo conioses, probably chiefly silicosis. Age or occupational analysis of the deaths is not available. An analysis of 64 death certificates naming silicosis or pneumoconiosis as a primary or contributory cause of death in one state (Kentucky) shows that silicosis is present at all ages but tends to increase in impor tance in the older age groups. Five of the workers were between 30 to 39 years of age; eight were between 40 and 49 years. For six of these workers, the cause of death was given as silicosis or pneumoconiosis without mention of other conditions; for five, silicotuberculosis; and for the remain ing two, other disease conditions. Silicosis information contained in death certificates is readily apparent. CUSiENT INVESTIGATIONS AND STUDIES It was not meant to Imply earlier in this paper that since 1935 the Public Health Service has had no interest in silicosis and other dust diseases. With its extensive his tory of research in dusty industries, the Oc cupational Health Program of the Public Health Service has every intention of pur suing appropriate studies whenever it is in dicated that a significant public health prob lem exists, In 1949, evidence pointed to the foundry industry as a significant source of exposure to silica dust. Consequently, the Public Health Service, in cooperation with the Illinois Department of Public Health, undertook a study of silicosis in the various S3 DOYLE ET AL foundries of Illinois.* As might be expected, the most significant findings pertain^! to the respirator)' system. Pulmonary fibrosis of occupational origin was found in 9.2^& of the 193? men examined. The clinical and environmental findings revealed that there is not so prevalent as it once was among silicoeies, and, needless to say, because of our present compensation laws and enlighttn?d employment piacuce*, the disease no longer has extreme and unique social con sequences. Examination of the data also in was reason to believe that the dust conditions io the foundries had improved in tbt past 10 to 20 years. Thus, it is likely that in most instances the pulmonary fibrosis observed was due in great part to the higher dust con centrations which probably had existed !G or 15 years previously, The conditions noted, however, generally left room for improve ment in the control of silica as well as other hazards. dicates that there is a longer period of de velopment of the disease than was true in the early days. You may recall the average age of those suffering from third-stage sili cosis in the tri-state study was 38 years. Al though we have not compiled an average age for present-day silicosis, it would appear that it is somewhat higher. UNRESOLVED QUESTIONS In 1953 and 1954, in cooperation with the health departments of California, Nevada, and Oregon, the Public Health Service con ducted a comprehensive clinical and environ mental study among workers engaged in the mining and processing of diatomaceous earth in five plants, three handling salt-water diatomite and two handling fresh-water,dialOmire. Approximately 900 employees were examined. The prevalence of pneumoconi osis, similar in type to that reported in 1952 by Smart and Anderson," was sufficiently high to confirm the existence of a pulmonary hazard in this industry.f Preliminary indi cations arc that the major danger lies in the crystalline forms produced by calcining of the amorphous natural diatomite. Prior to the study, recognition by the industry of the need for rigid controls led to progressive reduc tion in dust exposure, and so correlation of current environmental and clinical data is misleading. Plans are now in effect for pe riodic follow-up observations to determine the effectiveness of control measures -now being applied. From the foregoing statistics, crude as they may be, it is apparent that silicosis is yet a major occupational disease in the United States. Our limited information, however, indicates that tuberculous infection The continuing occurrence of relatively large numbers of cases of silicosis raises some questions. It Is not the purpose of this paper to attempt to answer these questions, but simply to pose them as areas in need of further study, A number of questions fol low: 1. Do the initial exposures m these cases date back to pre-dust-control days? If so, do these cases represent progression of the disease due to continued exposure to low concentrations of silica dust? Certainly, the age range of many of the cases indicates tbat they may have received their initial exposure before dost controls were generally adopted by the mining and manufacturing industries. 2. How extensive and efficient is dust con trol in relation to recommended standards? Doubtless, there is a large volume of data available in official and private industrial hy giene agencies which would have bearing on this problem. As yet. however, these data have not been analyzed on a mass scale, 3. Do our standards need revision ? There is no ample evidence at this time to indicate that the 5,000.000 particles per cubic foot (pcf) of air are not adequate. However, *s with other industrial hygiene standards, this standard should be under constant scrutiny. 4. Are iterc other factor?? to which we 1 Geoipatonat KuUh Pregsam, Division of Special Heal'h Services. U. S. Public Heal'fc Service: Unpublished data. are not giving proper consideration, such as particle size of the dust? Mention of this problem is frequently found in the literature. 54 ewras: BPIDBHIOLOCIC STUDY OP SILICOSIS The Third International Conference of Ex perts on Pneumoconiosis pointed up the seed for additional research in this field, stating that "the lower sire limits of injurious par ticles had not yet bees determined/'f 5. What is the actual toxicity of silica? The diatomaceous-oarth pneumoconiosis study indicated that noncrystalbue forms of silica, as well as cristobalite and tndymite, produce a pneumoconiosis which is not sili cosis per sc but closely related to it. The predominate opinion of investigators of coal miners' pneumoconiosis is that the small con centrations of crystalline silica to which the worker is exposed have no significance m the etiology of the disease.* There are others, however, who maintain that these small con centrations* may have a significant relation ship to the problem. This point still needs to be resolved. These are questions which are of real in terest to the scientist and must be answered if silicosis is to be completely eliminated as an industrial disease. In the compensation field also there are problems which will need scientific evsfaatron before the compensation and social aspects of the disease are com pletely resolved. These problems are asso ciated primarily with the need to devise prac tical means ofassessing disability. This ques tion becomes more acute as more states com pensate for partial disability. Indeed, there is still great need for the development of a satisfactory x-ray classification. As you know, this problem is being considered by a committee of experts in the United States, and an international classification system has been proposed by the International Confer* ence of Experts on Pncumoconiosis.f CONCLUSION From this review of dust studies of the Public Health Service and the data made available by other sources, it may be con cluded that the problem of silicosis in the United States is still far from being wived. Several obstacles yet remain fo be hurdled. JRriwence 7, p. 130. primarily m the resolution of technical ques tions. The following agendes cooperated io providing information relating to the silicosis problem: *dustrial Hygiene Diriuoc, Vermont Department of Pablk Health; Division erf Industrial Hygiene, North Carolina Board ol Health; State Compensa tion Insurance Ftmd, Industrial Conwnisslon of Colorado; Utah Industrial Commission; Industrial Commission of West Virginia; Bureauof Research and Information, Pennsylvania Department of Labor and Industry; Division of Labor Statistics and Re search, California Department of Industrial Rela tions; Division of Statistics and Research, Illinois Department ef Liber; Kostvcky Stast Department <rf Public Health, and Nation*) Office of Vital Sta tistics, Public Health Service, U. S. Department of Health, Education, and Welfare. REFERENCES 1. Lana*. A. j.: Miners' Consumption: A Study of 433 Cases of the Disease Among Ztoe Mine's in Southwestern Massoori, with a Chapter on Roentgen Ray Findings in Miners' Consumption, iy S.B. Child*, Bulletin $5> United States Treasury Department, Public Health Servlet, 1917. 2. Russell, A. E-, and others: The Health of Workers in Dusty Trades: II. Exposure to Silicious Dust (Granhe Industry), with sections on au topsy material by L. U. Gardner and on silica by A. Knopf, Bulletin 387, United Starts Treasury Department, Public Health Service, 1939. 3. Koechte, By ., editor: Fourth Saranac Labo ratory Symposium on Silkesls Hdd in Connection with the Trudeau Scheol of Toberculotls at Saranac Lake, N. Y., June 19-23, 1939, Wausau, Wis., Employers Mutual Liability Insurance Co, 2939. 4. Bloomfield. J. J-, and others: A Preliminary Survey of the Industrial Hygiene Problem in the United States, Bulletin 259, United States Treasury Department, Pubbe Health Service, 194a 5. Division erf Industrial Hygiene. U. S, Public Health Service, and Division of Industrial Hygime, Illinois Department of PuWk Health: Health of Ferrous Foundry-men in Illinois, Publication 31, Federal Security Agency, Pablk Health Service, 1950. 6. Smart, S. H, and Anderson. W, M,; Pneu moconiosis l>oe to Diatomaceous Earth: Clinical and X-Ray Aspects, Indus*. Med. 21:509-538 (Nov.) 1952 7. Third International Conference ol Experts on Pneumoconiosis (Sydney, Feb.-Wareh, 1950): Record of Proceedings, Geneva, International Labor Office. 19S3, Yd. 1, * 15. 8. HfTvrfeston, A. G.: Coal Workers' Pneumo coniosis, A. M. A. Arch. Indust. Hyg. 4:270-288 (Sept.) 195i, 55 \: \ ( I 1 Ii >i `I 'I*. *Silico6i6 in (Canada N. f. PARKINSON, M-f* TosMto, Ccaoda The statistics on the incidence of silicosis in the Province of Ontario and jo the rest of Canada over the last quarter-century are somewhat lacking. The reasons for this are twofold, and they seem to be equally comma in otter parts of the industrial and mining world. They are as follows: 1. In our mining ipdustfy from, 1926 to 3930, the exposure tune needed to produce silicosis was about 3 5.4years. la the interval 1951-3953, it increased to nearly 25 years. 2. The mwnbet of wpAoyees in go\6 mines in the Province of Ontario varied greatly during the period 1926-1953 (Fig. 1). The Recorded for pofelkarion May 2, 1955. average employment was about 15,200, and it ranged from nearly 22,000 in 3941 to as bw as 11,000 in 1944. In addition to the changes in total employ ment, labor turnover makes for lack of con tinuity of history obtainable from annual ex aminations. It may result in complete loss of contact with many who leave the industry, unless and until some of them may return claiming silicosis which developed in the interim. It is perhaps fair to say that approximately 70% of the total employees in gold mining are engaged in what are designated as dustexposure occupations *; this number includes The Mimog Act, Ontario, Section 355, reads to part, a* follows*. (f) "Dust exposure occepation*' shall luetn, fi> enploymem onderfrouad irt a wine. S1UC0SIS IV CANADA all underground workers as well as those (A) Before a final certificate is issued, working to crusher houses, in milling, and after two years' employment, in the assay office. "to he free from tuberculosis of the A recent survey of a number of gold mines respiratory organs." operating in the Porcupine Area of Northern Thereafter the certificate is kept in good Ontario showed that among a tow! of 3757 standing only if annual chest examinations, employees including x-ray, are submitted to by tite PerCeaC bolder. tm W Mo eteptor** ter tec** tbao 30 *ii h*& tea tit uto*} tajj*l07iTiit for 10 w U ran................................. a.) There is, in consequence, a complete chest XhUistory of every man employed m a dust- *00 b4 bees eeaUBeiQ? easpiojed tor l& to yr.............................................. CM Iti4 boas enUesUJf envforM for sex ittt, uyecn.............................................. iti exposure occupation, conunenciog with-his preemployment examination and continuing MS with annual examinations during the com VW ' 190 plete period of his employment, the films . Despite this discouraging approach to the subject, I believe that nowhere in Canada is there as much factual information available on the progress and extent of silicosis as may be found in the mines of Ontario. Some ap preciation,of this can be conveyed from the following facts: I. For all practical purposes, gold mining may be said to have commenced in Ontario in 1908. For the first 20 years no special attention was paid to chest examinations of employees, with or without x-ray. Com mencing in 1928, however, the Mining Act of the province was amended to require that every person employed in a dust-^xposm-e occupation in a mine must have preemployment examination, including x-ray of the chest, by an examiner appointed for the pur pose and must be certified (a) Before a preliminary certificate, is '* issded are all retained in the files of the local exam iner of the Workmen's Compensation Board of Ontario, together with a card record o! these examinations kept up to date annually or oftener, as intermediate examinations may have been indicated and carried out. 2. In Ontario, the Workmen's Compensa tion Board operates as a semigoveroment function. An independent board has been set up under an Act of Parliament and is em powered to pay compensation for industrial accidents &ad to assess the employers the full coat of same, to Include not only compensa tion but also medical aid and rehabilitation. StUcosk was made an industrial disease under the Act of 1926. The Board's decision on all claims thereafter has been given to the employers, so that the Ontario Mining As sociation, an organization of these employers, has full information on the ultimate disposal of these claims.^ Further, the Compensation Board has been able, through the cooperation , "w be free from diseases of the res* of the Silicosis Referee Board and, in par piratory organs and otherwise fit for ticular, of Dr> A. R. Riddell, a member of employment in dust exposure oc that Board, to set out the year in each case cupations" ; in which silicosis was first deemed to be present, (it) emptaym&rt at the surfaee of i mine tit ore oc rock crushing operations where the tA paper, *"Thfi Prevention of Silicosis in * ore or rock is not crushed in wafer or a .. tbenficak solution which constantly keeps it ' in a moistened or wet condition. (fVi) employment at other localioits. as desig* , nated by tlx* Chief Jmjwctor. at the surface 5 a tmvi or m a pit or Quarry; Ontario Mines,** by N. F. Parkinson, read at Timmins hi January, 1951, and published in Proceedings of the McIntyre Research Foundation for that year, provides farther detail respecting the position of silkosis and the measures taken in hs prevention. 57 y t . PARKINSON . ?ab&s l.--dumber of Case* by Yours m Which Siiiecfix, os Dtfinsd by ike Workm's Compensation Act* First Occurred f {Tahte Includes Avenge Atpt, Awage Dest Exposure, and Number Who Had Died u End <*{ M&> Tear i&............. rnt................. iate.................. use.................. im.................. iea?........... ........ IVA............... . im.................. JWi.................... 28%.................... ran............. . 2S5S.................... vm................. . mo.................... sso.................. .......................... ......................... IftM.................. IMS................... UM.................. Hi?.................. IMS.................. mo.................. we,,......,,.2*3.................. U69............... . law,.................. Total*,... Caeca Of fitUN'tt, Ne. Avcracs M, It. a? 131 .T ti Uj tti ns 48.4 tos ns *03 <U ISA tt.4 OA K.7 tt3 too as 60.1 S* 663 M4 *3 663 *S6 ..... *1 A*n(< Dutt EspoxQR, tj.l fM ......... J IB ouuv OfrUrf Octario 120 !.< os S3 US 1.? IS.? OS 324 ts J?S 13 16.1 M 7BA OS no 03 n.? 1.0 ?<U 0/ n.t so ISA S4 30.1 ' so Vt 1.? V3 IS ies S3 US 13 113 13 tt)1 33 193 03 9JJ> 14 2M 03 ns 1.7 mU S<.7 IS K4 14 *.3 0.1 ---- -- IT. IS Who gtarud After I92S.I N, e 0 0 0 s 0 0 0 g t 2 0 1 t 3 * 4 0 7 t 7 3 7 1 0 l *s Worltm fkad tX Ed Of JHA No. 120 a SI B a 23 19 IS 4? 11 a H je a 28 39 29 M UV i S 21 e 8 0 s t 3 * nuiot * fiwoett wodlifoo el the Jb* au&etaBt to protest teMcoiag s*p7 ! *rt MOMd fry the toftl8Qoo o( aTiW* CM'-'' \ He i*t> U % bi* \a Cm kenaMend to C*ve developed a)\ieotit b detenu's*} by tl* SlUeou* Betew Boert of Ontario Mostly after physical e*0foauo sod ytudy { the ncotde od cha*t xr*y of IbexoaB eoned. tfioee tfi] at work *ad eot yet eligible for eompeautioa are latfodsd, at *n afro peraesa bow Heimj Cere bees aQoved ttUf dealt* l Arei.st Uote epPt Ut dueteapoeuw t**vp*{Jaa up to the tts* or dmloptB* Cttfsfr, ae determloM frog, tb* ouploym' worts aod ffifonnalfon btstted fmai the atas hlsaeeU. I The atteadiaest to We Wntn* Act, suJiot toelnn rtane\ duet eftmioatwa* asd eenffratfoe tot )! uea workJ&x a dw-erpoaurt oeRipatkw* a she adoiag taJoMry of Caterio, earns toto (oree so Jen. 1, u AVAILABi-E INFORMATION OK SIMCOSJS IN ONTARIO MINES in the Province of Ontario, roost of the cases of silicosis developing in the industry have coewft (row the goid-mimng group. Of the total of 1146 accepted cases shown in the accompanying Tables, only 128 have been allocated to the mining of other materials than gold (Table 1). 38 Note particularly Column 6 of Table 1, which shows the number of cases included in the total of Column 2 who started to work in the mines after 1928, The significance of this group is that they all received preemploymeet examination, including chest x-ray, in accordance with the requirements of the Act which became effective on J&u. 1,1929. -j^ silicosis *v Canada rt * workers have ail received at least annual <w5t examinations, including x-ray, over the whole period of their later employment in ' the mines. It is worthy of comment that, of the total of 1146 known cases accumulated in the In dustry from the time of commencement of mining activities in the early 1900's, there have been to the end of 1953 only 45 men who commenced mining in 1929 or later who are known to have contracted silicosis. One must not become too enthusiastic about such a showing, as the final story on these cases I will not be known for some years. There are bound to be additions made to the number of those attributed to some past years. There will be some men who, silicosis-free, left the industry for a number of years, then devel oped silicosis, and sought treatment and com pensation. These men are fully protected under the Act. If, as, and when disablement may develop in the future, provided that they were actually exposed to silica dust in their employment in Ontario for periods amount ing in all to at least two years preceding, they arc entitled to compensation. To permit a more graphic demonstration of the trends, some of the figures in Table 1 have been grouped by five-year periods in Table 2 as follows: An examination of the data in Tables 1 and 2 provides some interesting indications. The number of cases has shown a marked decline since tlte period 1941-1945, If, for example, the number of cases develop!ng in 1954 and 1955 are the same as occurred in Table 2.--Consolidation of Some Statistics on Cases of Silicosis Contained in Table 2 into Five-Year Period Croups (2926-1953) Pfr*- Year J^rtoC Cwerol* Xo. 1MOOBSO............ *M MSM9S5........ 132 wa&ims........... m mmms........... m> m&iaw.......... iso JSSMfiiflit ToUU........... J MO Awr8* Ost Ei9C5UK.Tr. Arfnrfr r......--"i4......... Ace. ia Outdd Tr. Octarte Ostaric 06 18.1 J,7 C 176 16 *0 9 164 *6 <$R 16 tO MS MS IS MS tS 16 Str 114 IS *Tei7r period. each of the years 1951 to 1953, the figure for the last five-year period will be 72. We can he almost certain that as years pass more c%$es will be added to a number of these prior years, but the trend seems efear and the decrease in th*e rate of produc tion gives all the indication of being sub stantial. There is no uncertainty about the increas ing average age at which the new cases of silicosis arc developing. The trend is sub stantial and steadily upward. In less than 30 years the average age for the development of silicosis has increased by approximately 36%. Also there ts no uncertainty about the gs-eat increase in exposure time required to produce silicosis iu Ontario mines. In less than 30 years the dust exposure required has been lengthened by more than 60%. No special reference has been made as yet to death cases, as shown in Table 1. A special study of these has been prepared, which demonstrates certain other trends of interest than those disclosed in a simple list ing of the number of deaths as at the end of 1953. One feature of interest is that 11 of the 12? men wlio were found to have de veloped silicosis in 1926 or before were still alive at tlw end of 1953. The 623 cases have been grouped under certain classifications and by five-year pe riods in Tahle 3. A review of these figures emphasizes some trends already noted and indicates some new ones. The 1946-1950 period shows the occur rence of 162 deaths from silicosis, while in the same years (Table 2) only 136 cases of silicosis were shown to have developed. As a matter of fact, in 1947 for the first time since 1926 the number of deaths occurring among silicosis cases was greater thin the number of new cases developing in that year. The comparable figure for the three-year pe riod 1951-1953, when 98 deaths occurred, was 43 cases of silicosis that developed, as shown in Tabic 2, The age at time of death shows the same remarkable trend upward as the age at which $9 PARKINSON Tarls ttwtibtr fff D*6*kt Ame*g Persons trilb Siliceru by Five-Year Periods (1926-I9S2) in Which Deaths Occurred peerage Age, Elap*rtf Time tram SiHc&sfi'lo De*i+v nod Proportion of Total Death* Due to Silicosis or Silicosis plus Tube?miosis} TiteYter Period Sre-KBi................. 3SQ.TO&................ 1*64*0............... 1804*0..............., iM&use.................. tea-s*u*. .... No of Deatte BO its M* let se TeCals..,,.., ttS Attrage Ate *5 BeaU>, Sr. lU *7.6 W.5 ms BJ 'Ll III M4 AtoUl itiepeeC Time trom 304*6*5* to boatA. Sr. DeeUU f*vo SOtewte tad SflltotM ITeberea* totfe. ferOrat S.O Hi 64 ai tl tSS M ttA }j 68.0 1! 664 8.1 fij `Tb&e-jetr perU>6- silicosis develops but exaggerated here by the fact that the length of time eiap&tg be tween the development of silicosis and death is also increasing. Elapsed time between silicosis and death, as shown in Column 4 of Table 3, has in creased from an average of 2 years (19261930) to 11.6 years in the period 1951-1953, or by nearly six times. Age at time of death (Column 3 of Table 3) increased for the same periods from 44 to 62,2 years, or by 4J<&. The last column, dealing with the. cause of death, shows a marked trend away from tuberculosis as a governing factor. Actually, in Ontario mitring experience, silicosis of it self has never been an Important cause of death. Of the total of 623 deaths shown in these groups to the end of 1953, only 18 have been attributed to uncomplicated silicosis. Zb a number of these, especially where compen sation payments have not resulted, the diag nosis might be questioned. Some interesting research work might be undertaken to determine the reason for the treed here shown, but there would seem to be two outstanding causes which might be considered to have influenced the situation. They are as follows: I. After men develop silicosis, they bow live for nearly 12 years instead of the average Figure 2. 0 SILICOSIS W CANADA of 2 shown in the early years. This means that they have nearly six times as bog to live and, therefore, six times the chance of dying of accident or some other disease or cause not related to their silicosis. 2. The work done under the auspices of the provincial government in the field of the prevention of tuberculosis has brought about a marked change in the position of this dis ease. Mortality rates in the province in 1930 on account of tuberculosis were 57 per 100,000 of population. The comparative fig ure for 1953 was seven. On the assumption that prevalence has been similarly affected, the opportunity of our silicotics to become infected by contacts has obviously been re duced. On the subject of age, Figure 2 shows the percentage of cases 60 years of age or over making up die total deaths of our silicotics in each year. Using averages, it is apparent that there must be a fair number among those whose deaths occurred in each year whose ages were less than and greater than the average figure shown. The graph, however, again substantiates the trend toward greater age at time of death. For example, in the three-year period 1951-1953, of the total deaths 55% were among men over 69, 37% were among men over 65, and 15^ were among men over 70 years of age. Actually, with the average age at which tbe Ontario miners now develop silicosis-- 56.5 yeats (195M953)-and the average age at which death occurs in the same period --62.2 years--silicosis can no longer be, if it ever was, looked upon as a menace to our youth. While the comparison is obviously tiot a fair one, it is nevertheless a fact that the average age at death of all males in Canada as per the census figures in 1951 was 56.4 years. 1 would call your attention again to Figure 1. This shows the mine population from 1926 to 1953, inclusive, with subdivisions representing those employed in gold mines, nickel-copper mines, and all other mines, respectively. All other mines include, in the main, those mining iron ore and the silver- cobalt group. Superimposed on the popula tion figures is a graph showing in each year the number of cases of silicosis taken from Colrnrm 2 of Table 1. The mere statement that 1146 cases of silicosis have been found in the mining in dustry of the province gives perhaps an erroneous impression. The length of time over which these cases have accumulated is of interest. Of these 1146 cases, 1018 have been attributed to gold mining, in which there has bees an average of 13,200 men employed per annum for a period of some 28 years. StmMASY 07 ONTARIO MINING EXPE81ENCE From the records certain obvious develop ments have, I believe, been demonstrated, as follows: 1 The cumber of cases of silicosis developing each year has bees deereasing at a rapid rate. 2 Tbe average age at wbich silicosis develops has Increased from 4!5 years <1926-1930) to 56,5 years 0951-1953). or by 36*. 3. Tbe average number of years of dust exposure required to develop silicosis among the few who contract the eoitdirioo has increased from 15.4 years 0926-1930) to 24.8 yean <1951-1953), or by 60*. 4. Only 45 cases, or Jess than 4* of the 1146 known cases of sllkosls Is the Industry, have occurred among those who commenced mining after 1928. 5. The average age at death has increased from 44 year* (1926-1930) to 622 years (J9SM953). or. by 41*. 6. Life expectancy after silicosis develops has increased from 2 years (1926-1936) to 11.6 years (1951-1953), or by six times. 7. Tbe proportion of cases that died of silicosis or silicosis plus tuberculosis has decreased from 91.8* (1926-1930) to SS.l* <1951-1953). That these developments are of importance to the men employed in tlie industry and to the industry itself needs little emphasis. They have not been achieved without effort. The most important dianges that have been made since 1925, when silicosis was recognized as being present among employees in mining, are briefly summarized as follows: 1926 Silicosis was made ao industrial disease for compensation purposes (at industry's request). 61 1928 Legislative provision was mack for compel- torr pnxsafilojB*Di x-ray examinations and certification tot dmt-exposufe occspations (at industry's request). `` 19ZS and continuing , (0) Putt prevention. (b) Post collection. (e) Design of machines to avoid making dust Improvement* in sttae ventilation have beta available factual information in the form of x-ray films, listed results of physical and x-ray examinations, records of dust exposure from the mining companies, and decisions of the Workmen's Compensation Board of On tario over the years as to compensability on account of silicosis of die persons concerned. There has also been avat&bk (be expert such that tn many mines a greater tonnage of air is sow pumped underground than the tonnage of ore touted. 1944 Genera! aepiicatioQ of aiomiiwtn powder projfoylaftieaMy in Ontario gold fmnet The miftes would like to be able to a&stss the value of any one of these changes ia the over-ail wprovemeot io the silicosis situation as demonstrated. The Jong period of ex posure required to develop silicosis and the practical difficulties in setting up controls make such as appraisal at this time difficult, if not impossible. We are satisfied that preemptoyment x-ray examinations, practiced since 1929, are im portant We are satisfied that the control and re moval of dust, together with improved ven tilation taken is hand in 1925 and worked at assiduously since then, ate important fac tors. After nearly 30years, however, silicosis has not been entirely eliminated. In the light of the more rapid improvement *m the silicosis situation since 1946 (Tables I and 2), we are satisfied that aluminum pro opinion of members of the Silicosis Referee Board oi Ontarioas to tht date when silicosis as defined in the Act first made its appearante. In these circumstances, the story of the history of the known cases of silicosis that have occurred over the years may, for all practical purposes, be considered factual. To use this material, however, in assessing the position of silicosis vn the rest oi Ontario, let alone in the rest of Canada, raises real difficulties. Io no other, area, nor among any other group of workmen employed in a complete industry, of which ! am aware, do any such records exist as have been available in the preparation of this material. First, in Ontario other industries than mining have their silicosis problems, and while dust exposure may is some be severer than that found in mining, one can be sure that the gross amount of silicosis found its all such would be only a fraction of that found in mining fey reason of the great dis parity in the total number of employees. phylaxis administered generally to all goldmining employees since 1944, demonstrated to be effective in the prevention of silicosis \d animals, may have been a factor, SILICOSIS JN TSE REST OF CANADA Omitting references to provinces where mining and other forms of industry involving More time will be required to demonstrate the actual position of aluminum prophylaxis in this regard, but, in the meantime, after exposure to dust arc not found on as com parable a scale as io Ontario and where little, H any, silicosis would be expected, it has been some II years of continual application, no found that in 1951, for example, the propor cases have arisen which demonstrate or even tion of tbe total Canadian population in On indicate any ill effects. tario and other provinces that might be SILTcosts 1N ONTARIO XRO* OTHE* rsnUSTMES THAN miNINO In preparing this review of silicosis in the mining industry of Ontario, there has been 42 classed together was as follows; p cm Osuto.............................................. aj,g .................................................. o AJbSIU............................................... *.? BrUUb CoWmBJ*.................................... SiUCOSJS JJf CANADA Oa the basts of the actual value of mineral production, the csrrapcrtxJfog figures for thesejtfovinces tn 1953 were as follows: PrartMe Per that Ontario................................................ HZ tyMtae........................................,........ HA Alberts......................................... . 1U . Britt*.OotafiWs............................................. *J tzddag more definite information, it might be assumed that the production of sili cosis in these other provinces bears some comparabfc relation to the figures covering population or value of mineral production. 1 As a check In part to estimates made on tie Sasis of any of the above figures, the Workmen's Compensation Board of the BnridDce-of British Columbia for the year &ded Dec. 31, 1953, reported that, during the 18 years since silicosis became a com pensable disability tn that province, 616 workmen have been gives compensation for impairment therefrom. The only comment l would make In this regard is that, even thoi^h some of the 616 cases arose through other industries than mining, the proportion in relation to Ontario mining cases seemshigh at about $4$ of our 1146, while their population j$ just over 25% of our Ontario population and their value production of minerals about 35% of our value production. Unfortunately, I have no similar figures to give you ott the situation in Quebec or other provinces. Assistance m the preparation of data was rend ered by Dt, K R- Riddell and other members of the SibeosU Referee Board of Ontario. COMMENTARY ON REFERENCES BY N. f. PARKWSON CONCERNING ^UOOSIS PROBLEM IN ONTARIO ANACSW t ttO&tL, AU,, Wt*.Ga*4* to h awiisJ examination tor ccwpensatioo pur poses, each has been under periodic cxdkat super IVt, VUK" vision. Mose have had periods of observation sod treatment In sanatoria or general hospital*. All Ur. Paridason has asked me to enlarge on some the deceased have been autoptied. Thirty-four of features of the mining situation and, b addition, the miners ate still living: eleven have died. to say a few words in regard to slicesis b indus Some of Use important data cm these cases are tries ia Octane other titan taming ia which work men encounter silica dust. feted i Table h All the miners in the group developed silicosis We are advised that !1S4 per&oos are knows rapidly after periods of dust exposure which were, to have cos&aned riikoris in tbe Ontario mine*. on the average, about half the period given by Forty-five of these entered the Industry and, as Ur. Parkinson as average ,lr mines at tbe gar as b kaown, were first exposed to silica present time. Evidently these Persons vert especial : after 1928, when the preeroployment examina- ly susceptible to injsry by silica. Ahbough tuberev- 'it' prospective miners was tostituted. This fouf* isfeetioa may not orpfefa ihe s&eeptibilitf is resents a very small fraction of the miners all these cases, it appears signifies"! that 28, or Wto soaa&en&d work to the industry after 1928. slightly more than 60% of them, were definitely ir?^dev&ped the disease in -spite of; greatly;; suffering from- tubrivulosk and that to 8 others, CJ - - S_______> ______. 4.M .' L '..........................._................J -i-i_______ V -The medical records on each of these cases are, - tuberculosis. Rather are (her am* < tvbecmby i7 :Btt0!ete< They include clinical data and^riKeeib. Tbe term' em tp have considerable f'lSbl '<be$t radiograms prepared at die time ehrierit,.Most N thza'aus are not overtly tubercu- ttfceraered the fndusrty and at yearly hUrrah}.'' kms wben first sten', Neverthetess, ia out experi- duriM^s'emptoyment there. Bach miner m thej'. >** tuberculosis should always be suspected as .Staa filed a claim with the Workmen's): * factor in cases ib develop quickly after short ex- mtigu Board, in cotuiection wife which bt!r posures or b those to wWch toe pulmonary fibrosis w^fuffiSr. examined and x-raye*/: Subsequent continues to progress tatg after expose has m-r^r inf'* ' ceased. Silicosis and tuberculosis are peculiarly . -'Rec&fded for pbbkcatioa June 2Q,39SS. . related, This should always be kept in mind by ! Dki&xi of-indcitfiai Hygicsz,-'$)*pkrBaeM oS Jbose concerned with the medical selection of Keahh.dor Qwarito.; persons for exposure to silica dusts. A- review of .. .. . *, &: L T: 63 RIDDELL . Ta0L 1,--Daia cm FortyFrv* Cases of Stikotit Contrasted in Ontario Mints Hibtn (A TUbcmioiJi <*;., Whole Oreup lltun *tth Suapected TNaWraoJeaM* B feUtrnwrasADpnelf Fiw A*** Owaanowa>*Bt ( kmiii)** Tr. Tvt&t**-.............. Oldat......... .......,. 44 Awrare, Tr. .... At* Wbca tlnl fiJliMUe, *r. TwouBeat............., tt OJOeat-.................. td Avtnf*. Tr. A2A .... gxpeaurv. St, Sbortcst................. i j^otesL...... ........ n Av*re*e, Tr, ft.? Evatba AT* it Tr. are * w&fcb AAe Wna Exaoawv PIm Oon&MBeed, BUkoUe. St- Tr. Sxpotan. Tr. CaoM ofDestb as n rt ts Polwoaarv eubemtfoeia u ma 4 BewHbotmW mfi&om*; aQ*c cubreuloJt ae .. B *4 IS Pul&ootr? wUrentoaSa 1 ,> m *6 It ..Loaf l&iuct t&flowtt* otmiaoe to* tsUBUStJ atwtneeties; so eabemuos S B U t ' Pabsoaasr fcrcnlc*li M s' s to 41 * 00 3 a n n at B 0 ts 44 49 46 n *. 8 u 21 U 9 Srejh&otoak autlaosts; Q*e toWroJota Blrfat beam Mw*; eor pobnoBiie; otooJawot VoMT^^SakSS Fufcaesar? tabenadoria Potar&Biurj tobermJMl* PntnafthSTT tsbecolfaUa OorSsoiaa fevolrta* sacrum; so tuMmloaU * Net <fcSawiy datftnbsd. medical data sod the.aerial chest radiograms oo this few? of cates auggestt thii,wsTve oJ toe persons 'concerned were poor risks /or exposure to silica dust at the rime they were hired. Our irtfomatieo in regard to fee silicosis situa tion in Ontario is industries other than mining is, at best, approximate. Until the SStcosb Act of 1952 was passed the records pertaining to this matter were imperfect The institution oi pre- empkjyment exacrinatio of candidates for employ* mem m most industries cohered by the legislation and the periodic examination of workmen already employed, as is required by the Act in certain industries, has added to our tn/onoation, but some time must elapse before cur records are built up to the point where they are of much value. Even as thing* stand, our records have some vaktt, however, Pvfcr to the passing ol the Act, many workers in these industries bad been exam- joed by the Division of Industrial Hygiene <4 the Ontario Department of Health. Begfening in the early 1920's, surveys were conducted in many plants where workmen *r exposed to sUka dust. From 1940 onward, periodic examinations were in some of these plants. Unfortunately, the examina tions were conducted on a voluntary basis by ar rangement with the managements of the participat ing plants.' As*they were done at irregular intervals, the coverage was not complete. Compensation claims Also have supplied considerable information 64 For many exposures, however, the period covered by compensation das&s dates back only io the neighborhood of 1915. This source of information, therefore, has many limitations and is not as useful as it is is the case of masers In Tables 2, 3, and 4, which follow, information regarding uticotU in these industries is displayed. The data contained m these tables seen to war rant, insofar as the Ontario experience is concerned, the Softowfag conclusions: Taslf, 2^--iJirtribvriow of 57$ Known Coses* of Sykosisand Other Occupational Pviptonory Disrates p* Certain fioserdovs Industries in Ontario Indoatit Worker* io SAypppormoxr,e, Work*n vicb W8UosUbHen Wor*. bo. No. Ns. Toundrv . ................ p ttt 436 <JrMM eottioe........ . SCO rt so Poreolab ind pottery mau<eu*rtn* ........... tia ss 63 Bfiks b?ti msHa*. <te... B IB kacti2&aotu ................ uco tei to *Tbes rre stiy !; in Jeousrr, is*. tloefodee sUieosts ud otber tones of p&uusnOeouJaUs. I, Many persons wife wticosis can continue in gainful employment in their accustomed occupa tions or at other suitable work, SiUCOSJS IN CANADA Taslb X--Analynj of 3S6 Silicosis Cbme* 4ver*ff* Artrue AreWbea ilit xoofee Gmumsc* Avenge Are After CJ*t cams et Woee Flm intc iM4utt*r Vo. riled. Tr. Ecposcn. Tr, BLBcetfc, Yr. Sxposwe. It. tomirrwctUn..................................... tj* tAS as MS MS Sum cotters...................................................... is S7S ns MS BtJ Pomrfofri sal panes? u sea *ts as Htie* brte* hMOdkm..,............................. K tit S&4 U.l ttt Oater eerestie worker*. ataers. trflndera, W. 1 fit* aos OS IIS of ahnufee peuden t............................ t tii MS MS us * Tbew penees bod fifes tfelaa for 'works**'* owmbjsUob sad won life* wbea the oostpezttOoa *u node. * Ob* had mao' oxpowm; ofto ttt* com esnJUed, tbe avenge jeon of sxponn wn 8S joan. Tails 4.--ifortstiiy Statistics for 385 Deceased Persons ttitk Silicosis from Three oi the More important Exposures* Zzutasttj Poeedrj ................................... .. dntatc* ud sandstone *om. Otfwafc fodatriea........ .............. No. m SB AmwtAfi t Death, Tr. as W.7 StS ATtntit Jfcrpoaore, Tr. CL4 B.T MS . Astoptiea MI oeadoeurf cut oUgbtiy mot* tfua B% of tteM eewu. Dmtit* Oootribeted tAbjStiiwfla an, aaetotfiat MX* due to tt*. SBA, fododf&r Mt% due to the. no, tododtar BLO% doe to foe, Z Tl* iaddcsce m most irrfustras Is wbkh workers sseouster silica dost m Ontario is not high. 3. In gmni, exposures m which casual later is used ait severer *h* art those ia v/tucb $HJIJ labor i employed. 4. Although silicosis satoetimes contributes to the early death of affected persons, in general it does aot at present appreciably decrease life expectancy. 5. Silicosis is much more important as a cause of disablcoMBt than as a direct or contributory cause of death. 6. TofecrtslcaU is still the most disabling factor and the chief cause of death ia silicosis. From tune to rime inquiry is made concerning the incidence o! silicosis la thd various Ontario expos ures. Ur. Parkinson has explained the difficulties wbkh sufTOuixi any attempt to arrive at a reliable incidence rate for the mwg industry, in connec tion with which records covering a period of more than 2$ years arc available It is even more diffi cult to determine incidence in other industries. You were advised that no records comparable with those for the mining industry are available in these in dustries. In industries such as the foundry industry, labor tgrn*ever is high, and ftoetuttson in piodoction constantly afters the number of persons In employment- The majority of foundry workers in Ontario who have contracted silicosis entered ex posure early is the century. Some, in fact, began foundry work in the late JgW's. In a few instances, exposure had occurred in Europe, m the United States, awi elsewhere, as well as Ontario. Spe cial difficulties arc encountered In regard to the granite-cutting industry. A large proportion of the Ontario eases from that industry occur in persons who were initially employed cutting stone in Aberdeen, Scotland, or in Barre, Vt It is impos sible at this time to deterau'se which exposare was the more important. Where so much is unknown and not obtaioabk, inridccce rates have little moan ing. Mr. Pnridsson's observations in regard to the present situation In the Ontario raining industry, particularly that branch concerned with gold min ing, are very encouraging. The improvement that has occurred during the period under review war rants the belief that further improvement may be expected It cannot be looked for, however, unless the preventive measures now m force are continued and vigorously pursued. It is out hope that over the years the control measures recently instituted in Ontario m respect of the other silica industries may prove equally effective. It has been a pleasure to contribute something to the discussion of this very interesting paper. DJUp. neumoconiodU MORRIS KUINFELO, M.O. JACOUfLIKf MESS1TE. M.O. ead WVWS K TAMRSKAW, RD., Ne York Since Tborei's original study in 1896,1 when ttlc pneumoconiosis was first recog nised as a distinct pathologic entity, numer ous clinical and experimental reports have continued toappear In the literature. The bulk of these reports have related to workers in tak mills and mines and to those engaged in the rubber industry.* Three investigations of the tak industry were earned out in New York Siate.f Drecssen's study of 57 men ex posed to tremolitc revealed an incidence of . fibrosis above average (67%) but of a non disabling character. In contrast to Dreessen's4 observations, the findings of Porro, Patton, and Hobbs,4 based on 15 cases with 5 postmortem examinations, showed that pneumoconiosis causing disability and death does occur in tak workers and that patho logical tissue changes are principally due to talc itself. In 1943, SiegaJ, Smith, and Greenburg 4 reported on the dust hazard in treroofite tak mining, including roentgenologic findings ia tak workers, and their findings and conclusions were similar to.those of the latter. Since the roentgenograms and histories of the 32 cases reported on by Siegal and asso ciates* were still available after 14 years, a follow-up study was undertaken in order to (1) ascertain the health status of this group, (2) evaluate the present operations and dust concentrations of the talc mines and mills. Records far publication April 6, 1955. From Division of Industrial Hygiene, York Stale Department of Labor. References 2 and 5. t References 4 to 6. 66 New and (3) do a comparative study of the work ers employed before and after the newer engineering techniques had been introduced (1943). The present paper deals largely with the first two objectives; the third is now in progress and will be reported at a later date. FINDINGS Environmental Data.--A study of the operations and dust concentrations of the talc mills and mines at this time shows a marked improvement in the engineering techniques from that found in 1941, and this is reflected in an appreciable decrease in the dust exposure From 1943 to 1948, a number of corrective measures were insti tuted to reduce the dust concentrations and included the following: (a) wet drilling in mines; (b) enclosure of elevator and chutes; (c) Installation of automate bagging ma chines; (d) conveyorized car loading; (e) discontinuance of blow rooms, and {/) pro vision of local exhaust ventilation. The dust concentrations obtained at the mills before and after improvements were instituted are , summarized in Table 1. Medical Data.--Deceased: Of the original 32 patients, 19 have since died, and the causes of death obtained from the hospital records, physicians' files, or death certificates are given in Tabic 2. No necropsy data are available to confirm the clinical diagnosis. The ages of the 19 that died ranged from 48 to $4 years, and in the 4 whose cause of death was believed to be due to pulmonary failure associated with tak pneumoconiosis, the ages varied between 60 and 79 years. Living: Thirteen of the origins} 32 are still alive, and of these 7 have retired and 6 arc gainfully employed. The ages of the re tired group vary between 63 and 83 years; the ages of the actively employed, between T u ll' V i PNBiryfoccwiosjs Table 1/--^TMi^omfnv CM Cwl* 0a*a ai SovtroJ Nnr Ker* 7*ic Atfw *d KBB PrgHaf..................................... Mem*.................................... Omni *tr............................ Mill. QnuhOit .................................. 8em&&f ............................... 11rt**>nv Tft'Ba Gum um epmtoT*,,,,,, .... BtXtU* ................................... Blow roea ......................... . O&B *W*4 ...........-----OcmnI *4r .............................. La* tt Ortxtoil flMji (mx> H*&em Bitb l?W1 418 tfi* 47S * 8U ISO as * 41 IS n us aj* ss w W> IX sn m m M& e iso * 2* ijyr US CO reD9W4p SCadx 0*0 ' La* SteOssa Bifts 4<erut 0t s4 .. 8* 44 - S U BO 4 ts 6 ) t 9 si 14 so HKSAUOQte DlwmUooed s IS 40 * ST m n a n ' Dost coasts re b tpffltofi crotte) coMc toot, i BIB 40001 dbs to btUf vso c*TO?or codon*. Tablb Z--Causes of Dmh in Tate Pneumoconiosis Ftttm Ar,tr. *,.A. 0aBrs <2. B. a W, B. D. M a.a a. r. a m 4.0. ,i. to.t fi.L. . V, ObSmbb a M M Ofilsovs Coo* of DeMis* F7*rtrl tkuO Ctnteoma ot X Met (1> Bypertea*)** **tte***I*T <im*m <*) Ootbm bSMTAuc (I> Oatbrt! ttcaerrhf OS GMr*t orwrtowtoroiio 0? PoSaoncrr Io*nci07 > CootcstJvc b**rt *aun Bataowfl AcEM ByocortUl tBtartOoo Scott mroecnHiS Ofcrwiea AeQtt B70CltQ*t tttarrttcai attootWaoioc of pSeoro--pa' noctoioiia CbOounO} Fctfett ACC.Tr. P * Cbbcc of Scatfi* 4u mro**rtJl toJatrUoD Oucboaa o< ctopoefe ClKttMU* Ot pATKAnC BalaoBaJT JoOvre usodiud who pncatoo<oDlotB SaodcoiJ aloe FuimonotT taflarc 4u to pseaaioeofuocB 0> SBeutDocoaiocN d> UyoesKitis O&ksowo OsrdDOtsa of OX trt * CtM of decth wott oou&Md tress the io&owttt ootawn: OJ prtr*U pfewMcw; OJ Sottsi ntoros, one (Si &XU* 45 and 64 years. A summary and analysts ol the clinical and laboratory findings are seen in Table X comment In view of the comparatively small num ber comprising this investigation, no signifi cance can be attached to age incidence of the deceased and livinggroups. It is noteworthy, however, that the age range in the retired workers was between 63 and 83 years and that in the four deceased, whose cause of death was believed to be due to pulmonary insufficicocy associated with tatcosis, the ages varied between 60 and 79 years. Al though no statistically significant correlative data can be formulated between the duration of tremolite talc exposure and longevity, it is of interest that an above average life span may occur, following prolonged exposure to talc dust and associated with pulmonary dys function (Tables 2 and 3). Analysis of the medical data of the living shows many similarities to those reported in the litmture.t Clinically, the outstanding features ape dyspnea, productive cough, ab normal chest findings (diminished breath sounds, basal rake, limited chest expansion), clubbing, and a roentgenographic picture de scriptive of pneumoconiosis. Gimcaffy, the course is relatively slow but progressive, and, similar to silicosis, the clinical picture does not retrogress with marked improvement of the industrial environment or upon retire ment. I>yspnea is present in ICO$ of the group and is sufficiently pronounced to limit ? References 5 to 7. 67 jUT-- jy lU S* X x a X x a% X a*S 3 ava>- * ** J5 a 2 gg f$t f&t 8 '8 84 6+ 4 *a $.a c ^ ? * e Q 6 9s 2 * ft X zs |S |e| i i ?g Si B* ' liif te a CD ss ss 8 a aM . _d w . i is Si Si a aS x NHt ii If esss | 8f Sill I?IIa!*I1t?js5o 32 gs 4 Si ilfiS If _.IBil<lS I*2" I I 35sUKs iIlIlI | 11 s ||| !|| a 6 ?! ifI ?a a IHIII le1|l IIIIII IMII lUi eI Mil1 *:a *3E ^Ig t BMW RBM CM 0 8 CD * Xa a se b, (h *e. e, S& a, 5b, Sb. 4> Sfe, I* .C _ T If I *1 li I s-< c 21 8 A ^B Bs 9 XX ft ft 55 TALC PNEUMOCONIOSIS the ordinary routine physical activity of the worker to a moderate degree Of extreme interest are the findings m the chest x-rays. The bask; lesion is an in terstitial infiltration of variable intensity, located basally and in the midJufig fields and of bilateral distribution, with the apices rela tively spared, la several, the infiltration is nodular is character. Emphysematous bullae of varying sizes are observed in four (Fig. Fig. 2.--A, Pahcrt B, M.. 1941, pericardial and diaphragmatic plaques are seen. B, Patient B. M, 19H, pericardial and diaphragmatic plaques are more proootstad. KLEWFEi.fi K7 AL lA and B}. h tow. striking finding is the presence of opaque densities, varying from single linear strands in the. region of the diaphragm to massive dcpositt^-biyarre in shape, extending over a large part of the lung field and occasionally on the peri cardium (Fig. 2A and B). These deposits, referted to as wk plaques by Siega? and as sociates,* arc observed in. aU but one of the cases studied. Cardiac enlargement is pres ent in four persons, in two of whom the cardiac configuration is suggestive of cor 1941. As mentioned previously, two ol th< present chest x-rays showed cardiac con figurations suggestive of cor pulmonale, bu' of even added significance, a markedly de creased cardiac silhouette is noted in one pa tient (G. S.) and is strongly suggestive in another. The cause for this is not clear. It is possible that pleural pericardial adhesions, associated with the plaque formation, and subsequent retraction and limitation of the pericardium may possibly account for this decreased cardiac silhouette. pulmonale. The pulmonary arteries and branches are prominent in a number of the chest x-rays. When comparisons are made with the roentgenograms taken in 1941, it is of interest to note that, although variable progression occurred in the majority of the patients (Kg, 3A and 8), the most out- star.dmg revelation is that wlwt in retrospect had appeared to be severe pulmonary icrvolve' ment in the original series cannot be so con* sidered in the light of a 14-ye&r interval. Furthermore, the hilar adenopathy which is x seen in six of the present scries in retrospect was also present In.'three of the x-rays in Ko correlation between symptomatology and x-ray findings is noted, and this has been observed fey others.g Although tins series is small, there appears, nevertheless, a trend between the degree of dubbing and chest x-ray involvement; those with severer dubbing show more extensive pulmonary in volvement. Six out of 11 show abnormal electrocardio graphic configurations, such as (a) pattern of right ventricular hypertrophy (2); (b) pattern of left ventricular hy{*rtrophy (2); |Brffices 6 wd S, TALC PNEUMOCONIOSIS (c) abnormal rhythm <1), and (d) non specific T-wave alterations (1). There is a suggestive tread between clubbing and ab normal ekctrocardiograpbk /ladings, In five, whose electrocardiograms are normal, only one shows dubbing, and this to a mini mal degree; in the six with abnormal electro cardiograms, clubbing varies from a moder ate to a marked degree, bang severest in the two with the right ventricular hyper trophy pattern. It is noteworthy that in the latter two, the clinical picture is characteristic of cor pulmonale. The incidence of the latter in tremolite pneumoconiosis is unknown; however, histologic evidence reported by sev eral investigators * confirms an etiological relationship. Jaques and Benirschke * have reported not only generalised thickening of all the pulmonary arteries, with cardiac en largement associated with progressive pul monary talcosis, hut also a granulomatous involvement of myocardium per se. In view of the paucity of the available pathological data on human pulmonary talcosis, the mech anism underlying the development of cor pulmonale >S not dearly defined, The peripheral blood findings are not re markable and indicate that the peripheral blood does not reflect the physicpathologic changes associated with talc pneumoconiosis. The workers presently observed arc well developed and well nourished, in contrast to the observations made by Stegal and asso ciates,4 and no reason can be offered to ex-, plain this apparent difference. The results of the present study confirm the findings of other investigators that talc per se does produce a distinct fibrosing pneumoconiosis, and it has been suggested that this slowly developing fibrogenic dis order may be allied to asbestosis.1 Accord ing to McLaughlin, the evidence favors that talc pneumoconiosis is caused only by the fibrous varieties of talc. The asbestine variety of the tak found in our study may therefore explain the close resemblance of the x-ray picture to that of asbestosis. It is significant that asbestos bodies, first emphasized in talcosis by Gardner, are almost invariably present In cases of talcosis in which tak fi bers are of an appreciable length.*4 This has been observed histologically by several in vestigators* and by ourselves.(| In essence, this pneumoconiosis consists of a dense fibrosis which is particularly prevalent peribronchially and perivascularty and occurs in sheets, occasionally assuming a nodular con figuration ; the latter finding has been sug gested as representing a reaction to the quartz content of the talc. The hilar lymph nodes are generally described as showing no en largement or fibrosis, and on microscopic ex amination they are reported to contain talc laden. macrophages and the tak content to be of considerable magnitude. It is appreciated that some of the workers may have been exposed to a relatively high concentration of quartz at some phase of their operation, but it appears highly unlikely that this was uniformly present for all the workers, particularly in view of the con sistent finding of low free silica content in both the mills and the mines. Furthermore, cvideiice has been presented by recent in vestigators if that moderately advanced pneu moconiosis is caused by tak in the absence of any silks in the talc mixture or in the atmosphere. It is not unlikely that some of the commercial preparations of talc which have different mineralogk and chemical characteristics, as pointed out by Hogue and Mallette,* * may require a long exposure be fore chest x-ray evidence or symptoms ap pear. From observations of Siegal and as sociates,* 10 years are required between ex posure and onset of symptoms. What the specific factors are in the causa tion of talc pneumoconiosis are not known. There is oeed for more epidemiologic studies where environmental conditions are well con trolled and the life course of the worker is closely followed. This would permit a better statistical analysis of data than is now possi ble. There is also a need for further experi mental and biochemical research in this field, and it is more than likely that the utilization of all throe approaches will lead to the cslab* fj Kfemteld. M.: Unpublished data front persotwl observation. Is References 9 and 10. 71 KLE1NFU> ET AI~ lishmcnt of better defined criteria and a clearer understanding of the mogonism and pathogenesis of talc pneumoconiosis. 6. In general, the workers appear well de veloped and well nourished in contrast to observations reported in 1941. Although progression was observed in all, SUMKABY ANJ> CONCLUSIONS the clinical course is relatively slow, and in The health status of a group of 32 talc workers, whose roentgenograms and his tories were available after 14 years, were restedied, and the following data were ob tained. I, Nineteen of this group had died; their agesat death varied between 48 and 84 years. In four, whose death was believed due to pul monary failure' associated with tak pneu spite of the presence of moderate infiltration and pulmonary dysfunction, six of the work ers are still actively employed. The marked Improvement in engineering methods is reflected in an appreciable de crease in the dust exposure. The pathologi cal picture, however, did not retrogress with improvement of the industrial environment or upon retirement. moconiosis, the ages,varied betweep;60 and Assistance was rendered in the present study by 79>years. Ofthe hying] si* are gainfully Or. Jesse R. Patten, of Ogdensburg, N. Y, by employed. ] *Mr. John Kean, Superintendent, and MUs J. .^RUbop, of the X-Ray Department of Edward 2: The outstanding .aiofcal features in *3*ble Hospital, Gcnveroeur, N. Y,, and by our volve the p'uhnonary and^ardidvascul^r sys IadastriaJ Hygiene Engineering UmL tems. Dyspnea aid cough are .'freqiient Emphysema, basal, tales, diminished chest expansion, ajid clubbing are the striking phjr* steal findings, REFERENCES 1. There!, C r Die Specfcstanlunge, Btitr. path Aoat:SS, 1896. 2. Marshall, 6, and Perry, K, M.: Ds. Chest, 3. The characteristic chest x-ray is'thaj of a diffuse infiltration of the basal and midiurig fields, with occasional nodularities sees. Emphysematous bullae, hilar adenopathy, London 2:262, 1952. 3. 'McLaughlin, A. E.;'CHed by Debt. A. T.: Other Lang Diseases Due to Dust Postgrad Med. J. 25:639-649 (Dee.) 1949. 4. Dreessen. W. C*. Effects of Certain Silicate and cor pulmonale are not. infrequent. Talc Dusts *oa the Lungs, J. fndust Hyg. 18:66-78 plaques,;located in>the region of the dia phragm, pericardiunvand **nrfsT>g over a large part of thelusg .field, are consistently observed but do ncit reflect the degree of jial- (March) 1933. 5. Porro, F, W.; Patton. J. R.f and Hobbs, A. A.: Pneumoconiosis in the Tak lodostry, Am. J. Roentgriof 47:507-524 (April) 194Z 6. Siegal, W.; Smith, A. R,, and Greenburg, L.: tnonary involvement. .likewise,.no correla Dust Harard in. Tremohte Tale Mining, Including tion between sym|rfdniatbk>^.and x-ray find-t Roentgenological .Findings in Tak Workers, Am. ings is observed,' : ':'V:V<* ' J. Roentgenol, *11-29 (Jan.) IW3. . , ?t -Mann, 8., and Deasy, J. B,: Tak Pneumo* 4. 'Abnormal echocardiograms.are seen - toasts is die Textile Industry, Brit W. J. 1:1460- in six and include patterns^ right ventticu- 1461 (Dec 38) 1954. lar hypertrophy (two) and left ventricular hypertrophy (two); abnormal rhythm (one), and nonspecific T-wave alterations (one). The two persons demonstrating a 8. Dreessen, W. C, and Dalla Valk, J. Sd.; Effects of Exposure to Dust m Two Georgia Talc Mills and Mines, Pub. Health Rep, 80:131-143 (Feb,) 1935. 9. Jaques, W, ., and Bcnirschke, K.: Pul right ventricular hypertrophy pattern had monary TaJcosis with Involvement of the Stomach other features suggestive of cor pubnonak. There ts a suggestive trend between degree of dubbing and abnormal electrocardio and the Heart, A. M, A. Arch, Isdust Hyg. 8:451-463 (May) 1952. 10. MeLaughlio, A t G.; Roger*, E, hd Dun ham, K. C: Tak Pneumoconiosis. Brit. J. Indus*. graphic findings. Med. 4:184-194 (July) 1949. 5. The peripheral blood findings are not remarkable and do not reflect the changes in tlie pathophysiology of thus disorder. 13. Hogue, W. L,, Jr, and MaJktte, F. S.: A Study of Workers Exposed to Talc and Other Dusting Compounds in the Rubber Industry, J. Indus*. Hyg. & Toxicol. 81:359-364 (Nov.) 1949. 72 \ p tL J<,,Lr Qoll 3uU nettmoconioii6 on gtamer e ertsucK mx, Ockriftt, Oat, Canada (a,fxcj. INTRODUCTION Pneumoconiosis has been a compensable condition in tlse Kolar Gold Field *** since 1940 and continues to be a potential hazard only because up to now, although there may be considerable dust retention within the fangs cf underground workers after a period of 10 to 15 years, little disability is en countered. It does not primarily manifest Itself as a clinical disease in the true sense of die word but rather as a radiological con dition. The potential danger is the association with tuberculosis, which will be discussed The type of mining carried out on the Kolar Gold Field requires the drilling and working of quartz. The quart* occurs in reefs, varying from a few inches to 6 ft. in width, which dip at a sharp angle. Over a considerable length of time--70 years--great depths, down to 9900 it. have been reached and are being worked. At these depths the dry- and wet-bnlb temperatures are high, and the use of water in dust prevention is excluded.f The quartz reef is encased in vary ing widths of lode matter formed from the Recorded for peblicatSon April 7, 1955. Formerly Senior Assistant Medical Officer. Kolar Gold Field. The Kolar Gold Field is situated on the eastern border of M^ore State, South India, in latitude 12* 57' N.Vtd 7ft* IS' .. at a height ol 2895 fu above sea level. adjacent hornblende schist, and these lodes and hornblende schists are composed of stli* cates of A), Mg, Fe, Ca, Na, and K (Kay and associates,11952). The average underground workman is of Dravidian stock. Most of the workers came originally from the North Arcot District of the Madras State. Many of them are second er third-generatioa bore on the Field. They work in the mines throughout the year, except for short vacations, and usually com plete 30 to 35 years of service before retiring. It is oot exceptional to find tnen who have worked underground for 50 years, The usual age of beginning work is between 18 and 25. DtFIKITtOK The Mysore Silicosis Buies allow any man to retire with compensation if he has simple pfleumoOTokwis or to continue at work if he wishes. If be elects to do the latter, he for feits present or future compensation should he later develop tuberculosis. If, on the other hand, he develops the infective type in the beginning, then he must retire, and he re ceives a greatly increased compensation. Pneumoconiosis is defined in three stages: (1) anteprimary--radiological evidence only, fThe rock temperature at a vertical depth of 9129 ft. is 143 F, end the geothermal gradient is 1 F per 120 ft. of depth in deep levels. Due to the sotceornpressioa of the air on account of the rise in barometric pressure from 27 in, at surface to 36 fat at a depth of 9000 ft., there is not coty a reduction in volume but also a rise of temperatutc of 1 F per ISO ft in depth. In order to improve jhe ventilation, the downcast air is dehumidified and cooled, and the volume supplied varies from 100,000 to ZXflOQ cu. ft per minute. Consequently the dust is constantly stirred and kept an-borne. Extractor units at the rock face are used, and attempts arc made continually to remove the dost harard. 73 FFRBNCH classified as pneumoconiotic$4 In the pri mary stage the following may be found; 1. Cci gh and ewld degree of shortness of breath occur ce exertion. In all those cues with marked symptoms, emphysema of bronchitis is present In case* with Ud symptoms, great aggravation ccctifs following secondary respiratory infection, and broflcfcospasm ouy develop. Z Pain in the ehest, retrosternal, unilateral, or tfattral, is olten complained of, but Its significance is no*. uo&mced. 3. Physical tigs* a:e timhed to those with emphysema, .bronchitis, ot tuberculosis; fe the latter case the condition is, ifiso facto, m the secondary stage. Fig, 1.--R%M mxtzonc of lung of machine mao of eight years* underground service. Tie vague shadows on be stm io the third and fourth intercostal spaces, measuring (root 2 to 5 bal TWs is the prsparmooasuotic stage. without disability; (2) primary--radiologseal evidence, with symptoms causing incom plete disability; (3) secondary--radiological evidence of pneumoconiosis, with clinical and 4, Chest expansion below 1 io. is considered evidence of dasninubed function but a surprisingly rare eves with advanced tadnlogfeal changes and occur* only with advanced emphysema or udectloo. $> Exercise tolerance is again diminished only is the presence of emphysema and/or mfeetko. The assessment of disability m these sub jects is often difficult, due to the unreliability of their symptoms and difficulty io carrying out even the simple tests required; the sig nificance of modem tests for pulmonary function would probably be equivocal. If is radiological fiedSpgs of active tuberculosis 194&-19SI and/or complete disability. respectively. 1955 Ootgxwa Wine figures, One stage is deemed to have developed into the next if chest pain, limitation of ex pansion, and dyspnea supervene, but this is an infrequent occurrence during the average working life unless tuberculous infection supervenes. Fig, 2--Right midtone of lung of machine mas of eight years' underground service. Smaller fine and paoetate shadows are well sees la tiit third sod fourth spaces and are quite discrete. The linear t&asfeisioi ol the fang parenchyma are still well seen. This is snteprim&ry pneumocoaiemy modes- ately advanced. The first comprehensive study of pntumocoaiosif on the Kalar Gold Fkld was jr*de by.QipUn and Burttou * (1947). Smee then, other workers have used their classifications and findings and modified them in the fight of subsequent studies until the foHowitig clinical* radiological, and pathological criteria have been adopted, which are in accord with the original Mysore Silicosis Rules. CMNXCJ& DIAGNOSIS There are usually no complaints or clinical findings in the ameprimary stage, which occurs in between and 90% ol those 1A --- PNsuuocomosis oh kolar gold meld Fig. 3.--Right nudzoae of lung of machine mao whh 24 Tears* underground service. Tins is the typical ptctare of the fully developed anteprimary arith fioe raotliinB, axtmfar shadows, and frames* obscuring the lung msrkicgs. possible that some men even exaggerate their symptoms id order to obtain enhanced com pensation. RADlOUKaCAL DIAGNOSIS Prefneumccotuatic Su$t.--K fee ttW* Ution first appears to the right midzone, with small ring-like shadows from 2 to 5 mm. in Fig, 4.--Heavily <fa$!~ladeB luug with focal emphysema: the dost aggregates are sees ia rtlatins to the Wood vessels. t*n upper lobe. diameter, at first vague in outline but later more discrete and smaller {Fig. 1). The underlying reticulation may give the appear ance ot haataess unless carefully examined. This stage does sot denote a sufficient degree of dust reaction to categorize as pneumo coniosis. but it is rather an alteration m the fine appearances of the lung through dust retention. The fiadmg of increased hilar shadowing and radiating lung markings is not consistent, though these are present oftener than not; it Is therefore not of value in arivtog at a diagnosis. Fiwa Nodulario* or MoWinp.--'The fine reticulation is followed by the appearance of very small, discrete; annular, and punctate shadows, 1 to 3 nun. in diameter and even smaller if examined with a lens; the annular shadows predombate. They begin in the right nadaone, later to (he left midzone, and Spread to peripheries, bases, and apices in that order, but the latter are affected only after many years* exposure (Figs. 2 and 3). In both the above stages, the linear marktogs of the lung parenchyma continue to be seen, together with the specific daoges, and this is regarded as fundamental when asses sing the degree of pneumoconiosis. Fig, S,*--Very heavy peribrooctoal and perivascslar dust aggregates a> a man who dice of Mar pneumonia after 25 years' underground service as a machine ean. Right lower Jobe, iv#| i n /t 'll] il V Discrete Mottling Affecting the Whole Lung Fields.--The shadows are more nu merous and slightly larger, but now only the Heaviest lung markings are seen, and tilt picture suggests a very fine, grotind-glass appearance. Fig. 6.--Grade 1 fibrosis; the fine retkulm frame work U aop^orixag the dw parrtvctes. SiVtaz irapreg' nation; x 1000. Diffuse Consolidated Shadows.--These shadows are indicative of active tuberculous infection which may obscure the underlying pneumoconiosis, When assessing these films, the following technique was strictly followed to gain uni formity. The projection was posttroftMerior, and the distance 72 in. The density of the film was such that the ribs and outhne of the vertebral column could just be seen through the heart shadow, but not the intervertebral spaces. The contrast approaches black and white a* for as possible. This is in accord with the suggestions pul forward at the Third International Conference on Pneumo coniosis, at Sydney, in 1950. By these means the normal Inog markings are standardized, and it is found impossible to detect the early fine spedfic changes (Stages 1 and 2) in a film that does sit* reach this standard. Between 1950and 1955 approximately 3O#0G films were examined and the above criteria were used. Fig. 7.--Grade- 2 fibrous; the reticufta is here more compact and coarser. Silver fanyregnatiotti x im Fig. 8,--Grade 2 fibrosis; the reticoUo is compacr. with early eol&gen formation. Silver impreg nation; X tOW. yATBOLOCICAL DIAGNOSIS Under tf?e Mysore Silicosis Rules, autopsy must be performed in ill cases where rela tives of the deceased have applied for pneu moconiosis compensation. The Labour Asso ciations lave advised the relatives to do this in almost every case of death in an under ground worker where there has been no recent chest x-ray. As a result, the material available for examination ovec the past 12 years has been considerable, and adequate criteria for histological diagnosis have been developed. Capfen and Burdon * (3947) have laid down the basic picture as follows: The characteristic lesion is the development and growth id size and number of tlucvoeU aggregate* wherein there is a minimal tissue cell -reaction. The bUtoVogj remains almost unchanged even when the condition has reached an advanced stage, until a tuberculous infection is super*impc*ed, when. PNEUMOCONIOSIS ON KOLAR GOLD FIELD cettotar, int(ration, fibrosis and casestioa become prominent features. The dust is deposited in the perivascular and peribronchial areas (Figs, 4 and 5) and in the nonfofective discs is not associated with any significant degree of fibrosis by ordinary staining methods, and one should not confuse the mass of dust-cell aggregates with the typical silicotic nodule. With the use of stfver staining (Cordon and Sweets,* 1936) a fine nticuUn framework supporting the dust particles at the aggregations is secs; in the absence of infection this does not pro gress to a significant degree. The assessment ofpneumoconiosis in relation to the stages of progression of the fibrotic process introduced by Ray and associates,* (1952) has been dust accumulations and is not associated with interstitial fibrosis, Siooe 1951 large tissue sections have been prepared In Professor Gough's laboratory in Cardiff from Kolai Gold Field lungs, and it lias been possible to see very deafly the distribution of the dust in the uncomplicated cases, as well as the focal emphysema de scribed above (Fig. 9). A comparison of the large tissue section with the x-ray film can be made and a dear relation defined. IXCWeNCE OP PNEUMOCOVtOSSS OK TliE KOLAS GOLD FIELD Figures have been very difficult to collect, because under the Mysore Silicosis Rules workera engaged prior to 1940 were exam- tw. IMS IMS MBS 1X1 Totd Toil) Min*** Ho, ' S.W i.tet vn lajnt Taii.R ir-lntidtnet of Pn***u>ee*?otis: 19(8-195} All Mines oo the Ketar Gold Field Ksrad Me. SM xsos MM PtrOene as.rx 9im 97JSE 9ims visa Aat>fen*t7 esoeooiod* S, PerOeat gi t*1 B ua M L97i n urn m SJM FrtBtrr Fatonseeded* Ho. Ter Cm\ U 0X0 u 0X6 u OSH *7 6Mt a ass BmaaAkej PXMUMOddl ' Ks. n a IS a f^Ccat 0X1 S3 tat 6X3 (C estt TWt yuamwxoaloWte So, 1-vCHat 12 SJU n Hi mm <7 mm B2 M1J used during the past year and has aided in getting a clearer picture. These authors describe five grades: Grade 1--loose rtficulin fibrils with no collagen Grade 2--compaet retleutin with of without some cottages Grade 3--somewhat cellular but nude up tnosdy <d collagen Grade 4--wholly composed of eollagen fibers and complexly acellular Grade 5--acellular, confluent, and (uMagenotu Pneumoconiosis on the Kotar Gold Field never progresses beyond Grade 2 (Figs. 6, 7, and 8), unless there is superadded infec tion, -when Grade 5 may be seen. An additional feature which has been noted is the ballooning out of alveofi on the periphery of Urge deposits, similar to the picture described by Gough and associates4 (1949) in the pneumoconiosis of South Wales coal miners as "focal emphysema," This, again, occurs only in cases with heavy joed only if they so wished. Large numbers of workers of the older age group did not avail themselves of this privilege. A tentative figure for the whole Field had been arrived at from a study of the men who received compensation betwece 1948 and 1951 (Table 1), Of 14,COO men, 2.8% re ceived compensation following clinical and radiologies! examination; from mine records, the 14,000 corresponded to two-thirds of the average yearly underground strength, but, at the sametime, one-third of the total under ground labor force had not been examined under the Rules, and the majority of these had over 25 years' service with presumably a significant-degree of dust retention.! Flow* ever, in 1953 Oorgaum Mine ceased opera tions after 70years, andall personnel were re quired to be examined, the total underground workers being 2243. It has been possible to I Of 423 sorb men examined prior to retiring in 1452. -44% had compensable pneotnoeonlosis. 77 FFRBHCH PNEUMOCONIOSIS ON KOLAR GOLD FJBLD arrive, therefore, at an ioddcoce of the eondition amoog agroup of workers who,up to the euste of the cktsurs of the mine, constituted nearly one-fifth of the underground labor force oo the Field and were m every way a representative group. This incidence was foimd to be 625 cases of all degrees of pneu moconiosis among 2243 workers (27&%), Of these, 384 cases <25.5%) were in the anteprimary stage; 32 cases (1.4%), m the primary stage, and 9 cases (04%), in the secondary stage. These figures arc probably more accurate than the totals so far given for the whole Koiar Field, because even up to the present time many of the underground labor force have not been examined under the Rules, mainly because they were tongservice max who suspected they might have pneumoconiosis and, as they were employed prior to 1940, were exempt from compulsory examination. EXPERIMENTAL STUDIES Caplaa and Burdoo1 (1947) found that the SiOr ce&ent of lungs varied from 0.7% in longs with very few dust-cell aggregates to 7% when definite pneumoconiosis was pres ent. The nominal fibrosis m relstba to the heavy dust-cell aggregates indicates that the dust is relatively innocuous, a conclusion that *s supported by the finding of a low disability rate (0.43% of 14,000 workers). It seems likely, therefore, that there is some factor present in the dust reducing the pathogen icity of the quafir component. This problem was studied by Ray and associates * (1952), who analysed the str-bornc dusts (Table 2) and conducted experiments on rats by intra tracheal injection of dust suspensions in order to assess its pathogenic effects. They found that, while the clear and the dark quartz, both of high solubility, produced sili cotic nodules in 120 days, the hornblende schist, mostly silicate and of low silica solu bility, did not produce any lesion greater than a Grade 1 fibrosis over a period of one year, and a similar result was obtained from the air-borne dusts of the different mines, ft will be seen from Table 2 that the total silica varies from 44% to 52% and AhOt from 10% to 11%. The presence of tite high aluminum oxide content may be of great significance, because these authors have pre viously shown that the presence of aluminous minerals is inhibitory to the silicosis-produc ing effects of quartz. They have concluded that os the Kolar Gold Field the aluminum oxide component is probably exerting an antidotal effect on the quartz. It would appear from .these studies that, if the quantity and percentage of hornblende schist in the air-borne dust is at any time reduced by change m rock formation or mining methods, a higher quart? content might result, leaving a greater proponion of silica which is not neutralized by the alumi num oxide, so that true si&osis may ensue. RELATIONS!*!? WITS TUBERCULOSIS The danger of pneumoconiosis on the Field is In the association with tuberculosis. It is for legal purposes designated the infec tive type of secondary siHcosis under the Mysore Silicosis Rules, The marked fibrotic reaction thatoccurs leads to interference with pulmonary function in those cases which do not succumb immediately to the tuberculous infection, and it b only in this type that the expectation of life is significantly shortened. like all the Inhabitants of Southeast Asia, the miners are very susceptible to tubercu losis. It has not been possible to obtain true figure? of metdazee, because many case? are as yet undiagnosed, and there is no process of official notification and treatment either on the Field or elsewhere in South India. However, the Incidence of radiologically ap parent tuberculosis among 2460 surface and underground workers in Oorgaum Mine in 1953 was 9 cases of secondary silicosis and 9 case? of puhnonar}> tuberculosis without pneumoconiosis--a total of 18 cases, or 7 per 1,000. \ It has been the impression over several years now that the presence of a significant degree of pneumoconiosis does increase the susceptibility to tuberculosis and may in crease the incidence of breakdown of the quiescent disease. There is no evidence as 79 pNEVuocomosis on xolar gold field to how this happens, and ft is difficult to see how the tuberculous infection could be in fluenced, as it) true silicosis, when the effect of silicon dioxide has already been modified in some way, possibly by the aluminum oxide of the mixed duat; on ttw othw baud, \K posable that the tuberculous infection en ables the silica to be released and so act as a fibrosiog agent, either alone or in conjunc tion with some specific factor developed in the course of the tuberculous infection. The suggestion put forward by Robson and associates* (1934) that injections other than tuberculosis may influence development of silkosis would not appear to be borne oat on the Kolar Gold Field, where the under ground workers have as incidence of 18 per 10CO of primary pneumococcal lobar pneu monia alone (Hrench, 1953) without the subsequent development of fibrosis. Robson and associates showed by animal experiments that exposure to the irritant action of gases from txptorives and sulfide-containing locks, combined with dust exposure, did produce silicotic kriofis, whereas dust alone did not. It is interesting that such cases do not occur on the Kolar Gold Field, owing to the differ ent methods of mining and types of rock. cal aspect of mine dust is beyond the scope of this paper, but it touches on the aluminum factor id the prevention of silicosis. Not until the indigenous peoples of India become less susceptible to tuberculosis will pneumoconiosis on the Kolar Field cease to be a financial burden to the authorities. The compensation received for all types of pneumoconiosis is considerable. The amount paid by the companies m 1952 was $82,311, and In 1953 it was $168,601; hence any methods that will reduce the dust hazard will pay off. The total number of cases com pensated was 251 in 1952 and 860 in 1953; this latter figure is high because of the closure of Oorgaum Mine m 1953. The Mysore Silicosis Rules were framed only to 1940 to cover all industrial processes giving rise to dust disease of the lung though it had already bees realized in 1934 that a radiologically apparent pneumoconiosis ex isted. The Rules were drafted from those which existed on the WStwatersrand in South Africa before it wa$ realised that dis ability was not always associated. By follow ing too closely the South African legislation, the Mysore Rules came to be silicosis rules, which implies that classical silicosis predomi COMMENT nates on the Field. This is not so, but never theless in the official courts the same stands. To describe pneumoconiosis on the Kolar Gold Field as a severe health problem would be overstating the case, ft is primarily a radiological condition but at any time might assume more serious proportions. Since it was described by Caplao and Burden* (1947), it has received increasing attention, and it must not be confused with the pneu moconioses that occur elsewhere is India, particularly the silicosis in the mica mines in Bihar, in the steel industry in Mysore, and in pottery and other works. Hie extent of pneumoconiosis in India ts only just feeing uncovered, and with the dual types of in dustry--mining or factory on a large scale and family mining and village crafts, it will SUM MAEv The type of pneumoconiosis occurring on the Kolar Gold Field is described, together with the clinical, radiological, and pathologi cal criteria for diagnosis. Experimental studies of Kolar Gold Field dusts by other workers have indicated that the relatively high aluminum oxide content of the air-bomc dust may account for the rela tive harmlessncss of the condition. The relation to tuberculous infection is stressed. It is only when the two conditions occur together that life expectant is short ened. be difficult to arrive at true estimates. Hie inference to be drawn from the work of Ray and associates 1 (1952) on the chemi Dr, A. R, RtddeJf, of the Department of In dustrial Hygiene, "Province of Ontario, and Dr. J< C Jeffrey, Chief Medical Officer, Kolar Gold Field, offered valuable criticisms in the preparation of 8! * ... FFRBNCtt Vhfa fsqper. penatission to publish was grilled by John Taylor and Sooj (India), l_td REFERENCES C Bay. S. Cj Kina, E^J.1 Httriion. C V, **4 Manswrty, C, F.; Studies oTifie Tissue Raetioa yffi-pf ao<j SiGca Dusts from the Kolsr Gold SGsea, Ti. ln*n. Msn. & Met*!). K't-Z Caqdan, A.r and Burdon, D, J.: Pneumocojiio *** *c fiir KoUr Go)d Field, in Proceedings of of Mrnittg Engineers and Institute of smd Metallurgy Coofrrffx* <** Si')kc*U, 'Vvnaxxcsosis, and DbM Suppression in Mines, ' y*. 55^7, \W. 3. Gordon, R, and Sweets, K, H, 5^* A SanpJe Method for tfce Silver /mpjejfoahoo of Retktfum, Ant J. Path. U:S4S, 1936. 4. Gough, )&ctes, W. R. L, and Weorwottb, /. .: Comparison of Radaotegtol and PaOwksita) Changes in CoaJ Workers' Pneumoconiosis, J. Fae. Kadi'oJogVsts 1:28, )W9. 5. Robson, W. D.; Irwin, D. A,, and King, E- J.: Experimental Silicosis; Quartz, Seriate and Irritating Gases, Canad, M. A. y tts237, 1534. 6. Ffreach, G. .: Ejaderniriogy of Inbar Pneumonia on the Kolas Gold Field, Proc. See Study Indust. Med. #il, 1953. tej-' ' 7 -1* ^Jlte 2)j/ m Cjreat Britain A. I. & MeUUGHLfN, HR. FiCJ*v U**m markable contributions of the Scottish physi cians of the 2800's on the connection between The story of dust diseases in Great Britain goes bade a long way. . L. Coliis, in his classical Milrqy Lectures of 1915, quoted Herbert Spencer as saying tliat the starting diseaseof the lungs and coal dust; he also tells how the incidence of anthracosis diminished with improved ventilation of the mines. The Scottish phytidaos decided that simple coal dust was comparatively harmless and that point of human progress was the "localisation stone dust was the really noxious factor. of industries." There was such a localization in prehistoric factories for the making of Hint implements at Grime's Graves, near Brandon in Suffolk, where the Hint knappers still use tools like the deer-horn picks of their prehis toric ancestors. In 1914, Colfss showed that these workers have a high mortality from silicosis. He said that It is probable that "the starting point of human progress'' was asso ciated with at least one form of pneumoconi osis. It has been long known that the dust of flint, which Is nearly pure SiO, is dangerous to health. Over 200 years ago, Thomas Ben son, of Newcastle under Lyme, was granted a patent for grinding dints by a wet method. At that time it was said that a man who ground the flintsdrycould not live longer than two years. Our greatest localization of industries took place during the Industrial Revolution, and this was really the starting point of our in tensive knowledge about the effects of dust on the lung. The first notable contribution was that of Pearson (1813), who, after many autopsies, decided that the black pigment in the bron chial nodes and the lungs was due to the in halation of small particles resulting from the burning of coal, wood, and other inflammable materials. The German pathologists, on the other hand, thought that the pigment came from inside the body. Meikkjohn (1951) has described the hitherto little-known and re Charles Turner Thackrah, a physician in Leeds, played a major part in the study of oc cupational diseases (induding the dust dis eases) in Great Britain. In Iris bode "The Effects of Arts,Trades, and Professions," the second edition of which was published in 1832, he crystallized the idea that the inhala tion of large quantities of dusts of any kind can damage the lungs but that some dusts are more harmful than others. His conclusions were based on first-hand observations of workers in hospitals, in their homes, and in the factories. Two other great Englishmen in the history of pneumoconiosis about the middle of the !9th century were T. B. Peacock and E. H. Greenhow. Peacock first established miners' disease as an entity and distinguished it dinjcally from pulmonary tuberculosis before little was known about bacteriology and noth ing about x-rays. Greenhow carried out the first large field investigations into tlte dusty industries of England and Wales, including the heavy-metal industries, the potteries, coal, copper, and lead mining, and even agriculture, In the Transactions of the Pathological So ciety of London (1860-1866) there are to be found excellent descriptions by both of these physicians of the disease, which was later to be called silicosis by Visconti, in 1870. They even found the dust of free silica in the lungs and examined it under polarized light. For a long time after this excellent work Recorded for pubKcatkm April 7, 19SS. H. M. Medical Inspector ol Factories. nothing much was done about the dust dis eases, but about the beginning of the 20th 83 McLaughlin ccdfury % new interest began to be fakes is In the last 50 years in Great Britain (as the problem not wily in England but also in elsewhere), there has been intensive research other parts of the world. Abofrt the same into all aspects of the dust diseases, such as time the tempo <A fife in general began to in crease, and there was an urge for increased speed ofproduction--an urge which has grad causation, pathology, incidence in various in dustries, and prevention. For the first 25 years or so, much of the impetus came from ually gathered momentum- With the replace H. M, Medical Inspectors of Factories, and ment of hand labor by the machine, dusty prominent in the study oi the chest diseases processes have become more dusty and meth were Collis, Middleton, and Merewether. It ods ofdust control have lagged behind output. might be said that they played almost a lone The result has been a remarkable increase of hand, with meager facilities for investigation. the incidence of the dust diseases. However, they were helped greatly by hospi A noteworthy contribution in 1892 was Arlidge's book on the occupational diseases, which was only the second to be published in England. tal physicians, general practitioners, radiolo gists, and pathologists, notably Hall, Robertshaw, Kettle, Gloyne, and Cooke. Duringthis period much attention was paid to rilkesis, In 1904, J. S. Haldane and his colleagues ascribed the high mortality among tin miners to the inhalation of rock dust A fa'ttle earlier, dust phthisis among slate workers was shown to be related to the dust of slate, particularly when it had a high quartz content. E. L. Collis (3915) pinpointed the dust of free silica as die main cause of most of the dust diseases. He also drew attention to the role that dust inhalation plays in determining the mortality from lung diseases experienced by the general population. Long ago he showed the influence of air pollution on the mortality from Jung diseases in general. Though Collis did this work 40 years ago, he \% always up-to-date. He bad, and still has, an uncanny knack of seeing to the heart of any problem. Just now in England there is controversy about chronic bronchitis and emphysema and whether they can be held to be caused by die inhalation of dust It is true that the incidence of chronic broachitis and emphysema is high among the general popula tion, and the possible causes are tegion. It * and it, with tuberculosis, was established as being the cause of disability and death in most of the industries where there is exposure to the dustoi free silica. Peri passu, regulations laying down dust-control measures were is sued by the Factory Department for most of the major industries. Notable contributions were GrfKs'a work,already mentioned.cm the role of free silica and Middleton's field in vestigation (with . L. MaeWm) into the. grinding industry in 1923. In the late '20*0 a series of brilliant observations by Cookeil Gfoyne, Burton Wood, Stuart McDonald, ana/ M. J. Stewart on the clinical, radiological^ and pathological features of a new disease] which Cooke named asbestoris, ted to field in-j vestigations by Merewethcr and Price (1930)i These firmly established that the dust of 3S| bestos was dangerous to health, asd it was\ the first time that the dust of combined silicas as opposed to free silica, was found to damageX the lungs. The condition, as Leggc points out, was first seen in 1906 by Murray at Charing Cross Hospital, but little or no notice of it difficult to decide (in Arlidge's words) how was taken at that time. much of the malady is "town-made" or '`trademade." But as Colli* showed years ago, an agent which irritates thelung parenchymacan An important landmark was the passing of the Workmen'? Compensation (Silicosis) Act of 1918, which came into force in 1919. also irritate the bronchial mucous membrane. For the first time compensation for disable At present there is one industrial pulmonary ment or death was given in respect of an in disease of which the diagnosis is made largely dustrial pubnonary disease. The Act pro on the presence of chronic brorwhitis and vided initial and periodical medical examina emphysema, and that is byssinosis. tion of all workers in the refractories industry DUST DISEASES IN GREAT BRITAIN and suspension from the industry oa a diag nosis of simple silicosis as well as silicosis with tuberculosis. The medical officers re sponsible for the examinations were the Tu berculosis Officers of the Local Authority ad ministering sanatorium benefit under the National Health Insurance Act The scheme was revised in 1925, and again in 1931, to provide for examinations by a medical board. This was the beginning of the whole-time Silicosis and Asbestosis Medical Board under its first (and only) Chkf Medical Officer, C. L. Sutherland. A dose association began between the Medical Inspectorate of Factories and the Silicosis and Asbestosis Medical Board, both groups working under the Home Office. In general, the Medical Inspectorate made the field investigations which established the risk of silicosis (or asbestosis) in an industry or process and which led to the establishment of the various compensation schemes. But the members of the Board (stationed at Sheffield, Manchester, Stoke on Trent, and Cardiff) also carried out field investigations into vari ousindustries, such as sandstone (Sutherland a&d Bryson, 1929), granite (Sutherland and Bryson, 1929), and potteries (Mefldejohn, 1949). But perhaps the most significant re sult of foe formation of the Board was that there was begun a systematic and valuable collection of case histories with x-ray films, together with occupational details and post mortem findings. Al first the Board was limited to a few in dustries, but gradually its scope has increased and more and more dusty industries have come under examination. Workers in the re fractories industry first came under a com pensation scheme in 1925, metal grinders in 1927, and sandstone workers in 1929, In 1928, the Various Industries Scheme included the processes of mining, quarrying, drilling, and blasting in silica roek. the crushing and grind ing of siliceous materials, and also isolated processes in steel foundries (not iron foun dries) and metal works, in potteries, and in tin mines. In 1934 the Various Industries Scheme was amended to include coa! miners with silicosis; is 1935 hematite ore miners were included, and in 1939 slate miners. Workers with asbestosis were first compen sated in 1931; compensation for byssinosis was introduced in 1941 and was dealt with by a specially constituted board. Pneumocoaicsis, as opposed ioclassUsl silicosis, in coal miners was brought under the compensa tion schemes in 1943 and in coal trimmers in 1946, The Various Industries Scheme was again amended in 1946 to include moldcrs of iron castings who used siliceous parting pow ders and also Masters of any type of metal eastings to free them from adherent sand, even if the blasting abrasive was nonsiliceous. The National Insurance (Industrial Injuries) Act was passed in 1946 and altered the whole basis of compensation in that it became the re sponsibility of the Government but with con tributions from employers and workers. Ber yllium "poisoning" became compensable in 1949. In 19S4 all foundry workers (iron, steel, and nooferrous) became entitled to com pensation under the Industrial Injuries Act. A fuller account of the development of com pensation in Great Britain has recently been written by Meiklejcha (1954). The Silicosis and Asbestosis Medical Board was trans ferred from the Home Office in 1946 to foe Ministry of National Insurance (later com bined with the Ministry of Pensions), The Board was divided into a series of Pneu moconiosis Panels, but they work in much the same way as the Board did, except that there is now no Chief Medical Officer. The various compensation schemes men tioned above reflect foe evolution of the study of the industrial lung diseases in Great Brit ain. There are comparable legal enactments and regulations designed to control the risks in each industry, but they are lew numerous to mention in detail. To "flash back'' a little, in 1936 Middleton, in his MUroy Lectures, reviewed the position of the dust diseases in Great Britain. He covered all the dusty trades, including coal mining, but at that time only cases of silicosis in coal miners were recognized as being eligi ble for compensation. Most of the miners, fiS MctAUGmjX such a$ hardheaders, drifters, or rippers, had been exposed to stone dost, but Middleton also showed that there was a high incidence of a fang disease among coal miner^articuiariy in South Wake, which was not classical sili cosis. Much of his evidence was drawn from the findings of the Silicosis and Asbestosis . Medical Board. Following his paper, there began a series of intensive investigations by the Medical Research Council into the health risks of cord mining, which covered all as pects, such as clinical, radiographic, and enviromoental (Medkal Research Council Spe cial Reports 3 [1943], II 13943], and HI (2945J). The important fact emerging from this work was that coal dust by itself could caaw pneumoconiosis, and this was followed, as previously mentioned, by the esetenriott of compensation to coal miners and coal trim mers. 3n 3945, the Pneumoconiosis Research Unit of the Medical Research Council was set up in Cardiff, and an impressive body of work has emerged on various aspects of coalminers' pneumocomosu. This work is weft known, and I propose, therefore, to limit my remain ing observations mainly to the dost diseases resuming from work *n places which come under the Factories Acts, with only inciden tal references to coal mining. 3. Stone quarrying, crushing, and dressing. This group includes workers with sandstone, millstone, gritstone, slate, granite, and other igneous rocks. The risk varies with the amount of free silica in the rock and, of course, with the protective measures adopted. Recently some limestone qusrrymen have contracted silicosis, but the limestone con tained a fairly high proportion o( free lka,* In this group could be included rock tunnel* ers, in whom the onset of silicosis may be very rapid. As regards slate workers, a bil liard-table maker lias recently received com pensation for silicosis. gyms n?OM sitcoss nmttai Gfigcfss {93CH951 -a liiliiili! sfrs2!l!$32itills SILICOSIS Silicosis has been found to be a cause of disability jn the following broad groups of in dustries *s> well as in coal mining and other formsofmining, such as tin, hematite,copper, barites, and fire day. 1. Refractories industry. This group in cludes the making of silica bricks, furnace dismantling and rebuilding, and retort setting and repairing. 2. Pottery industry. Workers in this group have been engaged in the manufacture of both earthenware and china with their various subdivisions and as flint millers and polishers. The substitution of ground Sintbyalumina for the placing of biscuit ware has resulted m a diminution of deaths from silicosis among workers m that process, 66 * Fig. 1.--Chart sitowing- diminishing numbers of deaths among saeiaj grinders during the wriod 3930-1951, inclusive. 4. Metal grinding. The silicosis risk in the grinding of metals has greatly diminished, owing to the replacement of the sandstone grinding wheels with artificial ones composed of Carborundum, alumina, or emery. Apart from the lower "toxicity'' of the dusts from these substances, the wheels are much harder than sandstone, and Jess dust is created. But the grinders of castings (iron, Mtri, and nonferrous) arc still exposed to a silicosis risk on account of the presence of burned-on sand on the castings. The diminishing number ol deaths among grinders is shown in the chart (%.!)> Doig, A, T-: Unpublished date DUST DISEASES IN GREAT BRITAIN 5. Sandblasting. This job, as Merewether (1936) showed, had a high silicosis risk. The position has altered materially after sand be gan tobe replaced by other nonsjliceoos abra sives, such as steel shot, and since the use of sand as an abrasive was prohibited in 1949 by the Blasting of Castings (and other Articles) Regulations. The process of wet sandblasting of ships' hulls does not come under the Regu lations (because legally a ship is not an arti cle), but it is thought that there is also a risk of silicosis in the job. Sandblasting is still used in the open air on works oi engineering construction, . g., in order to prepare large metai surfaces for the application of paint. 6. Manufacture of abrasive soap. Middleton showed In 1936 that the manufacture of abrasive soaps tarried with it a risk of acute or subacute silicosis, accompanied by tubercu losis, There was a disastrous experience at one factory m London between 1921 and 1928, when there were 13 deaths among 81 workers. Thisexperience led to rigorous dust control in the processes, but between 1941 and 1952 there were nine deaths from silicosis among this type of worker. It k not possible feet that tbedustfrom the pneumatichammer feootcoBtroUed. Tbe imunpathological lesioo was cUfiskal riUcoals, with or without tuber culosis. Among iron fettkrs, tbe risk was not so great as among steri fettiers, and the main pathological lesion found was mixed dust pneumoconiosis, though classical silicosis did occur. Steel moldcrs were lessaffected bydis ease and disability than Iron moldcrs, though statistically the incidence of x-ray abnormal ities was greater among steel workers. More deaths occurred among ironmoldecs, and this fact appeared to be related to the use of siliceousparting powders.Tbe use ofsiliceous parting powders has sow been prohibited by tbe Foundries (Farting Materials) Regula tions, 1950; Silicosis still occurs among shot blasters of both iron and steel castings, but tbe risk is <trolled by ventilation and per sonal protective devices, and the numbers of cases and deaths, in contrast with the experi ence among steel fettlcrs, are not increasing. Other categories of iron and steel foundry workers are subject to much less risk than the above groups of workers, blow and strin to state the incidence of disease anti disability, gent regulations (Iron and Steel Foundry because these is a rapid turnover ot labor Regulations) were issued m 1953. They re (mostly young women) in the job. Silica quire strict dust control in the dusty proc Sour is stiU being used as an abrasive, though esses. efforts are bring made to find a less harmful substitute which will be acceptable to the manufacturers and the users. There were no new cases of silicosis in this trade in 1953. 7. Foundry industry. The iron and steel foundry industiy has been investigated in great detail during the past 10 years or so, and the results were published in 1950 is book form by McLaughlin txvd others ("Industrial Lung Diseases of Iron and Steel Foundry Workers"). Pathological studies oi 64 cases, as well as clinical and x-ray examinations of some 3000 workers, allowed that there was a varying risk of silicosis and mixed dust pneu moconiosis (to which reference is made be low) in tiie various categories of foundry workers. The question of pneumoconiosis among nojiferrous foundry workers is now being ex amined indetail. Isolated cases of silicosis and mixed dust pneumoconiosis have occurred among bothcastersanddressers of nonftrrous metals, but an extensive survey has not yet been carried out. Harding and McLaughlin f have described the pathological, clinical, ra diological, and environmental details of six fatal cases. 4 Table l shows the number of new cases of pneumoconiosis (i. e.,silicosisandmixed dust pneumoconiosis) in foundry workers diag nosed by the Pneumoconiosis Panels in 1953. These figures can be regarded as an under statement of.the real position. More than half Steel tetters (diessers or castings clean t Harding,'5}< E,, and McLaughlin, A. I, G.: ers) had a severe risk, largely owing to the To be published. 87 r UcJMGHLW Tabu? \.--No Cases of Fnevmeceniosis--X9& Foaodries GB0CfoB Il9B BOittf................................ ............. Iroa foaMiT totaakoo*...... ,............................. Sm) (BOkUnc..,^........ ............................... 6tJ dmatn*................................... HeeJuwoj ftnatfl&f................................................... Walnut* Ai teSMs* Q& Altaic hapa) ................................................................ ... Gnnl IoobSt? *etk............................. ............ T*UJ........... ................................... TcUl f? fi 1 < 46 s T9 S* J*2 * T*afy-a*v*D of tteac workm fa*4 alse tats uictad to Mj tfuit for ported*. of the cases in iron molders came from one area where there had been an x-ray survey of three foundries. If more iron foundries had been similarly surveyed, more cases would have been bund. Incertain steel foundries the dressers (choppers or castings cleaners) are x-rayed each year, but a complete picture of the true position will not be obtained until all workers undergo periodical medical examina tion. This statement also applies to other dusty industries. In Table 2 detailsare given of fatal cases of sttkoris and asbestosss investigated fully by die Medical Inspectorateof Factories between 1930 and 3953. Theaverage ages at death and .the length of employment ht the dusty indus tries are also given. It is seen that as regards silicosis the manu facture of scouring powders and sandblasting were the most dangerous industries, with the lowest average age at death and the shortest average period of employment. Another in teresting point is tlt tuberculosis occurred in about half of the cases of silicosis, whereas it was found in only about two-fifths of the cases of asbestosis. The average age at death and the length of exposure In the cases of asbestosis were much lower than in the silicotic group as a whole but more on the level of sandblasters and makers of scouring powders^ f The connection between asbestosis and kancer of the lung is becoming dearer, and m rose series of 300autopsies on asbestosis cases there were 25 cases of cancer of the lung.Wyers {1949) has pointed out that the x-ray Tabu 2---Fatal Cases of SiHeosis a*4 Asbsstosit by Foster? Department, l95C-19$i S&mfe Sutlers SBSmvU ............................. ,.......... ............ EQMeata >** labmuMSe....................... SroftiUn* SQfcotu .................... ................................... . 6SM*li <4 tvtereatocU................ Grt#3tag at UetsJs ................................................. .. Siltcoiu wlfo OWmi}o"U...................... fiaitSbfoaUar fiOkoKa............................... ......................... BSteMU wft tobtrealuBta........................ IfosafMtQn f taDutBf pandttt AScMa............. ........................................... gUfceiU vltfi CutaraUoalt................... KltfBfiUdOUl ............. ............................... ............ EBcobi w)ii tvtamdoU................... .. totsi etiieosSa ...................................,,.......... . UMoU lotareufe***.......... ............. Astawsts ............ ................... .. AAtaBtMb Wjtfc tUbereofosM......................... U Lcttta, Ko. A<cmt A| il DeaUs. fr. orttlea IBjssienwAt Xcw/rat. BboMk, Jr. *. 4tA J gto SO UT ess tf?.o 9J3 |1 fl ST* es.o SO ftA mi *S* $6* * BO US tiO *6.0 IT SO US <05 *10 us IS SB *ro J<i vtss/' US so 0* it* DVST DISEASES IN GREAT BRITAIN appearances of asbestos*s are undergoing some change m that nodular as opposed to gTOuad-giass shadows are beginning to ap pear. He thinks it probsbkthat this is because of the lessened exposure to dust over a longer period, owing to the rigorous application of exhaust-ventilation to the dusty processes and the use of personal protective devices. Cases of asbestos*s> however, are cow appearing in workers who do asbestos lagging o! pipes and boilers. Is this process, particularly if as bestos is bring sprayed, it is difficult to apply adequate protectivemeasures, moreespecially because the workers are usually peripatetic. PSLESENT POSITION How many cases of pneumoconiosis (sili cosis, asbestosis, coal miners'pneumoconiosis. In all industries there were 8789 deaths from occupational fibrosis of the lung in the 12-year period, and it will be seen that the total yearly figures are going up. Over the same period there were6907deaths from nonoccupational fibrosis of the lungs. About twothirds of tlie total number of deaths in the occupational group occurred in coal miners, who form the largest group (about 700,000) exposed to dust inhalation. The figures rose steeply from 232 in 1940 to 937 in 5951 (in 1952 the figure dropped slightly, to 912). It may well be that part of the increase is due to more accurate diagnosis, or at least to greater interest in the pneumoconiosis problem, among coal miners. In Figure 2 is shown a comparison, based on the crude figures of Table 3, between the coal miners and factory Tasls 3,--Death/ from Ail Tyftt of PneamoemUsis in England end Wale/, 394C-19SI Xa&wtrf awe IMl I** 1M 2M IW 1M 1M? IMS IMS M4C JB51 PtitUrfcB................... SOB ...... ..................... ................... watHTTeiun*# nan r* Orlodiar 9i mt*u, tt*............ .............................. 4]*EUHcrrwren & BetTMKAM............................................................ ...... ............................... UT7#SS0UU8ar f* 7 U2<t82TSS?0U M7 Owu nuBia* ............................................................... aa)fniuinnrn<BWMe Mcs Otter nlsior................................ STS tltvm ....................................... .............................. II MU SUUUUISMUU Cotton CteMMCft).,.................................................................. 8 V i 16 9 4 8 7 S W C5 ijHsui........................................................................ <b*4ss 4 ***** ym 14U 8.1W Roaocnaptaoctl.................... wnMiistSMnSHMn i&t etc.) occur in Great Britain ? It should be mentioned that at the present time it is im possible to give accurate figures of the popu lations at risk in the various trades and proc esses. Both the Registrar-General and the Ministiy of Labour classify occupations in groups too broad to give specific figures of the populations in the dusty industries, and those in the possession of employers' asso ciations and trades unions are not complete. It may be possible in several years' time to give more accurate information. All that can be done now is to state the numbers of deaths reported to the Registrar-General and to give the figures for one year of the new cases diag nosed by the Pneumoconiosis Panels, The deaths from all forms of pneumoconi osis between 1940 and 1951, inclusive, in England and Wales arc given in Table 3. workers. In the factory processes, the yearly number of deaths was going down until 1943, but there has been a slight rise in the later years. In both groups, it should be emphasized that the deaths in each year are related to conditions which obtained in mines and fac tories some years previously, possibly 10 to 20 years or even longer. New Coses in Factory Occupations.--The following Table A gives the numbers of new cases of pneumoconiosis diagnosed by the Pneumoconiosis Panels in 1953. These fig ures have been kindly supplied by the Minis try of Pensions and National Insurance, but it should be coted that they differ slightly as regards the numbers in each occupation from the figures origittally supplied. The Ministry usually classifies the cases as falling into the 69 MtLAVGHUtf tesui nmmtms K!g. 2^--Oiart showing trends of deaths fjtfro 6hrovis of the hangs arson# ecaJ miners and tactory workers during the period 1940-1951, indusivt. category of the last Jobs done by the workers, whereas Dr. G. O. Williams, of the Factory Department,has reclassified some of the cases on the basis of all occupations done by each worker in order to determine the most likely cause of the pneumoconiosis. There wen &6 cases of ptieumoeoabsls diagnosed, and this figure includes 54 cases of byssinosis. The cases with an uncomplicated occupational history numbered 665, and in the remainder there was exposure Cor varying pe riods to other dusts, mainly coal dust. Addi tional exposure to coal dust occurred mainly m those industries situated in coal-mining areas, such as refractories, stone (sandstone and granite), pottery, slate, and foundry in dustries. The pottery industry contributed the greatest cumber oi cases (353,mainly sili cosis), and the foundry industry came next with 190cases. There are roughly 25,000 pot tery and about 220,000 foundry workers <iron, steel,and nooferroy$); soitIsprofeaWc that the pottery industry has a higher pneu moconiosis risk than foundries. Such general statements are not of much value, because the risk varies from process to process within the same industry. The substitution of ground Hint by calcined alumina has reduced the sili cosis risk among placers of biscuit ware in potteries, whereas the fettlingof steel castings is still a dangerous job. Nett> Cents in Minin#.--Table 5 gives the numbers of new cases of pneumoconiosis oc curring in all mining operations in 1953- The&e figures show deafly fre tremendous problem whichfaces the coal-mining industry. There is no space to give m detail the varying degrees of severity of pneumoconiosis found in the 4048 cases, but the figures are given in the 'Digest of Pneumoconiosis Statistics Table Cws tj Fnevmofe*wis--19S3 Factory Occupations la&irtTS 0) fletrectort** ................................................ O) stem witm <ftdiicQ, 0} *oit7 -.................. ................................ (*> ffiete worker* (^ns/ryUi* *M9 p);tda*>.. ) Poaaffrte* ...................... .......... .................... (fl) M4*l rrtodUu <oU*r tfeia foo&4rM*)...... <?> SAaesuitfii*...................................... . <a> soot wmou#................ ............................... . W Pursue tfWanatlteff, He............................. (Vfy BeSto auaac............. ......................... ................. til) w&eeJ taeftufftWuH......................... 0i) AM&atnt ......... .................. ................ <U> k\**&*x **a >o*e*n.................................. <1> Grephfte *Bd ofaciroOes............... (ay ysa uBotuu......................... ........ Off) Cettoa (BfM&otfs)..,.............................. . 07) Cki*I trtnmteB............................................... 0> ............................. ......................................... ...... ..... ............... .......... NoOtBer Post ETBoare 16 u s&t as iM S t t IT 4 s H 1 w 10 u Outer pnt Exposure Coal JO s # t i * ? i Olbrx i I* ,,a > ,, 6i .. .. ),,i K6 a *rt8? 36 66 ua KI 3 1 0 s a 8 8 .. J t* 30 U 8W 90 DUST DISEASES IN GREAT BRITAIN ?AU i.--Nm Cans of P*fum4coni4sU--I9$3 Wining * iada*!r >t Mo, Wi OMla&dai........................................................ ue <2> TU a&dBt........... t (9) Strife* ............................................... 1 (4) - day ttJaia# ............. ...............,............ { Otlr aU/ abtef............................................ (A) Btattlw jafeta*................... t 4 (?) 1*6 qSoUt*....... .......................................... t <8} TeoseUof ........... 8 Total.,TM,,.................................. ** Mo e*m Is am, ofl (*!*, or tutus* iraastoac sdalfifi Foart*ts flio eiy bluer* *** Uto exposed lo eoJ dUBt. (or 1953," issued by the Ministry of Fuel and Power (1954), It can be said, however, that more than 50% of the cases had only slight disability, and only about 3% were totally disabled. The number of cases in hematite mining Is diminishing, but the small numbers found in tunneling are usually instances of rapid and severe silkoris. DUSTS OTHER THAN SILICA, ASBESTOS, AND COAL About the middle 1930's the Factory De partment began to turn its attention to other dusts. Middleton, is his 1936 review, referred to dusts, such as tripoli, rilHmanite, ideselguhr, talc, china day, and fullers' earth. Ia the same year Doig and McLaughlin pub lished a paper on the x-ray appearances of the lungs of electric-arc welders. From this has arisen a world-wide study of the inert and radiopaque dusts, and notable American contributors have been Sander, Enter, Pen dergrass, Vorwald, and Hamlin. Perhaps the most interesting outcome of this study has been the alteration of the approach to the interpretation of x-ray films of the chest, because the x-ray features of siderosb, hali tosis, and stannosis, in the absence of occu pational histories and clinical examinations, can be mistaken for fibrotie changes in the hangs, In fact, an alarming x-ray picture is often found in a worker who has littk or no disability. The study of siderosis was helped by the excellent work of Stewart and Faulds (1934) and later Craw (1937) on the hema tite miners, in which group the lesion was found to be riderosilicosis, often accompanied by tuberculosis. Craw's later work (1947) is eliminating tuberculosis from the hematite mines and is improved dust control methods is of major importance. Other occupations and dusts which have been studied include those of boiler scalers, graphite workers, grain dockers, and workers exposed to beryllium and its oxides, to the dust of leather mixed with other dusts, and to bagasse. Attention has also been given to exposures to the dusts of aluminum, man ganese, and vanadium and to asthma occur ring in workers exposed to the double salts of platinum and also to various wood dusts, such as western red cedar. Pathology.--A great deal of work has been done on the pathology (gross, histological, and experimental) of coal miners' lungs by Gough, Harding, King, Heppleston, Wright, Gtoyne, ftagelschmidt, and others. I might, however, state some conclusions about pa thology which Harding and I (with our late colleague, S. Foodhouse Gtoyne) have ar rived at after studying the lungs of workers in many diverse industries. Until about JO yeafs ago, the pathology of the dust diseases was dominated by the class ical silicotic nodule (Fig. 3). In the same way, before a diagnosis could be made, the patient had to have x-ray uoduladon, or the classical "snowstorm" effect. Classical sili cosis usually occurs after the worker has been exposed to dust containing a high proportion of free silica. It is becoming increasingly clear, in our opinion, that even small propor tions of free silica in a dust can cause a fibro sis which is composed of nodules not of the classical type (Fig. 4). The arrangement of the fibers is linear and radial, and the outline of the whole nodule Is stellate. It looks like a black star, .narttmg, Uloyne, and 1 have applied the term mixed dost pneumoconiosis, or mixed durffibrosis, to this nodufc. It has been found ifljfoundry workers, especially m cleaners of iron castings, in persons exposed to the dust of graphite containing about 10% free silica, and in boiler scalers who are ex- 91 MeLAUGHUS Fig. 3.--Clascal eiiicotic sedate frost limg of gold mint* (30 rears old)) Hematoxylin aod eostsj X24. mixed dust pneumoconiosis nodule Indeed* there are also nodules which show a transi tion stage between the mixed dust nodule and the classical one {Fig. S). ft should be men tioned that the x-ray appearances of the lungs of a worker with mixed dust pneumoconiosis differ littk, if at all, from those oi one with sycosis, sod the disease is just as disabling and as fatal. Boiler Seders' Pneumoconiosis.--Experi ence of pulmonary diseases in ships' boiler caters illustrates wdl the etiology ol mixed dust pneumoconiosis. These men are exposed to a mixed dust which varies according to the type of fuel used to heat die boilers and also accotdmg to the source oi the water used posed tv a mixed dust with a low proportion of SiO*. The cos) nodule of coal miners' pneumoconiosis has much the same appear ance as our mixed dust pneumoconiosis nodule. Coal contains varying proportions of free silica. In any case, the common de nominator in those cases and occupations In which this type of nodule is found appears to be the presence of a small proportion of free silica in the dust. Where there is a high pro portion, as stated above, the classical silicotic nodule is found. But in the same case, there may be both the classical nodule and the Fig. 4,--Mixed dust pueumoccnkms coduk from a Wed tenter's lung; HeamoKyhn and ecssa; X 24. Fig. 5,--Transition nodule* frees inured dust pseucoocotaosis nodule to riticotic noduk is as iron dresser's lung; HestAtoxyUn and eosto; X 24. in them. It contains carbonates, silicates, iron, and carbon. There is usually under 5% oi free silica, but there is often a high pro portion ol iron and its oxides. Flue dust contains more iron than docs the scale on the water tubes, sometimes as much as 48%. In the first case of boiler scalers' pneumo coniosis the worker had been scaling boilers for over 40 years (Harding, Tod, and McLaughlin, 1944). Ic 1938 an x*ray film oi his dies! showed copulation the upper and outer lung fields, and in the lower zones reticulation (or mkronodulatton). At that time we made a tentative diagnosis of sili cosis in the upper rones, with siderosis in the lower rones. Seven years later the patient 92 DUST DISEASES IN GREAT BRITAIN died of cancer of the lung, and histological able to study the histological appearances of examination of the lungs showed (apart from a proved c?*- of tak pneumoconiosis (Mc the cancer) the presence of classical silicotic Laughlin, Rogers, and Dunham, 1949), nodules in the upper and outer rones, and in A man, 51 years of age, had worked for the fewer zones (where there was x-ray 37 years in a rubber-tire factory, where he reticulation) there were mainly deposits of h*d been exposed to a fairly high concentra carbon and iron dust in the lungs, with no tion of tak dust. Moderately advanced pneu fibrosis. In all other parts of the lung there moconiosis of both lungs was found at au were nodules of mixed dust pneumoconiosis. topsy (fu addition to incompetence of the Up to tiie present time we have had autopsies aortic valve). Throughout the lung substance on nine boiler scalers, and all showed this were scattered small gray nodules, more type of fibrosis. Only one scaler had classical numerous in the lower lobes. In some areas silicotic nodules in addition. But five of them the nodules had coalesced to form small also died of cancer of the lung, and this may masses. The fibers appeared to be arranged well have been partly caused by cardnogeclc concentrically around small vessels, giving substances present in the soot. the impression of whorling, but not like the The change from coal to oil as a fuel for ships' boilers has brought with it another problem. The dust from oil-fired boilers causes symptoms of bronchospasm or asthma in a high proportion of cases, and it is likely that this is due to the presence of vanadium in the oil soot. Williams (1952) has published an interesting series of cases illustrating this, point. My colleagues and I are at present examining (with clinical, radiographic, and environmental details) the boiler scalers (tome 300 of them) in the port of South ampton, where the boilers of ocean-going and large passenger liners are cleaned. The inves appearance of silicosis. There were, in addi tion, many "curious" or talc bodies, resem bling, but easily distinguishable from, asbes tos bodies. Much dust, which proved to be tak, appeared in the sections, and it was thought at the time that die particles were all fibers. More recent work on the lung by Nagelschmkk t has shown that the bulk of the dust is in the form of plates with only a few fibers. At least three other autopsies on cases of talc pneumoconiosis (all from rubber works) have been made, and they show similar fea tures to the first published case. Small sur tigation has not been completed, but up to the veys have bees made on workers exposed to present we have not found as much lung talc dust in various industries, but larger damage as was shown in a previous inquiry ones have been planned to take place shortly. in the port of Hull, where the boilers of It is clear that tak dust, though fibrogenic, is fishing trawlers are mainly scaled. So far we have found three cases of compensable pneumoconiosis among 50 workers and one not so active as asbestos in damaging the lungs. Leather Dressers' Pnevmcconicsis.--Co case of cancer of the lung, together with a operation between the directors of chest clin proportion of cases with lower degrees of ics, the mass radiography units, and the pneumoconiosis and disability. Medical Inspectorate of Factories has been Talc Pneutnoconicsis.--A great deal of work on talc pneumoconiosis has been done in the United States and Canada (Drcessen, 1933; Dreessen and Dalla Valle, 1935; Riddell, 1940; Siegal, Smith, and Greenburg, 1943, etc.). Merewether (1933-1934), in England, studied the x-ray and clinical instrumental in bringing to light hitherto unsuspected causes of pneumoconiosis. Since the mass radiography campaign was begun in 194S for the early detection of cases of pulmonary tuberculosis, some 13,000,000 per sons have undergone examination. Many factory populations have been surveyed, and features of rubber workers exposed to tak t NageSschreJdt, G,: Personal eomcnuroeatioe to dust. But it was not until 1949 that we were the author. 9$ UclAVCHUN included among them have bees factories mental details of five noofatai cases, one of where there i& a dust risk. The wtr&ers at whom is now very iU. The other four cases one leather factory were examined by Dr. are either recovering, or their condition is Hugh Ramsay, of the Wanstead Mass Radi Stationary. It is also renarkable that five out ography Unit, He drew trot attention to the of six affected workers were chemists en fact that in one department a high proportion gaged in the development of the beryllium of the workers showed abnormal x-ray lamp powders. At the factory where the fatal changes, whereas in< other departments, case of beryllium granulomatosis occurred, where there was no dust, no abnormalities 150 of the other workers were examined were seen. In the department with the high clinically and radiographically and no more proportion ol x-ray abnormalities, skins cases were found, though there had been con loaded with china clay and calcium carbonate siderable exposure to the dust of the lamp are dressed on rapidly revolving felt wheels powders in the early days. It is undeniable covered with a layer of fine Carborundum that beryllium oxide is toxic, but examina powder. The job is very dusty, though it is tion of the histology of the lungs of the one done under exhaust ventilation. The dust Is fetal case has Jed me to hold the unorthodox composed of much fine leather dust, with view that beryllium was not the sole cause of smaller proportions of china clay (kaolin), the condition. There were two types of le calcium carbonate, and Carborundum. It was sion : one of a granuksswAous type, sa which found that the dust contained about 5% of there were giant and epithelioid cells, and die free silica. The x-ray films showed all stages other in which were many fibretic nodules of abnormality, varying from early reticula indistinguishable from silicosis. Under polar tion (micronodulation) through oodulation ized light many doubly retractile particles to massive shadows. In a few cases there was were seen in the nodules, and an eminent clinical evidence of disability. One man with erystaliographer stated dial these were cristo- an x-ray film showing massive shadows had bahte, one of the most active forms of free died from "asthma and pneumonia0 a year silica. This is not surprising, because one of before the investigation, began, and these was the ingredients of the lamp powder is silica no autopsy. In spite of the fact that up to gel (25%), which in the preparation of the the present time no pathological evidence has powder is heated up to about 1100 C. Tbe been available, it is likely that the condition changed methods of preparing the lamp pow will fall into die group of the mixed dust der have eliminated both the betyIlium oxide pneumoconioses. The dust of china day, and the free silica, so that the risks both of whkh for years has been thought to be com beryllium granulomatosis and of silicosis have paratively harmless, is becoming more and also been eliminated. more suspect. Even apart from china day, the presence of a small proportion of free silica is prima fade evidence that the dressing of such skins is a hazardous occupation. "Pneuworoirioris" from VegeiebU Dusts--Apart from cotton, not a great deal of work has been done on the vegetable dusts. The illnesses noted among cotton workers Beryllium Pneumonitis e,nd Gruxulotnoto- include mill fever, a transitory illness which sts.'--It is remarkable that British experience affects nearly all new workers in cotton, flax, of beryllium pneumonitis and granulomatosis and Hemp mills and also in malt houses; is not as extensive as that in the United "Monday fever" (or feeling); weavers' States, though many workers have been ex cough, and byssinosis. posed to the duet of fluorescent lamp powders containing beryllium oxide and also the dust and fumes from the alloys. Only one death Byssinosis develops after about 20 years as a natural progression from "Monday fever" and in its final stage has the characteristics has occurred, and the Factory Department of chronic bronchitis and emphysema. As has collected clinical, x-ray, and environ- Schilling (1954) says, though it was de- 94 PVST DISEASES IN GREAT BRITAIN scribed by Greenhow nearly 200 years ago, . Thirty of these men had pulmonary tubercu its etiology is still obscure. It presents aa odd losis, but 12 others had x-ray changes sug but characteristic history oi chest rightness gestive of the presence of pneumoconiosis. and breathlessness on Mondays, which grad, Fourteen had normal x-ray films. Analysis ually extends to other working days as the of the dusts from various grains showed disease progresses, "la its ktter stages these small percentages of free silica; oat dost, for symptoms are very distressing, but usually remain worse on Monday than on any other day. It causes no specific x-ray changes in the lung fields." In the main, the workers in the cotton card and blowing rooms suffer most from the disease. Strippers and grind ers who clean the carding engines are especi ally affected. As mentioned previously, work ers with byssioosis are compensated under a special scheme. Bagassosis.--Only one factory in the coun try handles bagasse (or sugar cane without rise sugar), and bagassoris has occurred instance, had 5%. No autopsies have been carried out, but it seems that a case has been made out for an extended investigation of larger groups of grain dockers. Graphite Ptuumoctmiosis.--It has been found by some observers in England (Dunner, 2945, 2948, and 1949 ; Gloyne, Marshall, and Hoyle, 1949, and Harding and Oliver, 3949) tliat workers exposed to the dust of natural graphite develop radiographic changes In the lungs and disability. The range of x-ray abnormalities closely resembles that seen in coal miners. Pathological and experi mainly in those workers who were grinding mental studies (Gloyne and others, 1949, bagasse io a dry state. The condition is an Harding and Oliver, 1949) show that the acute brottehioliris, with high -temperature, condition falls into the group of the mixed severe dyspnea, and x-ray picture of the lungs dust fibroses, the fibrotic nodules haring a showing generalised miliary shadows. Fif linear aod radial pattern as opposed to the teen cases ol thus acute disease have come to wboried fibrosis of the classical silicotic the notice of the Factory Department; some nodule. Natural graphite contains small per of these have been described by Castleden centages (of the order of of feet and Hamilton-Paterson (2942), GiHison and silica. There is as yet no evidence that pure Taylor (1942), and Hunter and Perry (2946). The last case occurred in 1948. Since we got the firm to grind the bagasse under water, there have been no further cases. Farmers Lung.---Farmers', or threshers', lung was first described by Campbell (1932), aod after that Fawdtt (1936 and 3938) did a great deal of work on the condition. It has features similar to bagassosit, but, since it occurs mainly among workers who have been handling moldy hay during a wet summer, it is regarded as being caused by a fungus. Fawcitt was firmly of this opinion. Single cases of the condition are described from time to time by physicians in the agricultural districts. Pneumoconiosis in Grew Doe&m.--Din ner, Herrnoo, and Bagnall described in 1946 the clinical features and abnormal x-ray ap pearances in a group of 55 grain dockers. graphite will produce a similar condition. Manganese Pneumonitis,--A few cases of manganese poisoning affecting the nervous system occurred ia the middle 1930's in workers grinding manganese dioxide for use in lamp batteries. In 1946, Lloyd Davies re ported a high incidence ol pneumonia in a group of workers exposed to manganese di oxide dust in the manufacture of potassium permanganate. Animal experiments by Upyd Davies and Harding (1949) confirmed that manganese dioxide irritated the lung tissue and caused intense infiltration of the alveolar walls and alveoli. Later granulomatous changes developed in some instances. These results are in line with those described by workers in other countries. Vanadium Pneumonitis.--Wyers (2946) recorded his observations on workers exposed to vanadium peotoxide dust, and his results 95 *i tf .`i si ii McLaughlin are similar to those described by Sjoberg which make a dusty process more dusty and (1949) in Sweden. The effects are**'combi cause a lag in dust-control methods. nation of systemic poisoning and irritation * 3. Compensation for industrial pulmonary of the pulmonary tissue, leading in some disease began soon after 1918, and gradually cases to broachospasm and pneumonia. most of the processes and industries which Doig and Williams (1952) Have described damage the Jungs are being brought under the marked bronebospasm occurring in the provisions of the various Acts of Parlia workers exposed to the soot of oil fuel, which ment. The Industrial Injuries Act of 1946 is thought to be caused by the high percent removed the responsibility for compensation age of vanadium in the soot. from employers and insurance companies to the Government. Since then cases taken SUMMARY under Common Law against the employers The position as regards the dust diseases have increased rapidly. in Great Britain may be summarized as fol 4. Numerous legal provisions, contained lows: both in Acts of Parliament and in Regula 1. During the past 50 years, the risk of sili tions, have been brought into force. Routine cosis in most of the major industries has been inspection by inspectors of factories and firmly established. Until the late 1920's, free mines has been instrumental in limiting the silica was the only dust which was thought numbers of cases of disability and death to damage the lungs. Ashestosis, caused by brought about by inhalation of the dangerous the dust of a combined silica mineral, came dusts. into prominence about that time. In the mid 5. It Is expected that more accurate infor dle 1930's, attention was given to the effects mation about the incidence of the dust dis of other dusts on the Jungs, such as iron and eases will be obtained in the near future, its oxides, and of radiopaque dusts, china when statistical studies of the information riay, yUimamtc, kieselguhr, tak, and meted obtained by the Pneumoconiosis Panels have dusts containing free silica. been carried out, and when the report of the During the middle 3930's also, the effects Registrar-General about the occupational of coal dusts on the lungs were given increas inddeace of disease at die time of the 1951 ing attention, and extensive surveys were Census becomes available. At the present carried out, culminating in the formation of time no reliable information exists about the Pneumoconiosis Research Unit of the the populations at risk in each industry and Medical Research Council m 1945. The coal process, miners numerically constitute the greatest 6. Surveys of the population by mass radi problem of dust disease in Great Britain. ography to detect early tuberculosis are 2. Despite the combined efforts of inspec bringing to light information about the ef tors of factories aral rouses, physicians, ebero- fects oi dust to some hitherto unsuspected sists, engineers, and research workers, die occupations, deaths from pneumoconiosis have continued 7. Many problems about dusts and the to rise yearly. The reasons for this increase may be found in more accurate diagnosis of the condition and in the publicity given to lungs are still unsolved, and some would say that wo have only just begun to attack the fringes of the problem. Nevertheless, a great occupational diseases of the lungs, leading to deal has already been accomplished. more frequent mention of pneumoconiosis by /physicians on death certificates. But a more likely cause is the urge for increased speed of Assistance in compiling the information con tained in this paper was rendered by Dr. P. K. Walker and the members -of the Pneumoconiosis production, and the introduction of machines Panels of the iiinistry of Pensions and National Insurance; Drs. E. R. A. Merewether, A. T. Doig. | Doig, A. T.: Unpublished da*a. and G. O. Williams, of the Factory Department. $6 BUST DISEASES IN GREAT BRITAIN Ministry of Laboar and National Service; Dr. H. E. Harding, body { Sheffield University, and Dr. G. NageUdanxjdt of the Safety in Mines Research Laboratories, Sheffield. BIBLIOGRAPHY Arlidge,}, T.r Hyjpene. Diseases., and Mortality of Occupations, london, PerdraJ & Co., 1891 Campbell, J. M.: Acute Symptom* Following Work with Hay. Brit M. J. It1143, 1932. Cajtlede*, L L M., and HaowJfon-Pawrson, J. 1_: Sagassosa*: As Industrial Lung Disease, Rrit M. J. *:4?8, 1942, OMKs, E. L.: Industrial prwumonoconiosis, with Sgedaf Refermce ?> Dojf-Pwhisii, PdL Health *8:252, 1914-X91S. Cooke, W. E.: Pulmonary Asbestosis, Brit M. J. >51024,1927. Craw, /.; B/ood Examinations in Pofnwnary Rh-frah of Haematite Iron Ore Miners, Tubercle 19:8, 193?. Control and Etiaunatian of Silicosis is the West Coast Haematite Iron Ort hxUxtr?, Brit J. !adust Med-4'-SO, 1947. Davies, T.A.L! Manganese Pneumonitis, Brit J. Indust Med. 8:113. 1946. ----- and Harding, H. E : Manganese Pneumonitis; Further Chnlcal and Experimental Observa tions, Brit I. Indus*. Med. 4:62,1949. Doig, A. T, and McLaughlin, A. I. G.: X-Ray Ap pearances of if?t Ltmgt of Efeetrie An Wel ders, Lancet 1*771,1936. Clearing of X-Ray Shadows >o Wriders' Skkr* osis, Lancet 1:789,1948. Dreessen, W. C: Effects of Certain SiHcate Dtuts on the Lung!, J. Indust Hyg. 18:66,1933. ... and Dalla Valle, J. M-: Effects of Exposure to Dust in Two Georgia Tak Mills and Mines, Pab. Health Rep, S0:13I, 3935. Dunner, L-: Observations on Pulmonary Disease to Graphite Workers, Brit J. Radiol. 18:33, 1945. Observations on the Development of Graphite Poeomoeorriosis, Brit, J, Radiol. >1:182, 1948. ----- Herroos, It, and Bagrat), D. J. T,; Ptmwjo* eooksis in Dockers Dealing with Grain and So**, Brit l RaSol *9.-$06, JW6. ----- and BagnsJl, D. }. T.: Pneumoconiosis Is Graphite Workers, Brit J. Radiol. 22:573, 1949. fawertt, R.: FiatgoM Conditions d the Lungs, Brit. J. Radio!. 9:172 and 394, 1936. Occupational Diseases of the Lungs in Agri cultural Workers, Brit ). Radiol. 11:378,1938. Giftison, J. A, and Tayht, >*.: Bagaitoih: Further Notes of Fcur Cases, Brit. M. J. 2:577, 1942. Gkya* S. XL: Presence of lie Asbestos Fiber in the Lesions of Asbestos Workers, Tubercle 18: 404, 3929. -------Marshafl, GH and Hoyle, C: S*tKuatosoniosU Due to Graphite Dast, Thorax 4:31,1949. Grce$how, E. H.; Report of Medical Officer of the Local Government Board, Appendices IV and VI, t86G-l86l. Haldane, J. S.; Marint J. $, and Thomas, R. A-: Report to Secretary of State for the Home Department on fee Health of Cornish Miners, Cbnvnand Report 209}, 3J> M. Stationer? Office, London, 1904. Harding. H. E-; Tod, D. L. M,, and McLaughlin, A. I. G.: Disease of Longs in Boiler Scalers, IVitir a Case Report and Review of Literature, Brit J. Indust Med. 1:247, 1944. Pnras&oconiotis in a Boiler Sealer, Brit J. Infest Med. 4:100, 1947. ------- aod Oliver, C. B.; Changes in Lungs Produced by Natural Graphite, Brit J. Xndast Med 8: 91, 3949. Hart, P. D'A, and Aslett, R. A.: Chrtxtk PuL ntoffaryr Disease so Scvtb Wales Coahrunert Special Report 243, Medical Research Council, tendon, 1942. Histfcr, D., and Perry, K. M. A.: Bronchiolitis Resulting from the Handling of Bagasse, Brit I. Indust Med. 8:64, 1946. McDonald, 8.: Histology of Pulmonary Asbestoax, Brit. W. J. 2:102$. 3927. McLughfio, A L G.; Grwt )* l- A.; Barrie, H. 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Med. 8:127, 1951. 97 UcLAVGHUN Development of Compensation for Occupational Diseases of tbe 'Longs b Great Brftax^.Brit. j. Induct Med. 11:198, 1954. Uerewetber, E. R. A.: Annual Report, CHef In spector of Factories, London, p. 63, 1933, and *. 3?, W54. Risk of SilicosU jn Sandblasters, Tubercle 1?: 385, 193d. --and Price, C. W<: Report on Effects of As bestos Dust on tbe Lungs and Dust Suppression in the Asbestos Industry, H, M. Stationery Office, London, 1930. Middleton, E. L>: Industrial Pulmonary Disease Due to the Inhalation of Dust, with Special Reftm** to S&ten%, Lames* lv\ j*6 S3, V>36, Peacock, T. B-: Diseases of the Organs of Respiration, Tr. Path. Soc. London 12:36, 1861. Pearson, G.: Philos. Tr, London, 198:259, 1813. Pneumoconiosis Statistics for 1953, Digest of, Ministry of Fuel and Power, M. M. Stationery Office, London, 1954, RiddeH, A. It: SUkosis: Studies and Reposts of L L. O. (Series F, 17), Geneva, p. 39,1940. Schilling, R. S, F.: Byssmosis in tlie Lancashire Cotton Industry, Tr. A. Indust M. Off, 4:61, 1954. Siegal, IV.; Smith, A R., and Gre-enbiifg, L.: Dust Haaard m TrcrooSile Talc Mining. Including Roentgenological Findings in Tsk Workers, Am J, Roentgenol 49:12, 1943. Sjoberg, $. G,: Vanadium PentoxMe (V*0*) In toxication, Nord. mecl 41:500, 1949. Stewart, M, j. and Haddow, A C.: /. Path, k Baet 12:172, 1929. -- and FauJds, J. S.: Pulmonary Fibrosis of Haematite Miners, J. Path, fr Bad. 89:233, 3934. Sutherland, C L, and Bryson, S.: Report on Occurrence of Silicosis Among Sandstone Workers, Mines Department, H. M. Stationery Office, London, 3929. Report on the Occurrence of Silteosu Among Granite Workers, H. M, Stationary Office, London, 1930, Tbackrah, C. T-: Effects of Arts, Trades, and Pro fessions, apd of Cmc States and Habits of Living, on Health and Longevity, Ed. 2, Lon don, Longman, 1832. Williams, N.: Vanadium Poisoning from Cleaning Oil-Fired Boilers, Brit J, Induct Med, 9:50, 1952. Wood, W. B, and Gloyne, S. R.: Pulmonary Asbestous: A Review of One Hundred Cases. Lancet 2:1383, 3934. Wyers, H.: Some Toxic Effects of Vanadium Pentoxide, Brit J. Indust Med. 8:177, 1946. Asbestosis, Postgrad. U. J, 28:631, 1949, ' < .K (Clearance of f^adiocLctive 2)u^t front the ^JJuman oCurup ItOV L AJJfHT, KD, Wfcf*w. B. C. end UVftENCI C ARNETT, M.D* fcoeMr* One of the important potential health haz ards associated with the atomic energy in dustry is that of air-borne radioactive dust. This ii set s new problem, since radium and uranium mines have always had radioactive dust and radon gas. Indeed, the only prac tical experience with this hazard originated in the European uranium mines, where there was an extremely high incidence of lung cancer.' The control of radioactive dust is in one sense as economic matter, because the greater the expenditure for ventilation equip ment the less the degree of personnel ex posure. The problem then has been to estab lish reasonable levels of exposure which would insure safety of the workers without being overly conservative and therefore too expensive. Two approaches to this problem have been made. The known average con centration of radon <3X10"* curies/Jiter) in the Schseeberg and Joaehimstal mines has been used as the basis for a recommended maximum permissible concentration of 10*1' curies/littr* In practice, however, tCr*8 curies/liter has been used to a considerable extent. The other approach to the problem of establishing safe working concentrations is based on a maximum permissible radiation dosage rate to, the lung of 300 millirem/weefc.* An estimate is made of the air concentration of the particular dust in ques tion which if inhaled over the period of a working week would deliver this radiation Recorded for pnbSication April 7, 1955. dosage to the lung. It is pertinent to note that the value of 300 milljrem/week is also used for whole-body exposure to penetrating radiation and is derived from estimates of the dose which would not be damaging to the blood-forming organs.4 Whether it is reason able to utilise the same permissible dosage for both the lung and the blood is not answerafete at the present time. It is of interest to compare the dose rate of 300 miliifem/week with that calculated for the maximum permissible exposure to radon, Harley 4 has calculated that exposure to 10*'4 curies/Utcr, assuming 50% retention of the radon daughter products on the bron chial epithelium, would deliver 50 rem/week. This is 150 times higher than the 300 millircro/week permissible value. This calcula tion must be tempered by the lack of infor mation on the actual fraction of inhaled radon dai^hter products deposited on the bronchial mucosa and the question of whether the radon or thotoo daughters, in fact, remain in the lung or become rapidly dissipated to the blood stream. This Utter point, that of the effective half-life of the daughters of radioactive gases, forms the subject of some experiments to be reported here. Although the dosages from the current maximum permissible concentration of radon and the maximum permissible exposure rate to the lung of 300 raiflirem/week do not com pare very closely, it is well to point out that the use of the more conservative value in volves a number of assumptions which are, at best, crude approximations. For example, one must assume that a certain fraction of the inhaled, dust is retained and that this retained dust has a biological half-life of a certain magnitude. These factors, together 99 ALBERT AND ARNETT with the radiological half-life susd the effec tive energy of t1 emitted radiation, enable one to calculate the permissible air-borne concentrations. There may be a major feUacy in this approach, since most of the lung can cers observed in the European uranium mines, and these presumably were due to radiation, occurred in the epithelium ofmajor bronchi. The walls of Such bronchi are suffi ciently thick to prevent the penetration of the alpha and beta radiations (which are the im portant ones so far as lung damage is con cerned) from the outside of the bronchial wall through to the inner lining, which is the target organ in question. Consequently, radiation to the bronchial mucosa must orig inate largely from the particles which are initially deposited in the bronchi or which are swept out over them by the ciliary mech anism. From this point of view, the radio active particles which are rapidly removed from the lung constitute the real ha2ard. The estimates for the maximum permissible air concentration are, however, based on the fraction which remains behind in the long, and, for all we know, this material deposited in the alveoli may be rendered harmless by the comparative radioresistance of the alve olar structures. This, in one sense, would be analogous to the situation in which lead is detoxified by being deposited In the skeleton and its damaging effects occur while in transit to and from the bone. If this, in fact, is the truer picture of the situation, the bet ter estimate of the harard would involve in formation on the fraction of inhaled radioactive particles which are deposited on the bronchial mucosa and the rate at which they are removed. It is this point, namely, the speed with which radioactive particles are removed by ciliary action, that constitutes the subject of the second group of experinwnts to be reported here. EFFECTIVE BIOLOGICAL HALF-LIFE OF TJfOftOH DAUGHTERS t As indicated in Figure 1, the daughters of thoron gas are more suitable than those of radon for the estimation of the effective half- life in the lung, because they have a radiologi- cal half-life of about 10# hours, compared with 30 minutes for radon daughters. In addirion, ThC and ThC have gamma radia tions of greater than 1,000,000 electron volts, which make their detection from the outside surface of the chest feasible. In these studies, thoron gas was dispersed into a 1000 cu. ft. chamber by bubbling air vigorously through a 2 me solution of ThX. At the same time a cloud of kaolin (alumi num silicate, H*A!aSia&, density 2.1) dust was maintained in the same chamber. After the thoron supply to the room is shut off. Fig. I.--Thorium decay series. ThA, with a half-life of 0.16 second, decays almost immediately and the remaining activ ity is governed by ThB, with a hall-life of 10.6 hours. The thoron daughters are pro duced in atomic form or io very small aggre gates, and they adsorb onto the surfaces of suspended dust and are deposited in the lung with the carrier dust. Since they are attached to the dust in a tenuous fashion, wc were interested in determining whether the daugh ters were quickly washed off and carried away from the Jung by the blood. 100 CLEARANCE OF RADIOACTIVE DVST FROM LONG A concentration of 10** curies/liter of ThB was maintained throughout the experiments, of which six were performed os four healthy subjects. The dust was inhaled for approxi mately one hour through a face mask at tached hf a short length of rubber hosing to a port in tlie dust chamber. Cascade-impactor samples were taken during the early and Utter parts of the breathing period. When the subject completed the dust mhala tion, he washed his face and removed any dust from the pharynx and mouth by gar gling. He then seated himself before a scin- The results of these studies are presented in Figure 2, where the experiments were di vided into two groups on the basis of the initial count rate recorded from the surface of the chest. It can be seen that the effective half-life, as determined from both curves, was aboat nine hours. This value is very close to the radiological half-life of 10,6 hours, indicating that the biological half-life is in the order of 60 hours. This study indi cates that, once deposited, the thoron daugh ter produets, and by analogy radon daughter products (because their chemical forms are Pig, 2,--Net gamma count rate from the surface of ike chest following inhalation ot thoron daughters. til&tion counter which utilized a cylindrical sodium iodide crystal, 2 in. in diameter and l *4 in. thick. This crystal was mounted in a lead shield in such a manner that the front of the crystal could be pressed against the subject's chest. During all experiments the crystal was positioned on the anterior surface of the thorax on the midJ/ne at the kvei of the second rib. The crystal received the gamma radiations emitted by ThC and ThC". The. particle-size distribution of the kaolin dust was quite uniform and ranged in all the experiments from 1,1^ to 1-V massmedian diameter. almost identical), are removed slowly enough so that the effective half-life is not signifi cantly different from the rate of radiological decay. CLEARANCE RATE OF DUST BY THE CILIARY* MECHANISM As indicated previously, the hazard of in haled radioactive insoluble dust may come from those particles which arc removed by ciliary action rather than from the ones re maining behind, and it was of interest to determine the rate of this removal in humans. Animal studies have indicated that the linear 10! ALBERT AND ARNETT velocity of particles carried on the bronchial mucosa is quite high, shout l ter-3 cm. per minute, depending on the portion of the respiratory tract. In addition, it Is common experience of radiologists that iodized oil (Lipiodo!) used for bronchography is fre quently removed within one day. Animal studies utilising radioactive dusts also indi cate that the bronchial mucosa is cleared in a matter of hours.' For these studies, metallic iron powder was used, which had been irradiated with Biendor was turned on for three seconds, and at die end of th interval she subject was instructed to take a breath; at the same time a caseade-isnpzctor sample was ob tained. The Bkndof was turned off, and the subject rinsed his mouth and pilarynx by gargling with water and then went quickly to the sriwiilatw) counter, as described be fore. ht the experiments to be reported here, eight studies were performed, four with par- Fig. 3,'--Net gamma count rate from the surface of the chest fb/fowitTf iabafafioQ ol rediozctive iron dust in Subject A. B. neutrons in an atomic pile to produce a radioactivity level of tOfyic of Few per gram of iron. This iron isotope has a strong gamma component and consequently is also suitable for detection from the surface of the chest, The radioactive iron powder was placed in a Waring Bfendor wWcft was fitted with a tight cover. The cover had an opening for a short breathing pipe attd a part hr the inlet of a cascade impaetor. At the beginning of the experiment, the sabject placed his mouth around the breathing pipe. The m ticle sizes of 3.4*r-4,,V and four with partWe sires of 1.4p*2V mass-median diameter. Three of the four studies with the larger particle sizes were remarkably similar. Fig ure 3 illustrates an experiment in which the count rate from the surface of the chest started at about 2CQ0 counts per minute, rose rapidly several hundred counts more, and fell precipitously to about Sffc oi the initial activity in two hours. Figure 4 presents a similar response in another subject. During the coarse of this run, it occurred to us that the activity which was lost from the chest CLEARANCE Of RADIOACTIVE DUST FROM LUNC ONB F. 4.--Net gamma count rate front the surface of the chest blowing mbtltefar d radioactive iron dust in Subject ft, A. should appear in the .abdomen, because par ticles raised fey rifiary activity are swalfowed. When the subject pkced his abdomen against the crystal at about the level of the umbilicus, the indicated high count rate was observed. A saline cathartic was administered, after two defecations the count fell to very low levels. Blood samples taken during the pe riod of rapid clearance from the chest indi cated no detectable radioactivity. The next subject (Fig. 5) was unusual. Whereas the other subjects achieved a high chest count with one respiration, this subject had to inhale about four times in order to reach a counting rate of only 300 per minute, In retrospect, the subject recalled that while breathing he had kept his tongxee dose to the hard palate. It is possible that because of the narrowing of the breathing passage through the mouth, the velocity of the air Fig. 5.-->ier gamma count rate from the surface of the chest following inhalation of radio active Iron dost in Subject L. A. or AsscMiKAt. eccms^iraam BOTW >3 103 ALBERT AND ARNETT activity and then dropped more slowly to a level of about 12% in eight hours. In this experiment, serial abdominal counts indi cated that the activity in the abdomen fol lowed the chest activity inversely, and, as in the previous run, die activity returned to FJg, &---Net gamma couni rate from the surface of the chest following inhalation of radioactive iron dust tn Subject M. W. 4 wjhiaJ - * *N became high enough in the pharynx so tot k*" TM lung, and of those At did **' , greater *ed the In any event, this sdH* *S*Hl ,K. initial rapid drop in <*" w**` the fall, stepped at 1ut 25?*' "1 **'* lntt"1 i' tw.r background levels only after several bowel evacuations. The response to the smaller particles is illustrated by Figure 6. Here we see that there is again a rapid initial fall, in this case m 4 hours to about 60% of the initial activ ity, and then a slower fall over the course of 30 hours to a level which is thereafter sus tained for the remainder of the observation period of 70 days. It is worth noting (Fig. 7) that in two subjects receiving the smaller particles the secondary 3CM*our clearance period appeared to consist of two parts, with Ftg. 7,--Net gamma count rale from the surface of the chest following inhalation of radioactive won dust in Subject E, H. * 4 ') * ** 104 CLEARANCE Of RADIOACTIVE DUST FROM LUNG * more rapid initial phase which resembled the secondary clearance in subjects receiving the larger particles (Figs. 4 and 5). . la summarizing the data in Figure 8, the average time for completion of the first decay cam to the four experiments with the larger particle sizes, was 2.1 hours, with a range of J.9 to 2.3 hours, and the average percent;a|fc'bf the material cleared from the lung ;fter.this period was 87%, with a range of \ 75% do 95%. In two of these subjects, there jwas', a^second clearance period, lasting 32 COMMENT The technique of measuring the clearance of radioactive particles from the lung, as used in these studies, is sensitive to changes in geometrical distribution of radioactivity within the chest, but the interpretations of the data, as reported here, would not be seriously affected by this factor. The results obtained with the thoron daughter experiments are probably more representative of particles deposited mainly in the alveoli, and consequently it is still V -V PARTICt* ' . -5% V. SEE r; * * '.' 's. MUD K &k*. S.S i.n *; . VTBST tJECAY PERIOD, pears).. ./ CtEA 2.V / * to 'S&lV 3.5 2.12 i: " 88 W. D. s. a 3.72 2.3 25 1L A. u 1.72 2.6 75 AVE. 2.1 ST SECOND DECAY'PERIOD `(hours) % , CLEARED .. . ... ... 3.2 ... 5.5 25 ... 68 hf. . 2.2 1.70 4.0 26 31 62 U. . 2.2 1.94 2.6 47 36 62 H. o. 1.4 1.70 2.4 S3 33 75 E. R. 1.6 1.67 2.0 S 32 64 AVE. 2.4 ? S3 Fig. 8.--Summary data as inhalation of radioactive iron dent. S and 6.5 hours, which reduced the retention about another 10%. In the four experiments where the subjects inhaled the smaller particle sizes, the average time for completion of the first clearance period was 2.4 hours, with a range of 1.6 to 4.0 hours, and the average activity cleared from the chest after this period was 47%, with a range of 36% to 53%. All these sub jects exhibited a second, shallower clearance slope which ended in an average of 33 hours, with a range of 31 to 36 hours. This second clearance period increased the lung clearance from an average of 47% to 68%. moot whether radon or thoron daughters would be cleared by the ciliary mechanism. It is wortk"botiag that, because the radio active daughters are fixed onto the surfaces of particles, their distribution in a dust cloud will tend toward the smaller particles, where the surface area is greatest, and these are the ones which would tend to be deposited in the alveoli, This is to be contrasted with the radioactive iron particles, in which the amount of radioactivity is a function of mass rather than of surface area. There is little doubt that the initial rapid removal of the radioactive iron from the 105 ALBEXT AND AXNB7T lung represented aliary clearance. MetgEcc iron is an insoluble material, attd the trans location of Jhe radioactivity to the intestine and the lack of appearance in the blood were convincing evidence that the iron was not solubilized to any extent and thus removed from the lung. The speed with which the ciliary mechanism cleanses the bronchial mucosa would appear to make this a very effective means of minimizing radiation dam age to the bronchial epithelium, The tech nique by which this has been demonstrated in humans could no doubt be extended to provide further information on the relation ship of particle size to bronchial deposition, SUM MAS* The effective half-life of thoron daughters in the lung following deposition, together with kaolin particles of mass-median diam eter i% about nine hours. This indicates that the pulmonary clearance of radon and thoron daughters under these con ditions will oot materially reduce the radia tion hazard following inhalation. The early bronchial clearance of radio active iron particles appears to have two phases: The first clearance period ends m 2 to 4 hours and the second in about 30 hours. The larger the average mlialed par ticle size, the greater the fraction removed in two to four liours. U. S. Atomic Energy Commission (Dr. Albert). 693 Madison St. <Dr. Amen), REFERENCES 1. Pirchan. A., and Siki, H.: Cancer of the Lung in Miners of Jarhymov (Joacftumtai): Re port of Cas Observed in 1929-1930, Am, J. Can cer U-.m, 1932. 2. Evans, R. D and Good&tan> C: Detemmatkm of the Therm Content of Air and its Swriofi on Lung Cancer Hasards in Industry, J. lodust Hyg. * Toxkd, :89, 1940, 3. Maximum Permissible Amounts of Radio isotopes (he Human Body and Maximum PerDissibk Concentrations in Air and Water, Hand book 52, V. S, Department of Commerce, National Bureau of Standards, 1953. 4. Stone, R S.: Concept of a Maximum Perruissible Exposure, Radiology 58:639, 1952. 5. ttartey, }, H.: Study of the Awfcornt Daugh ter Products of Radon and Tboron. Thesis, Reiswiser Polytechnic Institute, 1952. 6. Barely, A. EL, ami FraaW/n, K. Reflexes fran the Bladder and Large lotesime, J. Physiol. M:47. 1937. 7. Scott, K. G,; Axelrod, D.; Crowfey, S-, and Hamilton, J. G.: Deposition and Fate o( Plutonium, Uranium, and Their Fission Products Inhaled as Aerosols by Rats and Man, Arch. Path. 48:31, 1949, * *. '*.. Olte ^hitacfonifitic ddioioqicaisection Quartz and PotaA&ium Carbonate Afl CapetWaM Sedy * Pyi G. W. H.$CHE?01S( M.D.,S>.$*. esj A. B. DEtAHANT, Seranoc Lak, N. Y. One of the major catastrophes of the silica industry was first recorded 2S years ago, when Koch * reported an acute silicosis re* salting Irom the inhalation of fine quartz dust mixed with alkalies. Since that date a siate of similar occurrences have been re* ported from afl over the industrial world.* In the majority of instances, the incriminat* iag exposures were experienced in connec tion with the manufacture of scouring pow* ders, and one of ufe (G. W. H. S.) has seen several instances in South Africa. Ia most of these cases, the silicosis was of an aberrant type and characterized by the rapid appear ance of massive confluent fibroceliular lesions and marked hilar periadenitis. The disease proved fatal in less than two years in a large proportion of cases, and in some instances the victims died within a matter of weeks.* Abnormal susceptibility did not appear to play a part in provoking this malignant reaction. In Rossmg's u scries, for instance, all employees were affected withm a space of seven years. The terminal complication in the majority of reported cases appeared to he cor pulmonale or tuberculosis, but it is Recorded for ptrMtcai'on June 28, 1555. Director {Dr. Schrj'ers) and Research Associate {Mr. Delahant), The Saranac Laboratory. References 2-11. remarkable that tuberculosis played no role in the early pathogenesis of the disease. Owing to the often rapidly spreading nature of the radiographic shadow, the attendant malaise and toxemia, the frequent appearance of miliary shadowing, and, in some instances, dissemination of the process to extrathoraeje organs, such as the liver or spleen,' tuber culosis was frequently diagnosed in error until autopsy provided the final answer. In some cases the quartz Hour was mixed with diatomit* and kaolin,1* thus confusing the issue. However, id the majority of cases, the combination of quartz flour with an alkali (m the form of soda) was the only factor to contend with. The alkali content ranged from 2<fo18 to 25$>. Soon the theory that the alkali had increased the solubility of the quart2 became widely accepted. Kettle1* opposed this concept on chemical grounds and Lochtkemper and Telcky** drew attention to the fact that in their clin ical experience with a sandpaper industry the addition of varying quantities of alkali produced no significant additional danger over that which couM result from compar able exposures to pure quartz dust generated in a quartz mtft The suggestion would stem to be, therefore, that it is the fineness and purity of the quartz flour, together with massive exposures, rather than the addition of the alkali, which provoked the overwhelm ing pulmonary reaction. It is clear that this type of problem would be settled only by the experimental method. There is no record of any systematic investigation in thi9 diree- 107 SCHEPERS AND DELAHANT tion, though The Saranac Laboratory did experiment with one of the soap powders and failed to obtain any fibrotidyespouse. It is with considerable interest, therefore, that among the uncompleted labors of the late Dr. L. U. Gardner a briel relevant experi ment, in which one of us (A. B, 0,) parti cipated. could be found. In this study a mixture of quarts dust, potassium carbonate, and carbon in the fol lowing proportions Quartz 61 KiCO. StS% Charcoal (3* aad less) 0Ji% was introduced intratrachealiy into the guinea pig lungs and iDtraperitoneaJIy. The mix ture was injected into the trachea in nine animals in two doses of 0.5 cc of a 10% suspension at weekly intervals. Thus a total dose of ICO mg. per animal was administered. For the iatraperitoneal injections, pairs of guinea pigs each received 2 cc. of a suspen sion of the mixture. The strength of the suspension, which was different for each pair of animals, was 10%, 7%, S%. 2%, and 0.5%. OBSERVATIONS In Tables 1 and 2 the results of these experiments are summarized, It will be seen that five of the nine animals in the Intra tracheal experiment died of pneumonia. Whether or not this was due to an iatercurrent infection was not established. The occurrence of the first three deaths within the first six weeks suggests a causal relation between the deaths and the acute tissue response to tlw injected mixture. However, animals succumbing to toxic factors in an injected dust usually do so within a shorter period, and the deaths may possibly be co incidental, To substantiate this postulate reference to the records of The Saranac Laboratory at the time of inception of the present experiment revealed that an epizo otic was rampant at that time. The initial conspicuous lesions produced in the lungs of these animals are quite in conformity with the results to be expected oh The introduction of moderately irritative 30 Table i.--Puhnottary Effects of Intratraekeai Infections of e 3: 2 Adnusture of Quarts Dust end Potassium Carbonate Ely* QnultS,N i*clljJ- DM* or No. 002 KBM3 USD 4KD S *1 D 1 *0 S t uOS SO lift D t 9U D 1 KB It B m& Grou Pua&oaarr Beccetoe GukaefidtifoB lett *odl lot* ftogta lirce Ir* eea*ifiSDmU latoo. wtu> pkunl taMUos w*U eouaMattea of rtgbt wt*B lot*; tarv firs Mortomut* Moo. wteta ersrlylM BObetaos l4ft soartosmit* tedoo, *fU> be**r fttaurml ptrnuaUUoa ebSteretire pfcvrfttt lAne oMulodtmt* tatfoa, wft& evulyfez tdbeiloo VoXibUbou* lusii, vftb t tow* e>rat stsu io left raudu ; ncuatitfe f'tl obeoft. Wt 6e*tfc lad wtaefc at dual natHua BpesUaaeaa nubi* tad staenU cSwatoo. wits largo eatleua* * taaioa LaMrro*np,itwalniiwee*arUaomttformt ena ptawritu Two larro Naalr sett wactoacr* at* taataas * AB apoBUowooa dattti* were do* to poopnutria foreign matter. The point of greatest rele vance concerns the fact that the masses provoked did not increase in size, become indurated, or undergo necrosis even after 575 days. The response to an equal dose of quartz atone would, at a commensurate stage, have been an unequivocally progres sive sclerotic affair. The peritoneal reaction parallels this pul monary response (Table 2). The deaths from the 10% and 7% suspensions in die early phases of the experiment were un doubtedly due to the toxic action of tbe injected SiO* plus KjCOj mixture. The lesions were instances of classical chemical peritonitis. Guinea Fig 55, however, shows that this peritonitis was sot invariably fatal, leading to partial recovery. The lesions found in the remaining animals may all be clas sified as benign m comparison with those ordinarily to be expected from quartz alone in an equivalent dosage. The analysis of the pulmonary histopathotogy elucidated the whole problem. The immediate effect of the introduction of this blend of quartz and potassium carbonate was ANTAGONISTIC ACTION OF QUARTZ AND POTASSIUM CARBONATE Tails 7---Effect of fiUraptrito*eal IttjecHotu of o 3:2 Mixture of Qwts end Peta*si*m Corbonoit Oosctttn. (feeefSe*. **0*08.* Osis** JPUt DUder ObMrvfttfen* M V ft : St to t 1 - to 60 ( ft r a u 1 ) i* IS ao m UO iso 10 HO t> l i D D K K D V s K BareuficafeMMu a*a via leuea* <UatcB<M tom* ao t*crk: Oaterftaai fioM; botO pitmmted aan Pateosar? atctetaM; aWoatBul bub wIUi bs*J eoHJftsaQv* MUMf* Planle psttootta vltb *a mam* Bats oon peritonea! pUoad; thktomlnf o! omotaas Snaa aolt peMconMj pluoe**; enema! Beal adbotoos wIUj lalal MxtrvetioB Matted adaaB&at ot *7>ftoid tod Mstttso: died Iron redeot PcrltBMU 804 Oftatll ftUffM Seal adfeeatess; taoU&fc ojwsuJ Mit dost depoata 'a t <7 ao no * *1 */ Slofle cnal toft pnltoeeal p1m* aad uaaB oaaaui ton depoilt* aralfiok 94 -U n 118 1} Isolated amlttpte iwnanul dort dcooiiu to produce marked and universal cylological reaction.. By 4he end of three days very little pig ment ,,wa* .preserved within the lungs and all of it.was found intraccllularly. Some of the dust had also been transferred to the hilar lymph nodes. The characteristic lesion consisted of a diffuse alveolar wall thickening caused by capillary distention, proliferation of scptnl or mural cells, and infiltration of these walls by numerous macrophages and fibroblasts, many of the former being pigment-laden. Lying free within the alveoli there were numerous macrophages and multimicleated giant cells. These cells were charged with dust particles and tended to be in contact with the alveolar walls. Some of the giants were so large as to occupy some alveoli completely. The abundance of macrophages and fibro blasts was particularly marked around the smaller blood vessels and bronchioles. The epithelium of the respiratorypassages showed some swelling and regional superficial necro sis, which became a more constant feature in the smaller ramifications, where copious desquamatory matter occurred in the himina. The smaller Wood vessels likewise were found ensheathed in prominent cellular cuffs, and their muscular layers showed hyper trophy even within the lymph nodes (Fig.I). At the end of 400 days, the essential lesion still persisted as a cellular hyperplasia of all components of the lung tissue. Regionally the infiltration of the alveolar walls was so abundant that confluence might be simu lated, especially where numerous macro phages were present within the alveoli (Fig. 2A). This effect was enhanced in some areas and simulated at others through marked regional atrophy of alveolar spaces in which dust-filled macrophages and giant cells tended to collect (Fig. 2B). These atelectatic parts of the lung may be topo graphically related to foci of bronchitis and obliterative bronchiolitis, which were ob served at separate points. Atrophic vesicular emphysema was ap parent throughout both lung fields (Fig. 2). There was a distinct decrease in tbe vascular ity of the parenchyma because of the partial obstruction of smaller blood vessels by the proliferated cells around them or composing their walls. In some of the animals killed after 575 days, condensations of the dust were found at isolated foci (Fig. 3^). These areas consisted of pigment-filled atrophic alveoli, and there was no significant cellular reaction in relation to these areas and no fibrosis. These conglomerate masses of pigment with supporting stroma comprised of the residua of alveolar walls were contained in giant macrophages. . 109 SCHEPERS AND DELAhANT p. .. Inhibitory action of potassium carbonate on Quartz: guinea pig, 32-day result A, Tt( ' , Illustrates marked cellular proliferation, with macrophage catarrh and alveolar wall 8, lymph node; macrophage mfilrrariatr of medolfe. without necrotK cr 9e*rnw --. - jiu&ycd combined effect of quartz and potassium carbonate; guinea pig, 400day j *l4leural region with dast-laden macrophages and giant cells trapped in cortical atrophic emphysema, B. atelectatic parabrorvchial zone, with retained intracellular ANTAGONISTIC ACTION OFj QUARTZ AND POTASSIUM CARBONATE K*. 3--Residual lesions resuming from the intratracheal bjection of quart? and potassium carbonate in a 3 : 2 ratio: guinea pig, 575-day resuh. A, hmg: parenchymal focus with dust trapped within aizoplilc alveoli: no residual, rettfoiud, *)hilar, or fibrotJe reaction. B, lymph node: persisting dust-laden macrophages tn medulla, without associated fihrogenesis. The lymph nodes still showed marked macrophage and giant cell infiltration into r tbc mcdulla at this stage. Whole islands of such cells were found within distended lymph sinuses (Fig, SB). Sighs 'oi fibrosis could first be discerned m (he lungs oi this last group of guinea pigs, it was sparsely laid down and mainly perivascular in distribution. Some of the * alveolar-watts were fibrotic and avascular, and the atrophic emphysema had advanced a little further in some areas. On the whole, however, there were fewer komophores in the alveoli. Io the lymph nodes, too, the macropliagcs - had mor^or less disappeared, leaving behind central collections of opaque pigment. From these microscopic features it is clear, therefore, that the combination of potassium carbonate w ith quartz in a 3 to 2 ratio, with a trace of charcoal added, nulli fied to a large extent the fibrogenic pro pensity of the quam and no silicotic nodule* developed, though some diffuse minimal alve olar wall and vascular damage, bronchiolitis, and emphysema persisted. The peritoneal histological features were in complete conformity with the reaction to transiently irritating foreign substances. In these animals that died of a chemical peri tonitis as a result of the introduction of the 10% suspension, the inflammatory reaction was subacute in degree, without any necro sis. The subperitoneal masses which formed in the animals receiving tbc 7% suspension were unlike those associated with quartz dust, being limited to monocytic and isolated giant cell infiltrations and occasional initial minimal leucocytosis. This benign cellular reaction persisted to tlje end of the 160th day. The reactions to the 5%. 2%, and 0.5% suspensions of the quartz-potassium carbo nate mixture were limited to monocytic infil tration, without giant cell formation or necrosis. These lesions showed no significant regression after 120 days but also gave no indication of aggravation or fibrosis. HI * v SCfJEPERS AND DELAHANT COMMENT a Pyrex flask in the icebox for four days. While die tissue reaction to this mixture of dusts cannot be classified as completely inert, there is no doubt thatihe quart* had "Soluble" silica was then determined colonmetrically by the phcsphomolybdie add method. The results were as follows: been inhibited in respect of its most charac teristic propensity, e., the capacity to pro voke fibrosis. To be precise, some fibroblasts were detectable within the cellular lesions at the end of the first month, and fibrosis of a OoquMSa< CottWM* Me**.,.................... ............... a*ft* rt% ud gC0 su%.............. is Quartzes................... 14 EOC. ms% .......................... Fra KM taj 1T. SO.tUA limited degree was discernible in animals at the end of 575 days; but this reaction was no more than what cousd be found in the pres ence of so-called inert dust lesions and by no means comparable to the marked sclerosis induced by pure quartz. The value of 512 for the K2COg alone prob ably represents the amount of SiOi dis solved from the glass. Subtracting this value from that for the complete blend yields a net "soluble" silica for the latter of 227.9 ppm. The faculty of quartz to bring about focal necrosis was in equal measure suppressed. it is not yet certain whether the fiferogenic propensity of quart* is not perhaps linked to its faculty to bring about cellular death, though a recent study by one of us u suggests that quartz has triple independent cytofeio- From these resows Gardner concluded that the soluble silica theory of silicosis had received a further refutation. From the fact that no fibrosis resulted even after 575 days and the low pH of the mixture, it seemed evident that the quartz and potassium carbo nate underwent a more or less permanent logkaf actios, viz., to denavare or predphait comtapatfon. tissue ground substance protein, to attract Gardner did not attribute undue impor and destroy eosinopbile leucocytes, and to tance to the presence of the snail amount attract and cause histiocytes and fibroblasts of ciiafcoai In the mixture in bringing about to proliferate. In the case of the present the Inhibitory action. la vitro tests had al quartz-potassium carbonate mixture the ca pacity to attract eosinophile cells was appar ently also suppressed, as none were found ready shown that carbon does not adsorb colloidal silica, the two -substances having the same electrical charges. in tbe lesions examined. Gardner also detected that the apparent In designing tins experiment Br. Gardner merely bad in mmd duplicating an industrial hazard which he had under observation at the time, His surprise at the result was candidly expressed in some of the cor respondence on file at the Laboratory. It became immediately apparent to Gardner that the results oi the experiment challenged very fundamentally the solubility theory of silicosis and that it possibly favored bis own colloidal silica pathogenic concept. To test out these hypotheses, Gardner pro ceeded as follows f: A 10% mixture of the various components was suspended in iso tonic saline, amoldized, and then stored in protection against the action of quartz ex erted by the potassium carbonate appeared to be more complete than that produced by aluminum in at least one respect. "In the case of aluminum inhibition, for reasons as yet unexplained, quartz that is transported outside the primary organ of localization seems to leave its inhibitor behind and is free to produce silicosis in the metastatic foci." In the case of the potassium carbonatequartz mixture, no fibrosis of any conse quence developed in either the hjngs or the roof nodes. However, in one instance (Guinea Pig 20. Table 1) metastatic foci of reaction appeared under the capsule oi the liver and spleen. They were remarkably like tubercu f Gardner. L, U.; Private correspondence, Sw losis in their histological features but were nac Laboratory Archives, 1W$. obviously caused by the dust. Their occur- 132 k *\ ANTAGONISTIC ACTION OF QUARTZ AND POTASSIUM CARBONATE fence reminds one of the hepatic and splenic dissemination described by Ritierhoff * in an sbrasive-soap-manuiacturing employee. The results of this experiment shed no further conclusive light on silicotic Sbrogeneris is terms of either the surface adsorp tion theory or the silicic acid polymer con cept sponsored by Holt and Yates.1* How ever, the persisting low pH obtained in vitro in spite of the admixture of the alka line potassium carbonate does not negate the possibilities in favor of the polymer theory. The lack of cellular necrosis revealed by this study may, more than perhaps any other factor, account for the rapid spread and aberrant character of the silicotic reaction in victims of abrasive-soap industrial exposures. If the macrophages laden with quartz and the soda ash in these cases fail to die before being transported to far-distant points, an opportunity is left for subsequent extensive silicotic fibrosis once the chemical factor Mocking the biotoxic capacity of the quartz is overcome. SUMMARY the problem of the diffuse, sclerosing reaction and the high fatality rate in per sons excessively exposed to quartz Hour mixed with alkalies is reviewed. Ad intratracheal and intraperitones! injec tion experiment with a mixture of quart2 dust and potassium carbonate in a 3 to 2 ratio is described. The potassium carbonate effectively in hibited the necrotizing and fibrogcnic prop erties of the quartz. This result is apparently not brought about by increased solubility of the.SiO* which is promoted by the K*CO*. REFERENCES 1. Koch, W.; fiber akwe Silicose. KJm. Wchnsehr. *1790, 1930. 2. MacDonald, G.; Plggot, A. P.,*nd Gilder. F. W.: Two Cases of Acute Silicosis, with a Sug gested Theory of Causation, Lancet 2?$46-$4S,1930, 3. Gtese, W.: QtsarsBid>, Scfcwietcntunge end Lungentuberkulose, Veroffenth Kmgv u, Konstlt. Path Jen* 18:66, 1931. 4. Chapman, . M.: Acute Silkosis, J. A. M. A. 88:1439-2441, 1932. 5. Kilgore, E. S,: Pneumcmoconiosis: An Un usually Aevte Form, J. A. M. A, Mi 1414-1416, 1932. 6. Gerlach, W., and Gander. G,: Ober akute Staublimgen: ZugJckh do Betrag tor Frage Staubliotge und Lungentuberkulose, Arch. Gewerbepaih. u. gewerbehyg. 8:44-57, 1932. 7. Gomhardt, G.: Cber die Genese der pneurookoototiseben Lungesindurationen, Arch. Gewerbepaih. s, Rewerbehyg. 4:280-309, 1933, 8. Middleton, E. Li ledastrial Pulmonary Dis ease Due te the Inhalation of Dost, with Special Reference to Silicosis, lancet 2:59-64, 1936. 9. Ritterhoff, R. ).: Acote Silicosis Occurring in Employees of Abrasive Soap Powder Industries, Am Rev. Teberc 43:117-131, 1941. 10. Rossuig, P.: Ober aktzte Silikoseni Zogleich ein Bestrag cur Frage der Sitikogenen Wirkung von StaobgeniKhm. DeLtsehe gesaodhwtfi, 2:317-320, 1947. 11. Zaneui, E.: Ricercbc sulla silicosi is una Cabbrka di sapool abrastvi, Med, lavoro 41:1-9, 1950. 12. Kettle, E- H.: Interstitial Reactions Censed by Various Dusts and Thdr Influence on Tuber culous Infections, j. Path. & Baet. 83:395-465. 1932. 13. Lochtkemper,. j, and Teleky, L.: Stodien uber Stauhfunge, Arch. Gewerbepatb. u. gewerbehyg 8:600-761, 1932. 14. Sehepers, G. W. H,: Cytobtological Mani festations of the Surface Properties of Quartz, A. M. A. Arch. Indus!. Health, to be published. 15. Holt, P. Fu and Yates, D. M.: Studies on the Nature of Silicosis: Polymerization of Silicic Arid Sol* in Vivo, Brit, J, Exper. Path. 35:52-59, 1954. xperimentaiSluchf ofthe tZu-effletal on cJtingJ cfa of ANTHONY 8, OfLAHANT, Sqmmk Uk**. U. Y. down the trachea to its bifurcation. The <jjw -,f|g.n-gia/^11 yj suspended dust was then slowly injected into the lungs. The average weight of the animals Jn this paper the results of a secies of ex used was approximately 600 gm< The dosage periments which I conducted under the direc and the number of injections varied with the tion of the late Leroy U. Gardner, M.D., dust employed. The injections were usually during 1943 will be reported. "Die report wiO administered in three equal doses at weekly be limited to a review of the method and the intervals. The toxic reaction that was mani macroscopkally observable results. The anal fest between injections usually gave indica yses of the histopathologicaJ.reactions are re tion as to the size of the dose that should be ported separately.* used. Certain disadvantages attended this In all, six metallic substances were studied. method but did not outweigh the advantages. These comprise tantalum oxide, tungsten, Dosages were, for instance, controlled to tungsten carbide and carbon, cobalt, cohatdc some degree and doubtless with greater pre oxide, and tungsten carbide and cobalt. As cision than would have been obtainable with will be apparent, these are all substances inhalation techniques. However, there was In which may gesture as potential environ a lew coses come loss of injected material mental respiratory hazards in the cemented through subsequent coughing. There was also tungsten carbide industry. The purpose of in some instances a tendency to produce local the study as designed by Dr. Gardner was ized accumulation of dust, so thaX even dis to establish which particulate metallic com persion of the material was not accomplished ponent, that may be inhaled m sued: an in as certainly as would have been expected had dustry, could provoke pulmonary lesions, the substance been introduced by means of TECHNIQUE the inhdmkm technique. Some hazards also attended this technique. As go genera1, anes Dust was introduced into the lungs of the thesia was used, it was not always possible guinea pigs by the intratracheal route. This to control struggling movements of the ex technique in our hands was performed with out general anesthesia, instead, a 5% solu tion of procaine hydrochloride (Novocaine) was applied locally by swab to the mucous membrsnes of the animal's throat. A nasal speculum, modified so tlrat it might be used as a nwinh gag, exposed the vocal cords to view. A special 20 gauge, 6 in. needle was passed between the cords and gently inserted perimental animal. Rupture of the lung, with subsequent injection and even death, there fore, sometimes ensued. Of one thing one was always certain, however, namely, that the dust was effectively introduced into the lungs by this method. fcfSUtTS In the case of tantalum oxide, tungsten, cobaltic oxide, and a mixture of tungsten Recorded for publication June 28, S$55. as a mouth gagf exposed the vocal cords to Research Associate, The Saranac Laboratory, view. A special 20 gauge, 6 ir>. needle was * References i to 6. going technique. Unless the product was sup- 114 EFFBCTS OF RARE MBTA3S ON ANIMAL LUNGS pUed in. a sufficiently fine state of subdivision, attempts were made to obtain 3* and under sup by sedimentation in 95%, alcohol- In soipe instances this did not prove possible, and the dusts were introduced as received. The dusts were suspended in isotonic saline is 30% suspension and sterilized by arooidizatn.(lO0 C) for one hour. The dosage in eat* case was ISO mg. administered in three equal quantities at weekly intervals. $ix guinea pigs were used in the study'of each dust. An occasional animal died of ioter- Ta$ul' EJJVfti of TaniaUn Oxide Table 3.- -Puimcmary Egecu of CobgUic Oride ZnfrStracberi WhxJ OaioM PI*. *r Dajl After Last SO ts o Dfed nt met E J> as its as uo X X u see X Gross Puioaoeary Apcar&aeB L*m W*k 4i0e term ***** ot ylJEDfAUtfi* PtwwbobKC- IU) atJabtly 8rm, diffuse, or lawtutf &nt mu fil*riy rvwt dnuasertbetJ lacfeo* BUsbO* ana dmnsHfoetf Mm tfOs vt*ti *toMtaetoo Pew Urge ctrevnj*tr%xd a-d <TfT) an*U rod ot dcat atpmUQM: II are eon k*-;. - x. Zotratracbeah Method . " pleura. No appreciable temporal change in rite ' gross,character of the lesions was noted in Gatort"..**?;< DMtf T*n Hj, or ox>n euhwoaij _//>-. femtea ' V"`L`n^vvv' <-OifdeioajnteaHtmaowoMulimVia'n'.vHia -Av. these successively killed animals. On the whole, therefore, these four dusts proved to be friabvtly benignjh their biological cfiects sLW,.` .** ft Tfi5l* Wftqff. on _,,ue. tr~: -tfS'L ijsree artfle ctwwv7**J * *- * * *' et ie*iB.twjr . ;.. -- '* fim . Urw, :*.v .. Jjne M( mu ctreniv t ?*-. v . "* -ntuf tfuat VsSouMnr*^. comet pacBuKKiliU B Ko (hitt re*M)oa dt*. current infection, and the remaining animals were killed at 1,4,8, and 12 months after the last injection. At autopsy (Tables I to 4) the kings usually exhibited large circumscribed, soft 10 slightly firm, pigmented lesions. Oc casional email discrete foci of pigmentation were widely distributed beneath the visceral . Table 2 ~-Pn!nt pnary Egecu of Tuitfisfen * * * ` ' 1 ''Metal Dust ZflKatraeheal Melfwd metal, attempts to obtafn_3jt andunder product by sedimenta tion in 95%` alcohol fasted. The dust was, therefore, used as received. The particle size Table t.--Pvlwnary Efetlt of T*t'*ssleit Carbide and Carbao ZsitratractauS Mrlhc-S--Turjgyi Carbide: Carbos Ratio--W: 6 OetacB Car* Al(f *. Lett Xo. IMttCfctt DM or med X a& & t*o B K ............. . Groei rvlnteoerr Reet^Wtr UoderBtrtr hrerr Mart &JfTTK6ia(loe ot dIHute w(t iorelted ertea ljirte ettas ot aoit black triSincBtaliefi UofelttJ dJffuM area* ot oft Wart btaaeota. em ts too si m E 1 Disuse areas of eott K 1 tiiisk oust oWwesie* X f tios Gnle* D#r After 'DM . Pir, Left or Kb. toSeettoQ sme* ?. E am X a ua a* m M a a SO) t X a s KrnUos Cert fref. ellrhia 8TM pfpneD(1loQ <w \*n>* *sft rrtt>~f focuj dost Ke'tioD Ve S's W WttoB pmDl Xo eroeti dust IttioB pmeec 6^eH aas of cufffertee: 00 OlfTOtBUJfcOU Smell er<8 o( porXtrla*; bo pismfOfatioB range was as follows: panicles 5* and under, 95%; particles 5^ to lfy*, 5%, A few granules measuring up to 30) were also present. The dust was gradually suspended in isotonic saline by means of a rubber policeman and diluted to 10% suspension. Sterilization was effected by amoldization (100 C) for one hour. One dose of 50 mg. and another of 25 mg. were given, respectively, to each of two ns TxftLs Effects of Cobalt MetaJ Bust Xnuatnicfwal Method DELAHANT GtMBtt Ft*. Ko, to ts a IB ft ft *7 sa <> *> u Ooutstr' , of pu K\ to 3 to 2 to J Vi I tfi 2 at I at I St a Si i a 86 i e 30 8 <7 8 4ft 20 t 44 w 8 $ ao 8 U it 8 XSjactloo 2 1 1 uo Kb Bfedot Elite! Q D & too E 80 8P 8& IS J> 9*0 X V % 4 & l 6 Df Dj il D ISO Oro* Pvbnofixy a*MUoa GtatTftttf ra-egaeuri Acute poounualtw Aeutt fuia<uJt* Ko <5<flail* <nm pjeaceuuoa few pkurti *0i**rej* b&siII Bno efrtuswcnb&a cuai IttlUOt Oblii/iauTM ptemtle Acau pwuiaoflitij poI*eUe>tBtcma*ci2*a Mu* hsi K dK*t *um> pempetok Fl*w!r?*! JaaftmbesjJo*sui;iaowneMn4o4e- SWA a4 arvri ns*Q foci 01 dtut FifTBMSlaHOIS AtuU pDUMaJUa AUK ud cfttoalt povwB*ttUs Ko rro*s Raotiofi series of six guinea pigs. Two doses of 5 mg. each were injected a week apart into a third scries of six gomes pigs. AD animals (Table 5) became acutely ill within 24 hours aiter injection regardless of dosage. Of the first series, which received the SO mg. dose, three died within 48 hours. Of the three survivors, one was hilled eight months aad the reisaisuog two one year after the introduction of the cobalt. Of the second series, which had received the 25 mg. dose, three also died within 48 hours; one died after 19 days. Hie two sur vivors were killed, respectively, eight months and one year after the introduction of the cobalt dust. passed through the initial phase, such as pleura) adhesions and sometimes obliterative pkuritis. Black pleura) dust pigmentation was often visible in the unobscured portion. The tungsten carbide and cobalt metal dust, which was present in a ratio of 9l*.9, was studied by means of both the intra tracheal and the inhalation techniques. As received, the dust required very littk prepara tion to reduce it to a siie of 3>4 and less. Sedimentation in 95% akohol for five min utes was sufficient. The identical intratracheal technique used in the preceding experiments was applied, but three equal doses were ad ministered at weekly intervals, resulting in a total dosage of 150 mg. In the third series, which received two doses oi 5 mg. each, all survived the initial dose, but after the second dose five animals died, between the 4th and 11th days. The lone survivor was killed at one year. All ani mals dying within a few days after injection exhibited an acute pneumonitis, usually ex tensive. Of the acimals surviving tins acute initial reaction, those kilted at 8 and 12 months presented gross evidence of having There were no intercurrent deaths (Table 6), and i!\c six guinea pigs were killed as planned at 1-, 4-, 8-, and S2-mmnh intervals after the last injection. Mactoscopic&Hy, the lungs exhibited well-circumscribed linear wi diffuse patterns of black pigmentation. All lungs were normally soft, and no appreciable successive change in the character of the lesions was discernible by naked eye during the 12-owtth period under studv. 116 EFFECTS . -x. ' OP RARE METALS ON ANIMAL UJNGS f* i %'* f-V*'5**" /. particles .per. cubic foot of air,' or approxi- TW,, C.rW, Mrif ta maWy 8,800 to 10,600 particles pJ cubic h*rt*ntbcal Uetbod--Tun^ws CwUdt ; Coteft Ratio--W# centimeter. The parades were O.Sft to 2.0p. in size. During the second exposure, of 15 Dm Oe^m* tsr DM or [* to. nowues tn^ * Otoca PaimBiT -s aa<uoe v??'S W .. i.' 14 m a . L*>nvt ooo{ l4tot9imf wtmnttteJoneM K 1 Soft lealooi of botb Snaar UKl iliffUM 403t plX' BwatoUoB ** u ' ho K c&*S tett foot o< UaS MtBMUOoo r *' .*'uS' < * ' E . 1 Sell led oi bUck W. X i bscbuuoo .*ic.e^ K. J days, the concentrations were appreciably re duced, to approximately G,OQO,OCO particles peccubicfoot of ait, i.e., approximate^ 2CO particles per cubic centimeter. Twenty guinea pigs were exposed to this dust by inhalation eight hours daily for five and one-half days a week. After approxi mately 20 days (Table 7), five of the animals had.gwd, and dust exposure was discontinued feemhafation experiment, the nuxtii* **!s20th <*7- Threemore annuals d*d on ised *as ^uitc different. On the ba% of ^ bowing two days. As the condition of k-ray diffraction-tine, intensity, rE V^5sbi--' animal, improved rapidly cessation ojr the.Jy'st dust exposure dust by i&haiation in a smaU dust box/ meas uring 4 by 2 by 2 ft. This box was equipped with an atomizer for dispensing dust in a dry form. The concentrations were somewhat irregular. During the first 20 days of ex* pcsure, moderately high concentrations were untajnod,J..e., .250,000,000 to 300,000,000 pred&bty lower concentrations. After 10 days of this second exposure, three more animals had died and a further two died on the 13th day. After 15 days, this second, the final, ex posure was, therefore, terminated. Two aaimaJs died, however, one day later. The re maining four animals were killed as follows: ..Tasle '7j~-Pu!mcnary EgteU Satejaiga CttrbvU and Cetvtt M*iat Ratio--3?l 1. . D*rta ,V 1 Dor** ' .ftj.V *; tTja -. jBxpotart' -*Afrermair , Zzpofor <; S--roate*d*.., . SonnslAtf . EAtvWoo*r>a t* *** PeHF PtAoC If-. rJ> '* 6:K:v; 'P. a - / .u. w. ;*r ! so .*r- . i *.* ,< * ** . i, V* . $*1\***?' f * -y.flAe*. -.'*' u it DKM(EMer D D D p r> D D J> E Z> D D Qroc* rnlsMifT Aeblc paasotoBJUf Aceta jwomoaJU* Owe Momb CtK *04 natal*) pDWaVf*1rla ***'& T&r'-' k..v,;?L ?' * ^6 * - *: -6 18 *9 u, a-- a. ^ ' * 'a"?> * 2* i. s in ,, . 1 d/ .. * , \ ' x('J 'v-'w ' 4utc pomnwDiti* ud ibi <teit pir=*"J>Uao \ Plot dJffiua Sait MrsMAUtloB bett pIm*Uod: eeneaMiii*; plant ffftiWeo BcpmlconnaSeitae*S! tt.aSitebu, rebbetT- talntlr 11? DUAHAti? two at 281 days and two at 585 days after termination of the dust exposure. AJi the animals which had died from natu ral causes showed smite pneu/nomfic pulmonaiy' consolidation. Those guinea pigs which survived and were killed at 6 and 19 months, respectively, showed faint diffuse dust pigmentation. Two of the components proved to be toxie (cobalt, tungsten carbide and cobalt). These experiments were conceived and planned' by the late Leroy U. Gardner, M.D. My thanks are due also to G. W. H_ Sthepws, M.5>, S>,$e., Director of The Saranac Laboratory, who sug gested the writing of this report and helped with Its preparation REFERENCES COMMENT 1. Sehepers, G. W. H.: The Bidogkai Action Judging by the roomhty rotes and the nature of the gross pulmonary reactions, it is evident from this study that tantalum oxide, paniculate tungsten metal, cobaitie oxide, and tungsten carbide and carbon are relatively inert when introduced intratrachcatfy into guinea pigs. Cobalt metal, on the other hand, proved intensely irritating to pul monary tissue, and when cobalt was combined with tungsten carbide, the toxic property of the cobaitie component predominated, of Tantalum Oxide: Studies on Experimental Pul monary Histopathology, A. ML A. Arch, indusl liUh Vt'.UlAT*. 1SSS. 2. Schepers. G. W. H: The Biological Action of Particular Tungsten Metal : Studies on Experi mental Pulmonary Histopathology, A. M. A. Arch. lkw. Heahh ttsUt-US, 1955. 3. Schepers, G, W. H,: The Biological Action of Tungsten Carbide and Carbon; Studies on Experimental Pulmonary Hislopatboiogr, A- U. A. Arcix lodust Health t&:137-139, 19S5. 4. Schepers. G, W. H.: The Biologies) Actios SUWMANY oJ Particulate Cobalt Metal: Studies on Experi mental Pulmonary Histopathology, A. M, A- Arch Experiments ate described in which six Indus*. Health IS;127-233, JSS5. metallic substances, to which personnel may 5. Schepers, G, W> If.: The Biological Action be exposed in the cemented tungsten carbide industry, were introduced infratracheally in guinea pigs. Tour of these eompouer^ts proved to be relatively inert (tantalum oxide, tungsten, tusgtten carbide and carbon, cobaltic oxide). of Cobaitie Oxide: Studies on Experimental Pul monary Histopathokffy, A. M. A. Arch. Indus*. Health IS*124-126, 2955. 6. Schepers. G, W. H,: The Biological Action of Tungsten Carbide and Cobalt: Studies ob Experimental pulmonary K&opathology, A. M. A Arch. IndusL Health WsMD-246,1955, Olte ddioio^icai^dction oj? 1\fantaium Oxide Shrfia m E*pericaeffts* PatBMaty Htepar&ot97 have engalfed the metallic particles, but most 0. W. H. SCHENKS, M.0V Die, Swoaae Let*. N. Y. of the dust lay free in the alveoli. There was a tendency toward subpkural or cortical localization of the pigment and of the cellular The method followed in this study has been described by Delahant,* and the present account will be limited to a description of the microscopic changes associated with reten tion of the 3 ft and smaller tantalum oxide dust partides in the lung tissues a those guinea pigs which did not succumb to intercurrent infection. Wltether the death of the latter group of animals was related to the introduction of the foreign agent into the lung tissue could not be excluded with certainty, but the over-all benignity of the reaches) rather suggests that the pneumonic infection was purely coincidental. reaction (F;g. 1), A minimal degree of vesicular atrophic emphysema and perivascular deposits of dust-filled macropliages occurred {Fig. 1C). TJte blood vessels generally were found to be markedly distended, and the alveolar capillaries were engorged. The lymphatic system seemed to escape almost entirely, but more generally there was some central pig ment deposition and hyperemia in the hilar nodes. From this type of minor response, reac tions varied through all nuances of severity to a marked type of peripigniemal interstitial cellular prueumomds, with associated sanguin acute response Within one month, the intratracheal intro duction of the 10# suspension of tantalum oxide dust (ICO mg.) produced focal reac tions ^rhose,severity apparently was quan titatively, related, to topographic dispo- sitiorfxjf th*;metallicToxide. .An almost uni versal rmnorXtssue, response was also disceraible^- t* The-, hast.jrtengc observed.rcomprised an acute to sufoepte t>ronehitis and bronchlq- Vstis'jn^nUesu^g hscirgnmarinas epithelial pK^fferatfon^rtd desquamation, mucosal hj* petsfoj^,;W^a/peribronchitis M$. eous alveolar exudate in some areas. Copi ous pigment collections were found trapped among the proliferated cells, which consisted for the greater part of endothelioid and plasma cells. Over relatively large areas the alveolar .walls were therefore markedly thickened (Fig. 1Z>). . In isolated' areas, the concentration of pigment wa^exceedingly dense, and there was some attempt at encapsulation and organizatioo_Qf such deposits. Only in rites auth as these was any cohagen found. y These we^tf^changes which were to be sb. wr&a.month after direct exposure Pagmest ^gr^Baies could be traced to tht opulmonary tissue*to the metallic oxide. adventitial layers of thfi bronchi where plas- RESIDUAL LESIONS toacell reaction to these granules was pres1-- "Vht at some sites. _T . / ' A year Jater the whole picture had . In the iung.parenchyma, }be minimal reac dianged, and there was almost complete re covery of the *cme process, though residus! tion was found tb fdesist of alveolar cpir f /. thehat prelKeration.'Wth macrophage- caj-; 4X tawh.. Sonre^^sthese1 cells were seen ti sequelae persisted. At some sites some very minimal cellular reaction persisted, mostly Is ' J `"B1.V *Rcord^. for {M>Kcat*6ii June V, S. 'JpSS. > ' ip,relation to the Yesidual presence of macro ' phages' containing phagocytosed metallic Director The Sraa LabffraWy. ; - particles. Tb? msjn cell types were plasma 319 SCHBP&RS F, \r~Pulosooar? yeaetiea to tantalum oxiie--gtriroa pig hag: om month. A, bronchitis *ro epithelial dtsquamadon and peribronchial cellular accarrofsticm. B, stibpleural ptgirKJiQiion and iutuseiual pneumonitis. C, perivaicttiar cellular acaraaUiicst acd pigmentation. D interstitial pneumonitis around trapped pigment in atelectatic alveoli. ceils, eorinophiles, and proliferated alveolar epithelial cells. No fibrocytes were seen* Isolated small pleural plaques were dis covered (Fig-. 2A). These comprised focal accumulations oi proliferated mesofhelial cells with centrally trapped metallic particles. The bronchi and bronchioles appeared to have undergone almost complete healing, hut there was slight hyperplasia of the epithe lium, even though the ciliated surface had been restored (Fig. ZB), lymph nodes. No reaction was discernible around it (Fig. 2D). COMMENT The pulmonary reaction to tantalum oxide dust introduced as a 10^ suspension was found to be essentially benign, involving transient bronchitis, interstitial pneumonitis, and associated hyperemia. Residual sequelae of any consequence comprised focal hyper trophic emphysema and organizing pneu Periiaps in consequence of earlier sustained bronchial or bronehiolar damage, foci of hypertrophic emphysema were found (Fig. 2C), a feature which was superimposed upon the atrophic emphysema already apparent within a month. Most of the pigment had been removed from the lung tissue by the end of the first year, and some of it could be found in the monitis around excessive metallic deposits. The fact that there was so little residual effect after a year does not yet warrant classification of this dust as innocuous. If should be emphasized that the result of re peated introduction o! the substance by inlialation may well prove to be considerably more pathogenic than would at first seem probable on the basis of the lack of a J20 BIOLOGICAL ACTION OF TANTALUM OXIDE Fig*. 2--Pulmonary reaction to tantalum oxide--quinta pig lung: one year, A, epipfettral ] - .fibrocelfeUr pUquc around collection of pigment B, bronchial mocoa showing minimal residual i - .. * ..submucosal and adventitial cellular mfiltrstion &nd. mioimal haul cell epithelial hyperplasia. \ . v'. ; CrfoaPb^enrc^tu*em^ysema due to ovewUstemwft of alveolar ducts. D, pigment acranmb- I tlec aj'tbe cortex of a hilar lymph node without any significant cytologies! response around it. -*nsme'fibgkje, respons'e. *Tnh.e m.inor .Vb"ron- i\ h)$e<l>!asia dienes further. SUMMARY oxide when introduced into the l* ? fftitneg pi lung by the intratracheal technique S1^nt` 85 &UCh: produces' transient bronchitis, interstitial ^ ,cnfcno]mf fgynd in association ,r, -n.yr- *;* :*~*-- . .. pneumonitis, and hyperemia with residual f. -3^>0nary ons> ,-V focal hypertrophic emphysema and organ- -- ' - ^^^re on^|;.5Ub}tct :of tantalum ^ ^QnkU around dqx>sits. 5,1"i'-- Th^stXi.-nor.fibrcgenic. dust is fftjj? .;.V . * ^ "^"bly becausejnnnan ex** * * 1 REFERENCES >0* Indirect.' .'I, Detent, A. B.: An Experimental Study of "ft?*" 4?'.mad* '? tenulum by Miller. tKj Elm ol Rare Meal* m Anieal Luf.es, i; ,-V*' . *^y. and -b^^GerWrty, i, Wyatt* and seems likely by S]-. A. M. A. Arch. Indust. Health *2:116-120, 1955. ,bat m " Z'iMiHer. C W.; Davis. M. W.; Goldman. A.. tantalum oxide may be andWya4.P.:Pneumonio5tSin,heTUngSt<n- : . po^ulanj. .Ca'tbWf.'Tpol Industry, A. M. A. Arch. Must. there win still be for some time to come othsr Hyg. *;45}-465, 195S, associated environmental hazards of more 3, SJoberg, S, G.: NieialWammpi^umooitef. material consequence. Nord. ttwI. :ll7*tJ9. 1950. m 3L &oL ogica foodies m ExjMKftentel Mmoioty Niih^Q&efosy of columns of lymphocytes into the abutting alveolar wails. Eosinopbile cells may be $. W. H. SCHEPW5, Mi>v D^c, Sfl'woe Le*, H. Y. s intermixed with these lymphocytes. "Hie hilar As described by Defahant,1 the cubaltic nodes show diffuse hyperplasia but only oxide <k&st was introduced in three weekly seamy pigmentation. doses of 50 mg, as a lOffc solution. Observa- tioos were made at 1-, 4-, 8-, and 12-mcmh eaaemic sespoksk intervals after the fast injection. Twelve months after the introduction of - :* ACUTE SSACTJON ' The effective introduction of this metallic oxide into the guinea pig Imig provokes the cobalt* oxide into the lung, the forego* fng changes have been largely reversed. Oxide particles may still be aggregated to* gether into focal intra-alveolar accumula V.: within a nwptli a.tsubacuh* peribrdndwal i i ceJIufef pcqltftntioe}&s}3 focal pneumpjjijis which'is confine#40 .the* area of.pigrfient tions, but now they are entirely contained within clusters of large kooiaphores (Fig. 2<4). There is now but insignificant residual deposition.; Ooasibnal bronchioles ..sltpw tissue reaction to the presenceof these foreign ( epithelial damage, but forelie most j substances and .no eosinophilia, Nonpig- the only change consists of mucosa! plasma mented macrophages are scarce, and there cell and cosinophile infiltration. ' The parenchymal foci of teactson vary in character in accordance with * the amount = * of 4u deposited^ In idtne stress, the cellular reaction is disproportionatfi^tb ^The amount ; of*63st present^Fig. 1^). in others, the < cpbaltic oxk)c}prficles ^relmassed together, v - At*cb site$'F, IB); by far the greater are no giant multinucleated cells. At isolated sites, typical dusters of hyperinflated alveoli occur. This type of hypertrophic emphysema appears lo he the only significant residual lesson provoked by die cobaltic oxide. The bronchial epithelium and mucosa are restored to almost complete normality, but slight adventitial cellular accumulations persist ' ' proportion of?)/he$c Oxide particles are as ' yet 'extracellular Rarelyvan -alveolar mac* *rop6age may be observed to be in the process of engulfing such granules, and many parti* ; debate clearly lodged .jiwthin the thickened - y alv^>1ar walIs,,,Thc dominant ^elf types ap\ ' pear Jo be plaima cefis. amf-macrophages ' srifh; occasionar .eosinoj^iles.' 1fhe' alveolar walls.are.relatively broadened near the focal dust deposits but are guite normal elsewhere. . - - Conspicuous pcfivasculSr cellular cuffs suf` round tl smaller arterioles. The pulmceary lymphoid tissue has under gone regional hyperplasia, with the extension (Fig. ZB). The lymphoid tissue, though still abundant, Has reverted once more to circumscribed spherical nodes. The hilar nodes show gbund* ant central pigment accumulations but no fibrosis or endothelial hyperplasia, COMMENT The essential pohti established by this study is that cobalt has an effect on animal tissue when introduced into long tissue as a metal totally different from its effect when introduced as an oxvdc. Harding* has empliasized the relatively toxic effect of cobalt metal when introduced into animal lungs Recorded for publication .June 28, 19S5 Director, Tbe Satssac laboratory, and has recorded symptoms and x-ray signs in men industrially exposed to cobalt pow- 122 BIOLOGICAL ACTION OP COBALT1C OXIDE :Sa"-1 reSSc?*^***' stS T4 p.w &Vtig? < fi && \ rxv Lamnirm, *iiimhiii i t;, \ ;Fg,;j^4Raction cf pulmonary rk to cobattk oxide--guinea pig fang: otte-monlh remit d; focus alveolar wall cellular proliferation tod macrophage catarrh, with minima!*pigment jkfmUixv 8, muasnai focal piguwnt s^gregatke, *<W ineapierrt jfoagoeytosb and parea'i&ymal reaction. Fig. 2,--Reaction of pulmonary tissue to oahaJdc oxide--guinea jug fang: one-year result A, residua! focal metallic retention in pulmonary alveoli, without any associated alveolar wall reaction. B. bronchial wail, showing mild persistent epithelial lypapiau and adventitial round* cel! infiltrtticffL Srtf 5 SB? 8$ cSm rf,-!, *s <*VSf\-,'"T, ; '_ ' '< i.* wt*t 223 SCHBPBRS der. He has' referred to the {act that,, while , SUKHASy cobalt has a low solubility m isotonic saline, its solubility in piastna is 500 {imes greater, Faiihail, Castbeg, Carroxzo^and Brinton* and FairhaU, Keenan, sod Brmtoo* have been unable to confirm ti asarked toxicity of either cobalt metal or the oxide, although they acknowledge the occurrence of upper respiratory tract symptoms ia persons ex Intratracheal introduction of 150 mg. of cobaltic oxide produces a focal and peri bronchial, transient, subacute, inflammatory reaction which becomes virtually completely. reversed vritfun one year. On this evidence, cobaltk oxide may be classified ** a doubt fully toxic respiratory hazard. posed to these substances. It is possible that cobalt metal may prove the snore toxic sub REFERENCES stance because of the cobaltous forts whkh may be released when it comes into contact 1. Debh&nt, A. B : An Experiment Study of the Effects of Rare Metals qq A&u&al Lungs, A, W. A. Arch. Health U;U6-)20, }*5$. with body fluids, whereas cobaltk oxide is likely after uitroductioii into the body to lead to the formatrort .of hydroxyl groups. 2. Harding, H. E; Motes on the Toxicology of Cobait Metal, Brit. }. fndust Med, 1:76-7$, 1950 This subject needs further study in view of the increasing use of cotelt as an indus X Psirhall, L, T.j Castberg. H, T.; Canozzo. N, J, and Brioton, K. P,: Industrial H^gte&t Assets of the Cemated Tungsten Carbide To* trial bonding agent and^with^rticular. rcf**' 4usyt Occup. UtA. *:39}-37*, 3947. owe to the Sdhnceberg problem in ebaneoA FalrbaU, l- T.; Keenan, R. <?, and Bristol tkm with which Wtbes,* among osiers, has H. P.: Cobaft ami the Dost Environment cf the incriminated cobalt as a possibly significant Cesat&ud Tungsten Carbide Industry, Pub. Health factor in the high incidence of lung cancer. Rep, *4:485*490, 1949. Mo evidence in favor of the latter theory S. Weber, F. A.: Die Bergkrankbeat der Err* has been prodstced by the present study on berg^u^e in Schoreberg in Sachsen, Arbdt Rescha- cobaltic oxide. geeoodh. ;J?9*!85. J926, ^Jlte $io$ofyicaH-Action of P,ticU CoUl WletJ on Ewsiraenja! Fshaeasry HittopatfeoSo^y G. W. H. SCHiHtS, M,D,, t>St* Swonec leUr N. Y. The primary purposes of this study were to confirm the acute toxicity of particulate cobalt metal and to determine what chronic lesions ensued in animals which survived the intratracheal introduction of the dust. The latter objective was partially interfered with because of the high initial mortality rate Recorded for publication June 28, 19SS. Director, The Saranac Laboratory. described by Delahant.1 However, sufficient animals survived the total experiment to warrant some observations on the acute as well as the subacute and chronic reactions. For descriptive purpose, a distinction will be drawn between the reactions to the 50 mg., 25 mg., and 10 mg. doses. RESPONSE TO MC, DOSE OF PARTICULATE COBALT METAL The immediate response of the guinea pig lung to tlte intratracheal injection of 50 mg. of cobalt metal particles is the appearance of marked pulmonary edema, with moderate alveolar wall hyperemia (Fig. 1-4). Very Fig. 1.--Acute pulmonary tissue reaction to 50 mg. dose of particulate cobalt facta! prince pig: 24 hours. A, hemorrhagic pulmonary edesoa and capillary hyperemia. B, hilar lymph code showing some hyperemia and edema. SCHEPeKS fo\Se oi the ioreign substance ia to be as an acute reaction; the edema does not seen in the putnvosary partsKhyma, and most occur w the same degree or so uniformly as of it is to be found in the^feronchi and with the 50 mg. dose (Fig. 4A). There is bronchioles surrounded by cells and serum also less hyperemia. Macrophages commence fibrin. The air passages show epithelial to appear in the alveolar spaces and gather desquamation. Hyperemia and edema also up some of the metal particles. Many such affect the hUat lymph nodes (Fig. IB). cells develop conspicuous vacuoles, Eosino The dominant feature of the residual sub phil* cells already tend to make their appearacute response after eight months is a ante at this stage. perivascular diffuse cellular infiltration with Simultaneously, there is considerable bron marked prominence of eosinophil* cells {Fig, chial and feronchtelar catarrh, with extensive 2A), which rrsVc their appearance in large areas of epithelial desquamation (Fig. 4 B) numbers within the pulmonary alveoli, in Foci of hypertrophic emphysema may also dose proximity to veins. Some measure of be present. There is plasma cell infiltration alveolar wall and perivascular infiltration is of the bronchial subnvucosa at such sites and present, and isolated fod of sufcpteural eosirso- some focal hyperemia. phile graouioma formation may be found . Eight months later, healing has proceeded (Ftg. ZB). Regional ofeUimrive bronchio further than was the case with the SO mg. litis, with peribronchiolar fibrosis, and arteri cobalt metal dose and a comparable lapse of olar spasm are present as alarming features time. The residual disturbances comprise a (Figs. 2C and D), Small eosinophil* granu- measure oC proliferation of the lymphoid tomata may also be seen. tissue, especially around smaller Wood ves At 12 months the chronic residua have sels, but with little tendency to extension of taken a <|uite new fecin. In relation to the the reaction into the adjacent alveolar walls. sites of cobalt metal deposition, there now There is also quite considerable eosinophite are areas of quite considerable fibroceilular infiltration, but no tendency to giant cell infiltration. Where dies* lie in juxtaposition formaEton. The bronchial mucosa and epi to bronchi, there may be regions of marked thelium have been fairly successfully and cystic dilatation of epUheiiafced alveolar universally restored to normality and may spaces, and these foci amount to an adeno matosis {Fig. 3/4). Isolated clusters of multi-, nucleated giant cells may occur m relation to massed pigment deposits (Fig. 33). The be somewhat hypertrophic at some points. Lymph nodes show slight central endotheiicnd hyperplasia. bronchial epithelium has partly recovered and is hyperplastic, but foci of chronic in flammatory infiltration of the mucosa may persist (Fig. 3C)> No active pneumonitic area^ were found at fbis stage, but there are foci o! abundant Vomophor* infiltration of alveolar walls. The lymphatic tissue shows no sign of reaction comparable with that m the lung. The hyperemia of the hilar lymph nodes previously noted has receded, and there is now slight diffuse central fibrosis (Fig, 31)). t RESPONSE TO 2$ iSG. DOSK OF PARTICULATE C08ALT METAL * RESPONSE TO 16 arc, DOSE OP PARTICULATE COSAUS METAL When the cobal: is introduced in two suc cessive Joses of 5 mg. each, the acute reaction of the pulmonary tissue is considerably less violent. Once more, however, the immediate response Is an edema which is, however, less diffusely distributed and tends to predomi nate in the peribronchiolar regions. There is markedly less of the tendency to diffuse alveolar wall hyperemia seen with higher concentrations. Within four days much of the exudate has Commenced to disappear, and the alveoli are Salving the concentration of the cobalt now overrun fey multiple dust-laden macro appears to have some influence in reducing phages, with occasional multimsdeated gkmt the degree of pulmonary edema which ensues cells among them (Fig. SA). At isolated BlOLOCiCAL ACTION OF PARTICULATE COBALT METAL F. 4.--Acute pulmonary tissue reaction to 25 mg. dose of particulate cobalt metal-guinea tig: 48 beers A, beswnb*& edema and focal hypertrophic emphysema. B, bronchiolitis with epithelial defamation. Fig. 5.--Acute pulmonary tissue reaerkw fa 2 mg. <to*e d particular ert*l! mul-ytunea pig: to days. A, macrophages mopping up residue of the exudate of the aetfle reactive phase. B, cellular focus with persisting exudate and indpieot orgamsatieo. 129 t t f 5CHEPERS F*r. <S.--Cferaoc putaonary tissue reaakm to 10 mg', to*e of pajIkvUfc eobafr tteeiaf--guinea pig- 12 month*. A, persisting raises ol metafile psitkles within atveoJi without, signifevrt Cs&vx 4kft ateuwS Item. 3. perivasevkr eelhiJar cuff and atrophic emphysema. foci the lymph nodes have proliferated, atvd polymorplwmiclear cells invade the alveoli. Numerous distended capillary loops. may occur within these inflarrunatoiy (od (Fig. 55). The hroochiat symtosa does not slraw any significant signs of injury. Around larger blood vessels there may be considerable fibrose change. The bsonchia! mucosa is restored to normality or may be a little hypertrophic. The pulmonary lymphoid tissue *s once more undisturbed, though per haps a little more abundant than usual. The regional lymph nodes present a meas ure of hyperemia and lymphoid hyperplasia. The lesions initially provoked by the 10 mg. dose ofcobalt metal are no longer demon strable ?n the guinea pig lung by. the end of 12 months. At many sites masses of robaH particles may be found within the alveolar spaces without any obvious tissue reaction in relation to them (Fig. 6A). At isolated points some residual local cellular aggrega tion persists, and in some of these areas occasional multinucleated giant cells may be found. Some perivascular cellular aggrega tions may be seen, and a tendency toward diffuse alveolar membrane fibrosis is present. At various regions some atrophic vesicular emphysema may be observed (Fig, 65). COMMENT The chemical pneumonitis which occurs in response to the introduction ol particulate cobalt metal into the lung tissue of the guinea pig is clearly shown by this brief study to be a function of dosage and possibly due to the release of cobahous ions. The untoward re action to the second intratracheal mjectkm of 5 mg. of cobalt metal particles in animaU which had survived a first dose of 5 mg may have to be explained on an allergic basis, which is perhaps likely in view of the known propensity of cobalt to cause cutaneous sensi tization and conjunctivitis (FairhaJI and associates*). The high predominance of eosinophil* cells in the subacute lesion perhaps signifies a di BIOLOGICAL ACTION OF PARTICVLATF. COBALT Mfr.TAL rct chenvjtropism. The lack of an alveolar wall cellular reaction constitutes a further distinctive feature. The metal is nonfibrogesk and does not provoke a chronic lesion in the regional lymph nodes. Tolerance to the presence of the cobalt metal appears to develop in animals surviving the least dose. This may reflect either a state of biological balance or may be due to stabili sation of the physicochemical behavior of the metal particles after prolonged residence in body fluids. Possibly this cobalt has changed to cobalt oxide, which has already been shown to be inert as a pulmonary irritant (Schepers '). Of all the chronk responses, the incipient adenoma formation appears to he the most spedaoilar, particularly if it is recalled that cobalt metal is an integral component of the atmospheric substances inhaled! by the miners at Schneeberg, long well known as a center of occupational lung cancer production. How ever, there is already much epidemiological doubt concerning the role of cobalt in occu pational pulmonary carcinogenesis, as high neoplasm rates have not been reported from other sites where cobalt is mined, such as Canada (Cobah City), Belgian Congo (Katanga), Norway (Skutcrud), France (AHemont).or Czechoslovakia (Dobschina). Powdered cobalt metal has in recent years been extensively employed as a bonding ma terial m the manufacture of hard cutting tools, and respiratory symptoms and abnormal radiograms have been reported among men exposed to such powder. Harding ' has previ ously experimentally denwnstiated the acute irritant action and hyperemia provoked by cobalt metal powder when introduced as a 5% suspension into the rat and hamster lung or peritoneum. The marked damage to capil laries has been ascribed to the great solubility of the cobalt metal in plasma, which is SCO times higher than its solubility in saline. Cobalt, along with tungsten and ittantum, has recently .been incriminated as a cause of fatal interstitial fibrosis in a Swedish metal worker.* ft is possible, too, that cobalt may have a tissue-specific effect for the Jung. It is known, for instance, that it is not orally unduly toxic, and its beneficial influence on erythropoiesis has been proved in numerous experiments, has been applied in the therapy of human anemia, and has been suspected as a cause of po!y<ytbenria vera in some instances. The outpouring of eosinophile ceils may in a small measure reflect this capacity of cobalt to cause proliferation of the hematon system. SUUMASV Particulate cobalt metal is an acutely irri tating substance when introduced into guinea pig lungs in 50 mg. and in 25 mg. doses. A single 5 mg. dose is not* lethal, but repetition of such a dose proves to be so. Tolerance to cobalt metal may develop after the Initial acute reaction has been over come. The greatest damage caused by the cobalt metal is the obliterative bronchiolitis. A single instance of bronchial adenomatosis resulted from prolonged focal retention of cobalt metal particles. REFERENCES 1. Delahant, A. B.: An Experimental Study of the Effects of Rare Metals on Animal Lungs, A. M. A. Arch, Indust Health 12:126-120, 19S5. 2. Schepers, G, W. H,: The Biological Action of Ceh&lttc Oxide*. Studies on Eapesmemal Pul monary H&opathoJogy, A. M. A. Arch. Indust. Health 12:124-126, X9S5. X Fairhall, L. T.; Cartberg, H, T.; Carrera, N, J., and Bruton, H. P.: Industrial Hygiene Aspects of the Cemented Tungsten Carbide In dustry, Occup. Med. *s371-378, 1947. 4. Harding, H. .: Notes on the Toxicology of Cobalt Metal, Brit. J. Indost. Med. 7:76-76, 19S0. 5, Lundgrea, K. D., and Ohmao, H.; Pneumo* kontose >n dcr HartcnetaH-Tndusfrjc. Arch, path. Anat. 229:259, 1954. 1 I ) 131 pa txptuiPtutof Hutoyetfeekoy G. W. K SCH&m.4A.B,O-Sc, Swsmc UVt,W. Y. Tungsten carbide has atteady received considerable attention as a causative agent of the respiratory symptoms is workers in the cemented tungsten carbide tool industry.* A measure of animal experimentation has ate been conducted on the final product! It does not appear, however, that either the tungsten metal itself or the tungsten mi*ed with carbon prior to the high-frequency vacuum furnace treatment in an atmosphere oi hydrogen, which is needed to produce the eathide, has been studied for its biological action on animal tang tissue, though some information exists coaWTang the pulmonary lesions attributable to tungsten ores, such as wolframite and scheellte.4 This account, am plifying the observation by DeJahant,* may, therefore, serve partially to fill rn this scientific hiatus. The latter are snore usually found near the lung surface (Fig. \A). Where this type of cortical response is most marked, adjacent alveoli are often charged with fine metallic particles; hence it may be presumed that there is a quantitative relation between the regional concentration of particles and the severity of the pneumonitis. Between these fod of mote marked reac tion, the lung parenchyma does not show too severe 3 response, but tltere is a considerable amount of macrophage catarrh into tlie alveoli. Numerous foci of perivascular cellu lar reaction may also be found (Fig, U?). The bronchi and bronchioles show some slight inflammatory change consisting chiefly 0/ mucosal hyperemia. Some bronchioles may also be partly or wholly obliterated through encroachment of adjacent inflamma tory processes. Lymphoid tissue shows no response to the presence of the tungsten in the hmgs, nor do the hilar nodes harbor acy micro*, scopically visible quantities of the particles. ACUTE REACTION TO SfcSTKULVr* TUNGSTEN The eisenfoi and immediate lesion pro voked in the lung through the artratracheal introduction of IS) mg, of tungsten dust in three equal doses consists of an interstitial cellular proliferation in relation to entrapped particles. At most sites the alveolar walls are modtrately thickened, but at isolated foci t> almost solid cellular mass may result. Record*} for publication June 2fi, 1955. Director, The Saraie Laboratory. * References 1 and 2. t References 3 and 4. 152 CMSON3C 2SSSP0NSE TO PARTICULATE TO40ST&* After -the passage of a whole year, one finds that this relatively innocuous seeming lesion has not vanished completely, as was the case with 10% tantalum oxide.* Some unfavorable residua, such as persistent focal interstitial cellular infiltration in relation to retained pigment, may persist. In addition, theft $a now a minor degree o! atrophic vesicular emphysema. At many points resid ual bronchial catarrh may he sn, though most of the bronchi and bronchioles have recovered (Fig. 2A)< Material degrees of BIOLOGICAL ACTION OF TUNGSTEN F& 1<-At* pulmonary reaction to tnngstea--truisea pig hang; one-month resist A, inter* stitiai cdialar reaction most marked around {wall; massed tcogstts pvtkks. B, pemrascuiar cellular aecumubtioo quite disproportionate to the amoi&t erf trapped tungsten. t I SCHEPZRS peribronchial awJ periarterial fibioceiluUf reaction and endarteritis obliterans, with pigment footed witbjfi.' the proliferated jntimal layers (Fig. 2B), are certainty the least inviting features of this terminal response, COMMENT involves the production of focal interstitial pneumonitis and bronchiolitis, 2, While recovery is almost complete after a year, perfotoftrinaS, peribumdnWSar, and perivascular fibrocellular reactions, with bronchiolitis obliterans and atrophic emphy sema, may persist locally. As none of the guinea pigs died as a result of the introduction of the tungsten dust, the substance may be classified as relatively benign. Its toxicity level compares with cobaltic oxide in this respect, but is in sharp contrast to that of cobalt metal4 The industrial significance of this finding might then be that exposures 'to the dust raised in pulverizing tungsten in fbc process ol making tungsten carbide would be rela tively safe, though oot wholly free from risk. On the other hand, the exposures which might be incurred ra handling cobalt metal fines, in the process of bonding tungsten carbide to steel, are likely to be nocuous. Once more h should be cautioned that one may not too freely extrapolate observa tions such as these on the guinea pig to human problems. At most it has perhaps been shown in this type of pilot or range finding study that, while tungrttn dust is not wholly inert, it is relatively so. SUMMA8Y 1. The acute reaction to particulate tung sten when introduced into guinea pig lungs REFERENCES J. Fairhrt, 1- T.; Castberg, H. T; Carrotao, N,` l,-and Brintosi, H, P.x Iwhwtrial Hypent Aspects of the Cemented Tungsten Carbide In dustry, Ocaip Ued, 4-.J71-J7S, W. 2, FatrhaII, L. T.; Keenan, R. G- and Brinton, H. 1C: CobaU and the Dust Environment ol the Cemented Tungsten Carbide Industry, Pub Health Rep. <t4S5-494. \W. 3. Sj^berg, S. G.: Idetafldammpueymooiier, Nwd med. :15?-119. 1950. A. Wilier, C W.j Davis, M. W,; Goldman, A., and Wyatt, J. 7*.: Pneumoconiosis in the Tung sten'Carbide Tool Industry. A. M. A. Arch. IndasL Hyg. 1953. 5. FairhaJI, I-. T.: Inorganic Industrial Ho ards, Physiol. Rev. tSil&202, 394S. 6. Delahant, A. B.: Experimental Study ot the Effects of Rare Metals on Animal Lungs, A. M, A. Arch. Indust. Health, this issue, 9.116. 7. Scbepers, G. W. H.: The Biological Action of Tantalum Oxide; Sto&es. cn Experimental Pul monary Htstopathoio&y, A. M. A. Arch. Indust. Health, this isue, 9*121. 8. Scbepers, G. W. H,: The Biological Action of Particulate Ct&aM Metal: Studies on `Experi mental Pulmonary Hisiopathology, A. M- A. Arch. IrwUsit- Health, ihss issue, p, 127. 134 Stupes os Mittopotfiotafiy a W. H. SCH&W, M.0V PSc, SarooocUfce, R T. While tungsten (nets! has been shown to have a fenced range of bscHogwal effects on guinea pigs,1 the carbide has been incrimi nated as a minor respiratory hazard lor man,** occasionally provoking meta! dust pneumonitis. Experiments on the rat have, however, (ailed to produce either necrotizing or fibrotic pulmonary lesions.* It is possible that the industrial cases may owe their origin to the cohajl which is usually pres ent in industries involving the welding of tungsten carbide alloys to steel. As Delahant * showed, none of the guisvea pigs receiving three successive doses of 50 mg, of tungsten carbide and carbon m a ratio of 94:6 died. The histological features of their lungs are in conformity with this finding. 'the immediate response is a diffuse hyper* emia with bronchial catarrh. By the end of the first month much of the tungsten carbide has been taken up by macrophages, many of which are multinucleated. Most of these cells still lie within the alveoli, but others Iiave penetrated into the alveolar walls (Fig, IA). There is not the same facility in reaching the perivascular JyropJiatjcs seen in the case of tantalum and cobaltk oxide,* but some dust particles are aggregating about Recorded lor publication June 28, 1955, Director, The Saranac Laboratory References 5 and 6. smaller vascular components. Minor areas of interstitial pneumonitis may be found. The lymphoid tissue appears to be con siderably disturbed through the introduction of the tungsten carbide and carbon. There is marked lymphocytic hyperplasia, with infiltration of alveolar walls adjacent to the lymph foci- Some hyperemia also occurs in these areas (Fig. IF). This lymphatic reac tion continues for many months after the acute reaction has subsided. After 12 months there tray be Isolated foci of confiucat interstitial pneumonitis in rela tion to trapped dust masses. Most of the retained tungsten carbide occurs, however, as massed granaka vrithm tdatively atrophic alveoli {Fig. 2A). Many such masses are partially or wholly phagocytesed by multinudeated giant cells. Occasional subplwral granulomata may be found in which a minor degree of fibrocyte formation participates {Fig. 2B). There is no persistent taotK&otttis or peribronchial and perivascular fibrosis, and the over-all impression is that the tungsten carbide and carbon mixture is less harmful to lung tissue than is the tungsten metal. The acute response to the intratracheal introduction of tungsten carbide and carbon is confined to hyperemia and bronchial ca tarrh, minor interstitial pneumonitis, and lymphoid hyperplasia. The chronic residua include trapped dust masses and subpleural fibrocettular gran ts lomata. 13S h>* iH -1 --S,,,' :> SCHSPBR! \/'V V: s*v-^-v>,- -/- 'll fA .s: Fig, J---Acute rewtioo to ftrognea cuVt& asnl eajUvr-^ulms pig long: ooe-roonth result. A, aggregates <rf particles lying wilbin alveolar spaces of panly intwpoTWcd into aiveolar walls. 6, IjttqAioid hyperplasia, with Evasion of alveolar walls adjacent to nodes. Kjj, Z--Cbfonic putao/ury residua associated with fibe wtto&rc&Q o5 tucgstco carbide and easbcsj--guinea pig lung; pfryear result. A, focal arcuflsuJafion of dust muses, most sA wfcjdi are cfttai&ed in past crik B, stfbpleural fibroceJKiiar granuloma. f*' LsV, 'il U.-'? .-s*. ..? 'XI *7 r^O.VeCi:' Gk-V &i 136 r.-..v*.''v. .'^/ v--.- - BIOLOGICAL ACTION OF TUNGSTEN CARBIDE AND CARBON REFERENCES }. Scheffers, G. W. H.: The Stolegical Action of Particulate Tungsten Metal; Studies-on ExperfettaUl P^vecettry HiMopathoiogy, A. M, A. Arch Indus*. Heahh, this issue, p, 154, t Sjoberg, S. G.i UMalfdanunpoeumccDter, NonL med. 41? 117-119, 1950. 3. Miller, C. W.; Davis, M. W.; Goldman, A., and Wyatt, J. P,: Pneumoconiosis in the Tangsten* Carbide Tool Industry, A, M, A. Arch, indust. Hyg. *s4SV4bS, my. 4. Deiahant, A. B.: An Experimental Study,of the Effects of Rare Metals cn Animal Lungs, A. M. A. Arch. Indus*. Health, this issuer p. 1id. 5, Schepers, C, W. H.: The Biological Action of Tantalum Oxide; Studies on Experimental Pul monary BUtopuholcgy, A. M. A. Arch, Indust. Health, this issue, p, 121. Schepers, G. W. H.: The Biological Action of Cobaltic Oxide: Studies on Experimental Pul monary HtstopatittJogy, A, M. A. Arch, IndusL Health, this issue, p, 121 137 Sruitc* on apn0taMf Psfwowj <3. W. K. tzmt*S, M.PV t>Zc*Ut*na< IM, H Y. As has already been explained,* this ocperirnental investigation of the effect of par ticulate tungsten carbide and cobalt metal on the guinea pig iut^ tissue comprises two phases, vis., an intratracheal study of tung sten carbide amj cobalt in the ratio of 91:9 and an inhalation study of the effects,of these suhstanc&sin a ratio of 75:25. In the former study, a known quantity of 15G mg. of the foreign materials was introduced into escI? experimental animal, In the case of the 2 .1 mixture, the tungsten carbide and cobalt dust was inhaled for a total of 25 days, with a rest period alter 20 days, followed by re duction of the dust cloud to about a third of its earlier concentration for the balance' of the period. Unfortunately, there was a high mortality among the animate so that a study of the histological results was partly inter fered with. Sufficient daU are available, however, to present a rcascrt&Wy dear pic ture of the biological effects of these sub stances, INTBATKACH EAt STUDY Tuacsrrs CUabfi> #.* CobjO-t ts 1:1 Jtario The predominating immediate effect on the lung of 150 mg. of a 50:1 mixture of iuugrten carbide and cobalt r to provoke areas of dense fibrosis wherever massive deposits may be estsblislsed. Mora generally there is cellular alveolar wall infiltration to the ex tent of producing almost confluent pnetimomric areas. Some macrophage catarrh, Rererdcd for ptihUeathn June 2$, 3555. Director, The Saranac tabwalory. with scanty particle iogeslion, also occurs at this stage. Generally there are but one or two particle per koniopbore. The perivas cular areas also become infiltrated with lymphocytes, which surround particulate aggregations (Fig. 1A). Vet there is bo tendency toward invoheejnem id tht hilar iymphstks wiflim a month from the time of intratracheal (ejection. The bronchial epithelium and mucosa tend to escape any material damage except where massive accumulations of dust may be de posited, Id such areas there t a tendency to- ward the development of bronchial crypts (Fig. IB). The pigment tends to be incor porated in the bronchial mucosa, and a fairly firm fibrous reaction results around it. The epithelium overlying the deposit seems to be of the normal kind. Where'the dust has gamed access to the pleura, a dense fibrocellular reaction may ensue. Twelve months later focal accumotetions of massed particles .may sail persist ia the alveolar spaces and interstitial planes. Slight cellular and mild fibrous reaction around these deposits may 1* found, frequently with abundant eosmopfcitfa, There may also be residual patches of pneumonitis (Fig. 1C). Many of the brondu show peribronchial fibrosis, and at isolated points there is some papillary hypertrophy of the bronchial mu cosa. Arteries likewise reveal a tendency to ward residual periarterial fibrosis (Fig. \D). At this stage a minimal amount of the particulate matter has been transferred to the hilar lymph nodes, where it is deposited is) the subcapsular or perilymphatic rones rather tian in the nodes themselves. BIOLOGICAL ACTION OF TUNGSTEN CARBIDE AND COBALT Fag' J.--Pulmonary tisjut reactkn to injected tungsten carbide and cobalt--guinea pies: intratracheal Injection : 1$0 mg. dose m a nt*o of 93:9. A, generalized alveolar wall thickening Coca!!; exaggerated with perivascular cellular infiltrate (reaction after one month). B, Coca! accumulation of metafile particles with surrounding fibrosis and bronchial mucosa! crypt forma tion sad bypenraphy (reaction after w* rsvomh), C, deposit of metallic particles with associated cicatrization (reaction after one year). D, paravascular metallic deposit with peri- Jascolar fibrosis (reaction after one year). SCHEP&RS White (he above time reaction basically resembles that already established tor tung sten carbide,* the tendency toward peri vascular focaKzatton fife' reaction and aUg rite stimulating impetus impartedto the bron chial epithelium may be attributes i the coBaltic component of the introduced dust." The explanation for file fibrotie response is not immediately apparent. WHALATIO* STtlQY Toxcsr** Ctuune a*o Cobalt is 75:25 Jbf>o The inhalation oi this 3 .* 1 mixture of tungsten carbide and cobalt metal In high coacee?ration rapidly provokes a diffuse inSammatory reaction but, except for small areas, no true pneumonia. At the cod of three weeks the lung tissue presents a hemor rhagic appearance, both from dilatatios oi alveolar wall capillaries and through escape of erythrocytes into the alveolar spaces *6 many points. Plasma cells, lymphocytes, and polymorphonuclear leucocytes may be found in most alveoli, and a fair number of macro-; phages, the majority containing some in gested particles, are preseat, Al numerous points the alveolar walls are fined by prom inent septal cells. Neither the bronchi (bronchioles) nor the large? Wood vessels' show any- significant deviation (Fig, 2A). these cellular infiltrations are more con spicuous..Dust particle* are abundantly pres ent in the alveola* walls but are always intfactllaiar in tiwr disposition, lying within the pulmonary macrophages (Fig. 2B). Considerable quantities of the foreign ma terial are obviously being transported from the lung to the bite* lymph nodes, for at six weeks a wdi-defined cortical zone of epi thelioid reaction has become established In the latter; It would seem that the prolifera tion of these reticuloendothelial cells Is a specific reaction to the presence of the dual substance,as neither'rise tungsten carbide nor the cobalt itself provokes this effect sep arately (Fig. 2C). On reinstifuting dust inhalation for 15 days, but now at a much reduced concentra tion, a diffuse hyperemia and alveolar edema once more result.* On leaving the guinea pigs in normal air for six months hereafter, in entirely different type of result may be observed. Multiple foci of peribronchial and peribronchiolar parenchymal reaction and an unusual and cxubqratw type of metaplastic bronchial epithelial hyperplasia, with villous papilloma formation, constitute the main teatores of the condition at this stage and com mence as early as six weeks after cessation 1 the exposure (Fig. 2D). On withdrawal of the animals from this obviously intolerable dust environment at the end of three weeks and restoring them to fresh air for several weeks, a considerable degree of recovery from the acute alarming phase of the reaction occurs. At Isolated areas some hyperemia may yet be observed at tlie end of six weeks, but at most rites the capil lary hyperemia has receded almost entirely, and many of the alveolar walls arc inter rupted so that a mild degree of atrophic vesicular emphysema is present. The inflam matory reaction is now limited to a mild al veolar wall cellular Infiltration, consisting primarily of polymorphosvudear leucocytes with occasional mac*ophages. The alveolar septa! cells are also prominent, but there is very little liberation of alveolar phagocytes, though occasional pus cells are presto*, Around the smaller arterioles and venules, The petifcsooclticrlar reaction consists partly oi m interstitial cellular infiltration, many of the component cells being eosinophiles. Tjie alveolar septal cells tend to be promra*.t!y developed, and several may be seen to be undergoing transformation into macrophages. Within the alveoli may be found aggregates of particle-laden macrophages, some poiyThorphonudear leucocytes, plasma cells, and numerous eosinoph/le cells. Occasional mnltinuckated giant cells are to be seen. The alveolar capillaries art not conspicuous (Fig. 3A). The bronchioles show quite a broad zone of plasma cell infiltration of their adventitiae, with occasional pus cells and eosinophiles. The most spectacular change In the bron chioles, however, concerns the epithelium, which is heaped up at numerous points into papillomata consisting of many levers oi 540 BIOLOGICAL ACTION OF TUNGSTEN CARBIDE AND COBALT Fie. 2.---Acme reaction to InhaJccE tungsten carbide and cobalt--guinea pigs: inhalation experiment. A, hemorrhagic pulmonary reaction and alveolar wail hyperemia (reaction at three week*)- B, Soca} parent^ymai reaction, dominantly ictra-alveolar macrophage formation (reaction at si* weeks). C, cortical endothelloid protiferatk of the hilar lymph node (reanion at six weeks)- D, villous mucosal proliferation of a bronchus, with incipient epithelial metaplasia (reaction at three months). - -'~t 141 i < 4 SCHEMERS Fig. 2. experiment f*r 2t fflonth*), fcWPteii* W i" ' "*"* peribronchial fibrocelfuU?Vwc&f'<rc5S5S <*- BIOLOGICAL ACTION OF TUNGSI'EN CABBWB AND COBALT large nucleated epithelial cells containing trally located or disposed along the cortex a minimum of cytoplasm (Fig. 35). Occa and contain a little pigment at their periph sionally such papillomata contain a fibrous ery. The tmrapulmonary lymph nodes have stroma which tends to be infiltrated by plas returned to normality. ma cells and cosinophiks. The Jumina of some of the bronchi and respiratory bron COMMENT chioles are almost completely occluded by these proliferating epithelial cells and papil lae, so that regional focal emphysema may ensue distally to these partial obstructions. At several foci in the lung there arc also small confluent endothelial granulomatous formations with central pus accumulations. The purpose in combining the tungsten carbide and cobalt in the ratios given in tiie foregoing accounts was to mimic for experimental purposes the circumstances in whkh industrial employees may on occasion be exposed to these substances while pre paring mixtures for the purpose of making The lymph nodes within the lung are not alloys, materially affected by the tungsten carbide and cobalt except that there may be some measure of eosinophile infiltration. The If the sequence of events described for the guinea pig bear any relation to the manner in whkh human lung tissue may be expected to hilar lymph nodes continue to show cortical react, it would seem that great caution endothclioid. hyperplasia. The larger blood should be exercised so that the metal fines vessels are unaffected except for some ad are not handled in such a way as to create ventitial cellular infiltrations. an atmospheric contamination of any severity. After elapse of another 15 months, i. e,, a total of 21 months from the onset of the experiment, the residual effects of the brief exposure to the tungsten carbide and cobalt As was show*, the reaction to the dust mixture is appreciably less violent where the cobalt component is of the order of 9%. On the other hand, the more pronounced meta! may be assessed. tissue response, and particularly the prolif In the trachea and bronchi, the epithelial erative and metaplastk epithelial changes, hyperplasia and metaplasia still persist and may reflect a sensitising propensity for which show extensive superficial ulceration, with cobalt is already well known/ though it had cellular desquamation, so that the markedly not previously been shown that cobalt acted tbkkened basement membrane may even be in like manner on the lung tissues. It may denuded (Fig. 3C). The major bronchi and be recalled,1 however, that whereas a 5 mg. bronchioles have largely recovered and are dose of cobalt metal appears to have no acute universally patent, with* very little desqua toxic effect on guinea pigs when introduced mated material in their Jumina. Some peri intratracheally, repetition of this procedure bronchial fibrosis is, however, apparent (Fig. killed the majority of animals, and the prob W). ability that this is a sensitization phenomenon The parenchymal cellular deposits no has already been suggested.' longer are present. Isolated alveolar walls The proliferation and metaplasia of the may still show residual infiltration or thicken epithelium of the respiratory passages are ing. Rarely, 6brocellular foci may be found, reactions of potentially ominous portent. with marked interstitial cellular proliferation. While a great range of occupational environ In yet other such fod, macrophages and mental dust exposures may lead to bronchitis, giant multinucleated cells predominate. Along bronchiolitis, and asthma,* the underlying the lung periphery there are multiple areas tissue reaction is usually of a chronic sub of vesicular emphysema, and interalveolar mucosal inflammatory nature without epi septa are interrupted at numerous points. thelial hyperplasia. Cobalt and tungsten car The hilar nodes show persisting foci of bide mixed with cobalt apparently constitute endotheltoid hyperplasia which may be cen an exception to this rule, tltough chronic 143 I SCflBPBBS experimental exposure of animals to Diesel The response of bag tissue to the inhalaexi&ust scot and to Schneeberg rock drill turn of tungsten carbide and cobalt in a ratio (fast * has previously been shows to provoke of 3; I provokes an acute inflammatory reac epithelial hyperplasia. It is possible that is tion which is later replaced by focal pneu the case of the latter the cobalt is the tnme monitis and residual bronchial epithelial ore is the factor ia sUmuiatfhg the growth hyperplasia and metaplasia. of the epithelium, While tlw information saw furnished i* uwaffiacnt to warrant more than speculation about the possibilities of this effect ol the cobalt on respiratory epi thelium, the growing toll of lung cancer Justifies further exhaustive study of this phenomenon. suhssassy The intratracheal introduction of 150 mg. of tungsten carbide and cobalt in a 10; l ratio produces a transient inflammatory reac tion, with residual papillary hypertrophy of bronchial muco and peribronchial and peri arterial fibrosis in the vicinity ol retained particulate matter. REFERENCES 1, Delates*, A. 8.: As Experimental Study of the Effects of Rare Metals on Animal Lmjgs, A. If. A. Arch. Jndtirt Health, this issue, p. 11& 2. Schepers, G. W. H.: The Biological Action of `Ttmg&iat Carbide and Carton; Studies oo Evperiroaul f^ubnunary Histopalhology, A M. A Arch. IndusL Health, this issue, p. 337. 5. Stfcepers, {. W. H,: The Biological Action of Partiealwe Cobalt Metal: Studies on Experi mental Pubwnary Hiswpatiwiogy, A if. A. Arch. Irvdust Heahb, this itstie, p. 127. A. Fkaang, A J.; P'Aloaio, C A, and Zapp, |. A: Ukm Occupational KSedkuw. PhJkdrif'hik Lea 4 Fabler, 1954. 5. $ehep<*sr G. W, }L: industrial Asthma sad Broccbitis, lodat Utd 1*5$. She Puimonary. *)Ual>iiity. oCeg.islution ofSouth Jfk nca A ftstteeofe ter Ht EftsctswM S. Vf. H-SCHUHtt, W.Cv5c-SorMxL<4fl. R V. The enactment of the pulmonary disability legislation of the Union of South Africa fol lowed the report of two recent Governor General's Commissions pertaining, respec tively, to the occurrence of diseases attrib utable to the nature of employment in and about mines1 and to the functioning of the Silicosis Medical Bureau.* At the same time it represents the culmination of a protracted Struggle for greater health protection of the personnel cot only of the gold mines but also of all other types of mines in which respira tory hazards have been known to exist but which did not appear to be taken care of by the existing sUieosU kgi&Ution. The hsstori; cal background for this Amendment of the Sdicosis Act has been sketched in the pre ceding paper concerning the progress which batbeta made m the conquest of the occupa tional chest diseases at these mines.* The legislation* was introduced during 3952 as an Amendment of the existing Silicosis Act.8 DEFINITION OF PULMONARY DISABILITY The main point about this legislative in novation is the legal definition which was introduced and which reads as follows (Act 63 of 1952, Paragraph 2, Subsection f3}): "PuhaOBiry disability" means an impairment of the cardfO-respiratcvy functions of a person which, fo the opinion d tta Bureau-- Recorded for publication April ?, 1955. Director, The Saranac Laboratory, (A ) has sutsttnuaily and permanently diminished the capacity for manual work of the person in question; and (B) resulted from the performance, by the per- soq io question, of work in a dusty occu pation; hue does vaK include &r ntfeetcolosu; and for the purposes of this Act a person stall be deemed to be, or to have bees suffering-- <i) from pulmonary disability in the first stage, when the Bureau has found him to be, or to have been, suffering from pulmonary dis ability which, in the opinion of the Bureau, does not, or did not, incapacitate hisev (tom performing moderate manual work, bat dees or did incapacitate Ism permanently from performing manual work more strenuous than moderate manual work; (ii) Ithti pafcncnary disability in the second stage, when the Bureau has found him to be, or to have been, suffering from pulmonary disability which, in. the opinion el the Bu reau, permanently incapacitates or Inca pacitatedhim from performing manual work more streaoous than light mamul work. As this uew legal definition excludes both tuberculosis and silicosis, its full significance can be made dear only after the legal defini tions for these concepts have also been quoted- They are as follows (Act 47 of 1946, Chapter 1, Section 1, Subsection (1|); "Silicosis" means any form of pneumoconiosis doe to the iahalation of mineral dust; and for the purposes of this Act a person shall be deemed to be or to have beea suffering-- (A) from sittcosis in the first stage (which cor responds with the ante*prfn>ary stage under the 1925 Act! when the Bureau has found that the earliest specific signs of silicosis, detected by any means whatsoever, are or were present in the lungs of the person in question, irrespective of whether his capac ity (or 'WQ& has or has pot been impaired by the said disease; or <B> (tom silwosH m the aecond stage (which corresponds with the primary stage loafer Ui SCHF.PEFS the 1925 Act) when the Bureau has foetod that ooderatefy marked specific signs of svhtosh are or were present in the lung's of the persoQ itx question and ska* the said disease has sot incapacitated hit from jvtrfo/minjf moderate manual work; or (C) trcm siKtosh in the third stage (which cor responds with the secondary stage tinder the 192S Ait) when Are Bureau has found tfiat marked specific. Ugtsa ot siUtosis are or were present trt the Jungs of the yer&ao in $ot*> lion and that the said disease has incapaci tated hits from performing moderate manual work. oi the functional -incapacitation used as its differentiating criterion. The financial bene fits and legal restrictions which accrue in re spect to each of these conditions have there fore been equated through the Act, Tuber culosis is treated on a different basis. Second-stage silicosis is likewise broadly equaled to first-stage pulmonary disability* However, there is an important difference here In that, while first-stage pulmonary dis ability necessarily presupposes partial in capacitation, second-stage silicosis does not Apart from the initial absurdity of equat ing the specific disease "silicosis" with the generic term "pneumoconiosis" (which, though repugnant to the medical profession, the lawyers, however, found a satisfactory type of legalistic figment to employ), this definition appears straightforward enough until hs Mi iroplkatioas are more critically analyzed. Probably it will be immediately evident that by equating "silicosis" with `'pneumoconiosis" no true lega) definition has yet been created, as "pneumoconiosis" is not itself defined. 'Jibe tuberculosis definition similarly ap pears superficially satisfactory, reading as follows (Act 47 of 1546, Chapter 1, Section 1, Subsection fl)); '"Tuberculosis' means tuberculosis of the respira tory taffcjn and a person shall, for the purposes of this Act, be deemed to be suffering frora tubercu losis-- and may be certified on radiological criteria only. The South African law emphasized this difference further by providing that when second-stage silicosis and first-stage pulmonary disability are present simulta neously the person shall be deemed to be in a stage equivalent to third-stage silicosis. Again, when pulmonary disability is the first stage is found in association with silicosis in the first stage, the law provides additional cash financial benefits for the affected per son, in principle again presuming that he suffers from two separate diseases. Pul monary disability in the first stage found in association with tuberculosis is equated to third-stage silicosis for purposes of financial benefits. Though the definition specified that pul monary disability could he legally certifiable by the Bureau only, the law got around this by providing for the appointment of special (A) if the Bureau has io4 the sakS pentm'i sputum to contara tubercle bacilli; or (B) If the Bureau has found the said person to be suffering from `closed' tuberculosis which seriously impaired bis working capacity. To the discerning mind this definition is equally full of loopholes. Taking both defini tions on good faith, however, one may as sume that the South African laws intended silicosis or tuberculosis to be certified present committees whose decisions would be deemed to be findings of the Bureau itself (Section *5, Subsection |2), Paragraph (AJ). The Ministef of Mines accordingly by special proclamation created such a Pulmonary Dis ability Committee and defined its powers and mechanism of functioning.* The exclusion of sifacosis and tuberculosis from the definition of pulmonary disability is the first issue to which attention should li when detectable and had now added a new entity, namely, pulmonary disability, to be likewise recognized if it existed. It will be apparent that second-stage pul monary disability is equated to third-stage silicosis in respect to the degree of severity addressed, as this makes for an intentional fundamental legal distinction. The first in terpretation which needs Jo be considered may be that the law intended to distinguish between "silicosis in the third stage," "dosed *d*rcu!&Ms" and "pulmonary disability in 146 PULMONARY DISAStUTY LEG}SLATION the second stage/' m all three of which a segments, or any of the many physiological serious degree of incapacitation for work is combinations which may be found in indis a prerequisite to diagnosis. This may have posed miners and which ultimately lead to been a device of the legal draftsmen to ob anoxemia and cor pulmonale. The whole viate certification of more than one compens group of functional effects thus produced able disease on the basis of the same set of would now be classifiable as pulmonary dis diagnostic criteria. However, the phrase ex ability. It is doubtful whether such a hetero cluding silicosis and tuberculosis from the geneous selection of effects could be included pulmonary disability definition is introduced in a definition of silicosis, having regard to before its two stages arc defined, so that one the fact that there is fair agreement that this must presume that first-stage pulmonary dis is a nodular disease of the lungs. Nor would ability must ako exclude both tuberculosis the concept pneumoconiosis readily embrace and silicosis. The legal experts made a fine all these conditions, as it is generally assumed point by explaining that what was intended to have at least an element of pulmonary fi was that silicosis, tuberculosis, and pulmo brosis to it. It is also well known that there nary disability are to be regarded as three ts no predictable or necessary correlation be distinct medicolegal diseases, each capable tween the degrees of morphological changes of causing incapacitation in its own peculiar associated with the pneumoconioses and the way. The clue to further understanding of this subtle distinction resides in the introduction into the pulmonary disability definition of the words "an impairment of the cardio-respiratory functions/' Silicosis and tubercu losis are thus regarded as morphological dis eases, and it is to be presumed that any dis ablement which they are capable of provok ing would be due to direct effects, sequelae, or complications of the anatomical lesions caused by the inhaled dust or tubercle bacilli. Pulmonary disability, on the contrary, is to be viewed, in terms of this distinction, as a physiological deviation not neces sarily associated with the specific type of structural tissue reaction generally associated with the concept, pneumoconiosis or silicosis. The extremes of contrast envisioned may be illustrated by com paring the incapacitation which may result from massive pulmonary fibrosis {such as may, for example, occur in advanced silicosis, tubcrcuiosilicosis, asbestosis, or anthracosis) with the disability which may be more subtly yet irreversibly engendered by factors such as bronchitis with bronchospasm, alveolar degree of disability which may be found in the affected person. This may be because a multiplicity of factors differentially col laborate in producing these separate effeets. Thus it is possible for a miner's x-ray film to reveal advanced macronodular silicotic in filtration or extensive tuberculosifootic con solidation without any associated subjective disability or material incapacitation for physi cal exertion. On the other hand, a working colleague from the same mine, with a much shorter industrial history and the merest scin tilla of mlcronodular dust reaction, may rap idly become a respiratory cripple and may die at an early age from cor pulmonale. It had not previously been possible under South African laws to admit more than first-stage silicosis in the latter type of esse, and the Pulmonary Disability Amendment was in tended to bridge this gap. Attention must be drawn to the fact that the definition of pulmonary disability differs from that of silicosis (pneumoconiosis) in a further significant way, namely, with regard to the etiological issue. Silicosis, or, for that matter, any pneumoconiosis, can be conceived of only as a disease arising from the effective membrane thickening or impairment, degen occupation of the lungs by mineral dust, and erative changes affecting the lung reticulum in the absence of a specific type of tissue re and elastic system, emphysema, capillary or action to such dust, there can be no question arteriolar occlusion, vascular short circuits of silicosis or* pneumoconiosis. Pulmonarv with reduced perfusion of aerated pulmonary disability, on the contrarv. is defined as a U7 l SCHEPBRS cardiorcsplratory functional Impairment re sulting from the performance of wprk m a dusty occupation. It may, therefore, be due to the inhalation oS mineral dust, as is sy cosis (pneumoconiosis), or it need not be due to such mineral dust. A chest condition arising from nomnmeral dust encountered during mining operations /e. bacteria, fungal spores, rotting timber, chemical fumes, smokes, and gases) esm in no circumstance be called silicosis or pneumoconiosis. But such conditions became certifiable as pulmo nary disability m terms of the neve Sooth African legislation. Pulmonary disability, furthermore, need cot, in terms of this definition, arise as a result of the inhalation of dust, even though reference is made to dusty occupations. The stress is on the words "performstfict of 'work " Injurious environmental conditions which are inseparable from mining, such as exces sive humidity, temperature fluctuations, re current infections, exposure to fumes, gases, or smokes, overwork, and radioactivity, may all in theory' collaborate in provoking tht syndrome of pulmonary disability in a person performing physical labor in such adverse circumstances. In this case thea puUwwwy disability rates as the generic concept, and the disability resulting from silicosis (pneu moconiosis) or tuberculosis may also be in terpreted as a specific manifestation limited to reaction to dust deposition in the lungs, had these two conditions not been specifically excluded by the wording of the pulmonary disability definition. Indeed, had there been no silicosis definition in the third stage or a definition of dosed tubetculcftvs, the pulmo nary disability definition would have ade quately taken care of all the cases which are now classified under such headings, STATISTICAL EELATIGNSHIPS BETWEEN' PULMONARY DISABILITY AND INCAPACITY RESULTING PROM SILICOSIS AND TUBERCULOSIS Since the promulgation of the Pulmonary Disability Amendment, approximately 1000 white miners alone have been certified to be suffering from this condition. In about <methrrd of these eases, tbe'pulmonary disability was found as as isolated phenomenon, i. e,, without siUcosi* or tuberculosis. Of these cases, more than two-thirds were instances of disability m titc first stage and the balance were in the second stage. In the remainder, pulmonary disability was found in association vii\h sftcoris or tuberculosis. In Table 1 the relative prevalence of these conditions for the period 1953-1954 is presented. It will be im- Tabia I.--Prevalence of fulmentrjr Dttobililf in Relation to SHuosis and Tub**e*lotis SwUt African GoSd Mines White Miners--Period 1953-19$4 4............ 41m to sue* 1 Pfij* SfttMiS 8u*t rhit BOcoeB SUge* US ~ Pius BUieoaB StaceS \ at PaireoEurr Dittbtiir* Pius Toben AJpoe kb Pto* satcptb 8Ufel * gtaje z P5tt SHieoUs stun *r v& PUM SU(i i Plus 7vbe> eutostt U Taw* 2.--Prn>Q)e*<t of Occupational Chest Diseases Sowh African Cold Mine* Period I95M95* Soarx Whttf Kfnm.AflVrQxt. maU)r a, SfgrO Isboffrt, ppro*J> W* CHsflhlBty AJom sea TVOes. Sittf*)* <ufor73 * 0 b> ? 16 etegi t56 Sflwsi* Stifti TvUnaltttte Stags' Aioae 3 s 2ASC <a r<* T%1 t.m s.xs PULMONARY DISABILITY LEGISLATION mediately apparent that the prevalence of ers itself militated against the certification pulmonary disabiGty proper is inversely pro of a separate condition of pulmonary dis portional to the seventy of the associated ability, as, in the case of Negroes, full finan silicosis or the presence of tuberculosis, cial benefits accrue to men on first certifica To gain a dearer understanding of the tion of silicosis or tuberculosilkosis or when relative incidence of pulmonary disability tuberculosis is fouad after completion of an in relation to the other occupational chest aggregate of eight years of service. No legal diseases, recourse must be had to the data purpose could therefore be served m exam assembled in Table 2. For the white men ining such men for pulmonary disability, and the figures under each category are self- they were therefore not sent for assessment explanatory. The infrequency with which of their incapacitation. The Heroes who pulmonary disability, as a legal syndrome, have left the mines rarely return for subse is found in association with tuberculosis may quent reassessment of their condition, as be particularly emphasized, and it is also to there is no proper legal provirion for routine be noted that it is much more prevalent than examinations of this type and they are mostly tuberculosis itself. The very high total fig too ignorant to know how to set about lodg ures for this period are also artificial and ing an appiicatiem. A Negro who already lias explained elsewhere.* Silicosis and tuber some symptoms of disease is not likely to be culosis may have to be scaled down to about persuaded by a recruiting agent to return one-third or one-quarter of the cases men to the mines. The statute of limitation in the tioned here in order to obtain the probable case of current miners, moreover, is one yearly rate of production of new cases, the year, and in many instances where some present excessive series representing an ac form of application is lodged either by the cumulation of delayed certification which are bang dealt with. However, tins period is deliberately selected for purposes of com parison, because the pulmonary disability Negro tdwiWs behalf this w done too late, ft is probable that the condition of pulmo nary disability is quite prevalent among the Negroes already acknowledged to be suffer cases are also derived from a retroactive backlog of five years which the law took cognizance of. As the cases reflected in the Table represent the totals discovered among a little more than one-third of the applicants, it may be possible that the annual rates of development of the condition will stabilize at about half of the present figures. Perhaps it will be even tower, as many of the disabled ing from silicosis or tuberculosis, but it is to be doubted that it is likely to occur in as great proportions as among the white miners, ft must be realized, however, that the ma jority of Negro laborers are relatively young men who spend a comparatively short, time in the mines only. In comparable circum stances there need be no reason for any dif ference in pulmonary disability rates in the men bad suffered from their complaints for 5 to 15 years, 11 later, when the backlog has been eliminated, the condition is likely to be certified promptly, as it develops, it may be that the annual production rate will de crease to perhaps an even smaller fraction. two races, unless the more highly developed pulmonary lymphatic system of the Negro is likely to influence the underlying patho logical process unduly. The probable statistical relationship be tween pulmonary disability and silicotic in The numbers of cases found among Negro capacitation is graphically represented in laborers is surprisingly low, having regard Figure 1. In this diagram the serial annual to the large numbers of new cases of silicosis certifications of second- and third-stage sili- and tuberculosis which were found among cotics among living white miners has been them during the same period. There may plotted for the period 1916 to 19S4. In con % be relatively simple explanations for this. structing these slightly idealized trend The fact that so many cases of silicosis and curves, the recent high rate of certification tuberculosis were found in the Negro labor has been ignored for the reason that many H9 i Jw . ' ,~'i. i (500 MdQ 900 B?00 SOUTH AFfttCAW SOtO MINES WHITE MINERS HISTORICAL . W?t6(N OF FW-WONARr OiSAfeUTY *"-< THROUGH MWBSESStVE OtSSCCIATtON BETWEEN FUNCTIONAL IMPAIRMENT ANO RAOIOBRAFWC EVIDENCE OF SILICOSIS SCHBPBR! A. PULMONARY QttM.'TY VWH NO SILICOSIS 0 PULMONARY OISA&UTr WiYvl tUlCO*** C. SCC0W5 STABS SfLtCOSS O THlHD STASE .fCOSf$ 9M m . 1920 140 SdB 149 1932 #45 f93B J9* AttWAL ASSESSMENTS F|OUft I 1944 #4? 940 J9 cases belatedly certified as third* Dr fc^'^-stagt sfficotics were sufficiently dis- mcrit certification but did not qualify Jr m respect of the standards em7b/'1* by the Bureau in previous years. ft*// have been included in the group desig* h( fi pulmonary disability with silicosis. ty 'w curves for pulmonary disability and tiv/j'l* plus pulmonary disability, respec- &o/. re imaginary but are reconstructed st7: J 'r excess of case's of third- and secondwp/1 'hjtxtsis combined with the JOCO cases ' ^nve already been found among about Abify *'l Approximately 6000 pulmonary <U*- rnc `ipplicants, representing the cutnula- jj'c for a five-year retroactive period. e*!'11 j use is made of personal intensive 59*f ''h.,. with these men dating back to *thue" ,, uliHoiiary disability dissociated from lent 1,1 of silicotic nodulation was preva sunikl pi then and may therefore be pre- as w, ^ ''We arisen *t tvtn easier periods i$G it went tmtecogniaed. The main point brought out by this anal ysis is that, while the annual production rates of the third and second stages of radio logical riKoOttS decreased at a decelerated rate during the past 40 years, {be rate of production of pulmonary disability increased progressively and in two phases of progres sive dissociation between {he presence of radiological silicosis and the degree of de monstrable disability. During this protracted period, four funda mental changes occurred among miners on the Witwatersrand, namely, they survived longer, worked longer, developed less tuber culosis and radiological silicosis, and breathed a diluted, moistened, and perhaps altered dust under steadily changing subter ranean environmental conditions of heat, hu midity, ventilation, barometric pressures, etc. In addition, the men were now a highly se lected group, mainly of indigenous South African stock. Which of these many factors PULMONARY DISABILITY LEGISLATION \ stands out as a probable correlate and cause a function 'of duration of dust exposure. o( the disability? There are equally large numbers of miners Altered service periods may be considered who show undue susceptibility or manifest first. To probe this possibility, 155 cases of abnormal resistance to the disease. first-stage pulmonary disability not asso Pulmonary disability is shown to behave ciated with tuberculosis or silicosis wctc in two distinct patterns according as it is analyzed and compared with the patterns associated with radiological signs of 6ilicosts characteristic of the latter two diseases. An or occurs independently of such x-ray signs. additional 90 cases of first-stage radiological The latter group appears early, and those silicosis combined with legal first-stage pul with associated stUcosis have a delayed onset, monary disability are likewise included (Fig. although in one extreme example silicosis 2)- It will be immediately apparent that the and pulmonary disability were already pres foot conditions manifest themselves at dif ent m a young miner after only one year ferent service periods. Tuberculosis pre- eight months of underground employment, doounatea in the earliest phase erf 6nst ex Haber suggestively, the group with asso posure, and the majority of cases occur be ciated silicosis represents cases in which the fore the 14th year of service in dusty occu silicosis manifested itself first and the dis pations. Silicosis, on the contrary, except ability later, although, as we are dealing here for a minor group of exceptionally suscepti with &o accumuUuiop, of cases from many ble persons, manifests itself much later, and years previously, it is possible that these men for the 1939-1948 group the modal peak did also develop their disability first and the appears after the 21st year of service only. nodules were superimposed at a later stage. Silicosis is therefore shown to be dominantly The fact, moreover, that in the first group SOUTH AFRICAN GOLD MINES WHITE MINERS OCCUR***C op *rU8RCUL03'S, PULMONARY OSAWLJTr, SILICOSIS At PULMONARY OlSAetL'YY COMBINED WITH SILICOSIS WITH REFERENCE TO THE DURATION OF SERVICE IN DUSTY OCCUPATIONS. !0 12 *4 I IS 20 22 24 26 26 SO YEARS OF SERVICE W DUSTY OCCUPATIONS FIGURE Z \ 40 42 151 SCH&P&RS SOUTH AFRICAN GOLD MINES WHITE MINERS PRODUCT* RATES PERCENT OF PULMONARY OlSASlLfTT AT OtffERgNT AGES COM PARED WITH THE AVERAGE ANNUAL ACES OF TyeRCm.OrtCS, SlLJCOTICS AND TUSERCULOSlUCOTJCS FOR THE PE0> *6 TO 1952 ACE OF MINER IN TEARS FIGURE 3 of pulmonary disability sufferers there is sot yet say evidence of nodular silicosis does not predude the subsequent development of such nodules. 2t will he eoted that the large majority of these men had become function ary incapacitated before the ]8th year of their service in dusty occupations, j. c., be fore the modal peak for silicosis manifests itself ' An analysis of the ages of the men certified as suffering from pulmonary disability im mediately disposes of any theory that the cause of the disablement may reside in the longer survival of the men, so that jo large measure disability is merely a manifestation of ao aging process in the lung tissues and pulmonary blood vessels of the dust-exposed worker (Fig. 3). The dispersion of the various ages of a group of 155 disability suf ferers vjho had fio associated radiographic silicosis was plotted against the average ages of sibcotics, tuberculoses, and tubcrcuiosilicotics certified successfully in the years 1916 152 to 1952, It is immediately apparent that the majority of siiicotics are almost a decade older than the sufferers from pulmonary disability. TubercuJosiiicodes are likewise muds older. Only the tuberculoses ate., on a average, younger than those who have been classified as suffering from pulmonary disability. It is seen also that the curves for silicosis and tubercubsillcosis intersect the current modal peak for pulmonary dis ability at years 1931 and 1938, respectively. This may explain the relative scarcity prior to those times of pulmonary disability before either silicosis or tubercubsiUcosw mani fested themselves in the affect ed individuals. THE NATUHE OF PULMOKAJty DISABILITY The dominant symptoms associated with pulmonary disability in the gold miners of the Wifwatersraod comprise chronic, in creasingly productive cough, progressive exertional dyspnea, transthoracic pain and eemstuttive seasatkms, minor hemoptvses, PULMONARY DISABILITY LEGISLATION predisposition to chest colds, chronic fatigue, malaise asd weakness, feint paisa, and de pendent edema. Jn the severer grades, there may be nocturnal asthmatic episodes, and orthopnea. Physical signs rend to emphasize poor respiratory excursions, the thorax tending to assume a rigid semi-inflated shape, how ever, with some atrophy of the upper portion. Breath sounds assume a harsh truncated character or may be distent and frequently accompanied by marginal crepitations and rhoncbi. Areas of poor air entry and de creased vocal resonance may be found. Slight cyanosis and finger dubbing or curved nails are rather common. While the vital capacity js sot necessarily reduced, the maximal breathing capacity frequently is. Total King volume is sot always increased, but the residua! air may be considerably increased. Exercise tolerance is generally poor, with both exaggerated signs of objective dyspnea and tachycardia. Electrocardiography tends to show all grades of right auricular and right ventricular enlargement and eventually stress, with right partial bundle branch bbck in a high pro portion of cases. Radiographically the main features fwhere there is no associated silicosis) include areas of increased radiotranshicency, alternating with regionally increased linear markings. Broncbcgrapby may display regional atten uation or widespread bronchial and bronchi* olar cylindrical distention. Glandular crypts are often present. The smaller blood vessels tend to be narrowed and distorted, and in many areas their ramifications become mark edly diminished. The central pulmonary arte rial trunks are often prominently distended, befog often double the normal diameter. This distention may reach aneurysmal proportions and affect the primary and secondary tiers of branches. The azygos veins are often prominently distended, The heart shadow is not often significantly enlarged, except in the later stages of the disease, but the right outflow track and right ventricle may be shown to be distended, and electrokymography reveals markedly increased pulsations! amplitude in those fields. . laboratory findings are in the main nega tive except for progress!}'* polycythemia, the packed cell volume often serving as a good index of the gravity of the ease, those cases with readings in excess of 65?& often proving rapidly fatal. Allergies were remarkable for their absence. The commonest clinical syndromes inferred from this array of findings have been chronic bronchitis, with or without associated bron chiolitis, bronchiectasis or broocbiolectesia, and bro&chospasm. Next in order of signifi cance.appeared to be emphysema, with some associated diffuse fibrosis, although the latter feature was not too strongly emphasized as a clinical diagnosis. The most important finding was, of course, cor pulmonale, with or without fiufare. The most fcmarkaWe feature about this cor pulmonale was the degree to which it could advance before terminal failure and the virtual irreversi bility of the latter once it has reached a cer tain critical degree. UNDERLYING PATROUK31CAL CHANGES IN WJrf&NASV DISABILITY Much of the underlying pathological changes m pulmonary disability remain a mystery, ft had been assumed many years ago in South Africa that the detailed pathol ogy of silicosis, tubercnJosiiicosis, arid pul monary tuberculosis of gold miners had been adequately elucidated through the researches of McCne/ WatSaos-Pstcbford and hfoir,9 Mavrogordato,* Simson and Strachac,41 and Simson, Stmchan. and Irvine1* aad that oo more need be added to the sub ject. It was generally accepted that quartz particles less than 3* ia size are the causative agent with tuberculosis acting as a powerful adjuvant; that silicosis is a nodular or mas sive fibrotic process; that the disease can readily be diagnosed in life by means of good radiograms and after death by macroscopic examination of the lungs; that it causes disability by virtue of fibrosis, emphysema, and bronchitis, and that up to 75# of silicotics die of tuberculosis and the balance either of cor pulmonale, intercurrent infec- .............. i * References 9 end 10, 153 1 SOiEPERS ttans, or some unrelated cause. The Bureau envisioned was that, through some as yet had codified all these perate and had not mexpKcabie modifications in the hlstopatho- anticipated the growing quota of ^atypical" loglcaf process, the focus of emphasis of die cases or the introduction of legislation to reaction would shift from the lymph node provide for functional impairments rather M the peribronchiolar and perivascular loci. than morphological deviations. Histological Whereas destruction of the lymph deposits and experimental research was resumed only merely implied dealing with them a* nature after the Allen Commission,1 had indicated intended that they should be done by, inter its intention to recommend appropriate legis ference with the patency or expansibility lation. Indeed, the whole report favoring the and the peristaltic or pulsatile activities of existence of such a condition as a pulmonary trie respiratory and vascular systems of the disability (other than that secondary to sili lungs at their strategically most vulnerable cosis) was concluded in spite, of the very sectors is tomet&og no* conducive lo con negative evidence' submitted by Bureau tinued good health of the affected miner. officials. The essential change is summarized in That the lungs of affected sufferers show Figure 4. extensive chronic bronchitis (with or with At least one possible mechanism seems out bronchtolar stenosis, di&Wttkm, ot dis to suggest nsetf as an explanation for this tention), emphysema (mainly vesicular but altered histopathological process. Withdrawal fcho some perifocal alveolar duct and respir of tuberculous infection as a component atory bronchiole distention), alveolar wall process in the chest disease was one of the damage and thickening, and small blood most worth-while objectives of the antisili vessel occlusion or natrowSag has since been cosis measures. It, however, left the miner's adequately demonstrated. Jn many of these lung without the added factor to lend mo cases there are also microscopic silicotic bility to the fconiophores conducting quartz nodules which would not be demonstrable particles from the alveoli to the lymph nodes by naked eye inspection of the cut surface of the luhg or palpation of the tissues. These lesions are by no means new phe nomena among the gold miners of the Wjt- via the peribronchial and perivascular lym phatics. In the presence of tuberculosis, thesecells are known totravel great distances rapidly, and accumulations of dust may In watersrand, They lad previously been re ported by Mavrogordafo, Simson, and Stracban in connection with silicosis and tubcrcuk)silicosis. Irvine bad summed up the clinical syndrome of silicosis as being ushered such cases be found in the porta hepatis, the cervical lymphatic nodular chain, and even as far afield as the groins. Such lesions are nevei seen in .simple noninfected silicosis. This factor, namely, the absence of a inby a preceding "dust bronchitis,* and Stra- tuberculosis element, perhaps together with chan bad expressed the view that emphyse a reduced,dust load, may thus have slowed ma, aftd not the pulmonary .fibrosis, is the tip the movements of the koniophores. which ^csuse ofcoc-puUtraoak in sibcotsca. ' thus, tended to accumulate and die iff the Mavrogordafo, Simson, an^ Stracban bad perivascular and peribronchiolar lymphatics, all viewed the dust involvement of peribron thereby .exposing these structures to the full chiolar and perivascular lymphatics as a deleterious influence of the quartz, Uis pos transient phenomenon preceding the over sible also that, through the increasing mecha flow of'dust into* the lymphoid,tissue aggre-' nization' and ever-improving drilling and gated throughout the.lung tissue, v the .pleura, ajfd at tlte pulmonary ibjla; .If .been ttritly < assumed that fius. overflow phenomenon was the, important event in the miner/as* jt;led,to* (he ultimate development of the riKcbtiC'noddle. What had not been bhstrag techniques, mine dusts carry higher proportions of the extremely nocuous ultramicroscopic quartz particles. It is possible also that the wator-spraying techniques of dust -suppression have mainly reduced the proporlion" of larger particles in the mine 1$4 PULMONARY DISABILITY LEGISLATION PATHOGENESIS OF PULMONARY DISABILITY DISABILITY PRECEDING SILICOSIS ru*e 4 I -d*--Norma3 pulmonary alvedl, with quartz-laden Vornophores entering mural lymphatics, ^..--Emphysematous alveoli, with partial degenerative mural sequelae of retention of quartz dust, fli.--Normal arteriole, with koniophore* passing through perivascular lymphatic plexus. Arteriole, with delayed koniophore accumulation around it and tndmal thkkeiwtg. Bu--Perivascular fibrosis and endarteriotar proliferation. , Ci.--Normal bronchiole, with komophores passing through its adventitial lymphatic plexus and others being expelled via its lumen from the alveolar spaces. CV--Delayed peribronchiolar koniophore trappieg and bronchiolitis. CV--Peribronchiolar fibrosis, with hypertrophy of muscularis nutcosae and ttiycossl hypertrophy resulting in bronchostenosis and brenchospasm. 2?,.--Lymph node undergoing early and cumulative koniophore infiltration. D,.--Silicotic nodule evolved at the site of the lymph node. II a,.--As for Ai but with more fconiophotes being retained m the alveolar walls. o,.--Emphysema and extensive alveolar wall damage as an end-result of the initial accsmuJMion of qaartt-laden komophores here, 6,^--Early accumulation of koniophores and fibroeyfes around pulmonary arteriole and commencing collagen deposition. , |' b*--Perivascular fibrosis, with continued koniophore and fibrocyte accumulation around the collagen. a1 &.--Abundant perivascular fibrosis and iatima) jhypertrophy. . b.--Perivascular nodules, with disorganisation of muscularis a( occlusion of vascular lumen. Cv--Early peribronchiolar koniophore and fibrocytic accumulation and endobronchtohtss. Cv--Peribronchiolar fibrosis and hypertrophy of bronchfclar musclar layers. ^--Bfoncfookstenosis and broochlolar spasm. e,.--Broochiolectasia. | fi.--Lymph node not affected at early phase of disease. Lymph node remains unaffected at a late stage in the disease. SCHEFBRS atmospheres, leaving the ultramieroscop#: gence of pulmonary disability without asso particles still in aerial suspension. $tich ^ntf ciated or preceding silicosis may be fomtd in qu&rtx panicles 'when' inhaled_would have the retarded transportation of quark particles a more rapid damaging effect on the pul and thrir deposition around terminal bron monary tissues and would kill the fcenio- chioles atl puhwnary blood vessels and in phorcs before these scavengers could man alveolar walls instead of their transportation age to transport them to the regional Ij-mph to lymph nodes. nodes, One might finally interpose a query also concerning the possible rote of elcsiWH such as uranium which are kcvswn to accu mulate in the lung tissues. Answers to ah these questions will come only through further research, REFERENCES 1- Allen, P.j Report of the Cammisskju of Enquiry Regarding: the Occurrence of Certain Discases. Other than Srtkom and Tvbercakuis, At tributable (o the Nature of Employment in and about Win**, Report V. G. 22, 1951, Government Printer, Pretoria, Onion <rf South African SUMMARY The South African legal definitions of pulmonary disability, silicosis, and tubercu losis are compared and shown to enplasise, respectively, functional, morphological, and infective disturbances. While there is t*o apparent statistical re lationship between legal pulmonary disability 2. Beyers, D. Q, K.: Report of *e Gwrassion of Enquiry Concerning the Functioning of the SttfeotH Medical Bureau, Government Printer, Pretoria, Union of South Mricft, S952. 3. Schepers, G, W. R: Occupational Chest Guesses an Gold Miners: A Review of Progress in the Uoo * SwKh Africa, A_ >5. A.Arch Indua. Health 11:33-47 0oly> I95S. 4. Act <o Amend the Silicosis Act, 1946, Act 63, Government Printer, Pretoria, Union of South and tuberculosis, silicotic and nonsllrccrttc Africa. pulmonary disabilities occur at different serv ice periods and ages and 3n Inverse rates of prevalence. Thus nonsilieotic pulmonary disability now is most prevalent in men of an age group and at a service period which precedes the optimum for the onset of silicosis or tubercutosiHcosss. Tuberculosis, however, fends to occur at an earlier stage m the min ing careers and at an earlier age than do aU three of the former. 5. Act to Amend, Consoktue, and Extend the Lsw Relating to Miner's Phthisis, Act 47, of 1946, Government Printer, Pretoria, Vhrion ot South Africa. 6. Uako of. South Africa Government Nonce 306, Gazette Extraordinary, No. 5003, Feb. II. 1933. 7. McCrae, j.: The Ash of Silicotic Lungs, PaM. Soulb African lost M, Rea. 9:1-7, 13. & WatHas-PUchSord, W. aod Hear, J,-. On the Nature of the Doubly Refracting Particles Seen in Microscopic Sections of Silicotic Longs and an Improved Method iw Dttdcttng Siliceous Parti The disease is seemingly less prevaleol among Negroes who tend, however, to de velop silicons, tuberculosis, and tuberculosSJicosis faster than do the white miners. Pulmonary disability without associated radiographic silicosis or with incipient sili cles in Such Sections, Pub). South African lost. M Res. 9:207-239, 1916. 9. Uavtogtrialo, A.: Studies in Experimental Silicosis and Other Pneuraocontoces, Pvfet. Sooth African Inst #. Res. HiU87,1922. 50. Mavrogordato, A.: Coatribution* to the Study of Winer'& PblhWs, Publ. 5eth African cosis is progressively assuming the role formerly played by macronodular and mas sive silicosis in the causation oi physical incapacitation among white miners. T?*e dominant clinical syndromes of which Inst M. Res. I9:M07, 2926. 23. Sbnson, F. W., and Strachan, A, S.: Ob servations cm tfet Origin and Character of Silicotic Lesions as Shown in Cases Occurring on the Witwsicrsrand, Pub!. South African Inst M. Res. 18-.567-406, 3935. pulmonary disability is comprised devolve 12. Simson, P. W.^ Strsciaa, h. S-, *>d Irvine, on the triad of chronic bronchitis, emphy sema, and cor pulmonale. In those cases where dust is the causative factor, a possible explanation for the emer- L. G,: Silicosis in South Africa: A Symposium on <h Histopathology, Pathological Anatomy and Radiology of ti* Disease, Protfeediugs of the Transvaal Wine Medical Officer's Assertion, Spe cial Supplement, 1930. SS6 (Ovaiuating ^t^isa&iiitif in (compensation f-o? Pneumoconiosis THEODORE C. WATERS, SeftWe : In oar approach to the discussion of the L. , .subject which has been asslgoed to me, I fjjg.g':. should like to call to your attention that |:. provisions for the compensation of pneuroo* -^T : ' coniosefl have presented some of the most 1* controversial subjects in state legislation. 2n " ; 22 states,* benefits payable for silicosis or asbestosis are subject to Imitations which ' are not applicable to injuries resulting from - - trauma*; in 25 states,f compensation is not c- payable for partial disability, and with respect |to those statutes providing compensation for v pneimwcomoses, there is extensive variation . is the benefits paid and in the concept of ST*;:1: 'disability resulting from these diseases. In T_ . my opinion, the reasons for this legislative -- ':. hiatus are as follows: : 1. The fact that, bport enactment of the oceepa* tional disease compensation statutes, ao employer beewee liable for the so-called 'accrued'' liability resulting from the eohaJatioa of dust prior to the $.'?$# that the law became effective, f;- 2 Problems incident to the proper diagnosis of the disease. 3. Differentials In the concept of compensable . disease. ... 4, Evaluation of disability. >* Recorded for publication April 7, 195$. Alabama, Arizona, Arkansas, Colorado, Flor- , ids, Georgia, Idaho, Iowa, Maryland, Massacfcts* . . setts, Michigan, Minnesota. New Hampshire, New 5^'* Mexico, Oklahoma, Oregon, Pennsylvania, South Dakota, Texas, Ulab, Vermont, and West Virginia. tAswana, Cototado, Florida, Idaho, Massa- chusetts, Michigan, Minnesota, New Hampshire, r. /w/New- York, Ohio. OkUhorsa. Pennsylvania, South f ; ^akoU, Utah, and Vermont With respect to the first of these items, "scented" liability is perhaps a misnomer, becaudt wh&t iadustfy was, faced vji\h \ipovi the enactment of the compensation statutes was potential liability for pulmonary changes resulting from extended exposure of em ployees to the inhalation of dust prior to the effective date of the statute, We must bear in mind that upon the enactment of the com pensation statutes the employer became an insurer of the health of the employee as to these diseases. He was stripped of his com mon law defenses, and the continuation in employment by employees automatically im posed upon the employer responsibility for compensation. With respect to the diagnosis of pneu moconioses, I do not need to tell this audi ence of the limited general medical knowl edge that existed some years ago, at the time of the enactment of our compensation statutes making the diseases compensable. Industrial medicine has made great progress in this field, although there is still room lor con tinuing improvement. In the trial of any given compensation case, commissions and courts follow the general administrative policy of giving to the claimant the benefit of every doubt; and if there is medical evi dence in the record to support a diagnosis and finding of the existence of the disease, our administrative agencies are inclined to hold that the disease is compensable, ir respective of the fact that reputable, com petent medical testimony will refute an af firmative diagnosis. This reason alone caused great concern those industries having dust hazards and to insurance carriers responsible upon such risks With respett to concepts of disability, we again find material differences in the legis lative provisions of our compensation laws. 157 v WATERS In summary, they fall into tour classifica fairness to the employer and to the employee tions, as follows: 1. Inability of the injured employee lo earn full wages in (be employment in whkh he was last employed? and to the public, 1 feel that the carrying out of such a policy will make the employer an insurer of the health of the employee, whether or not the employee's illness is at 2. Total disability rendering the employee unable tributable to conditions that arc characteristic to perform any further work *tt has (hen occupation or In any other trade, business, or occupation.^ 3. The event <rf becoming incapacitated, either partially or totally, from performing his work hi the 5asA occupation in which he was exposed to the hazard of such dtsease.fi of and peculiar to his employment. Bearing m mbd this change m concept of the basic purpose of workmen's compensa tion legislation, we now come to the fourth reason above set forth, namely, the evalua 4. Tt* event oi becoming incapacitated from per/orn'lng his work or from earning etjuaf wages in other suitable ropV3yrotac$ tion of disability in compensation for pneu moconioses. It has been toy privilege to participate in There can be o doubt that the basic con the trial of a nutnliet of compensation cases cept of "disability" upon the enactment of involving claims for pneumoconioses, and the workmen's compensation laws was to I know oi tvo problem ot greater importance provide monetary compensation for injuries and more difficult of solution than the at resulting in a loss of wage-eanuag capacity tempted evaluation of disability. While the resulting from the traumatic injuries or oc medical profession has improved its tech cupational diseases acisitvg Wl oi and is the nique for the diagnosis of this condition, course of employment Unfortunately, that little progress has been made in the estab original concept has changed. In an effort lishment of some formula for the evaluation to liberate tlie administration of the laws, of disability. Admittedly, the inhalation of compensation hasheen, and is being, awarded dust over an extended period of time will not for wage loss but for what might be cause pulmonary changes demonstrable on termed to be damages sustained by an em roentgen examination. All of us are exposed ployee during the course of his employment to dust, and I ssswot that it coned to irrespective of wage toss. While I admit my say that with advancing age such changes own prejudice ofl behalf oC the employer are inevitably demonstrable. and the insurer, the fact is that our legisla Let us assume that a given employee is tures, commissions, and courts, interpreting exposed to the inhalation of dust, and let and administering workmen's compensation us assume further that such inhalation causes laws, are tending to award compensation for pulmonary ctanges. When does that condi loss of earnings'irrespective of cause. Per tion become disabling within the concepts haps that result is socially desirable; 1 am not of that term as above referred to? When here to argue that point pro or con, but \x\* S should tbe employee subject to exposure be J Illinois, Indiana, Michigan, New York, and Rhode Island. S Arizona, Colorado, Nevada, New Mevuco, Utah, and Vermont. 8 Florida, Georgia, Idaho, Kansas, UtyUd. removed from his employment? When sliould such employee be deprived of his privilege of continuing at work in the occupation in which he may be engaged? What methods are available to medical scfenc* to evaluate North Carolina, South Carolina, and Souib Dakota, partial disability? What methods are avail f Iowa. (Disability not defined in the States of able to medical science to pronounce that Alabama, Arkansas, California, Connecticut, Dela ware, Kentucky. Lcuiaana, Maine, M&uachuuttt, Minnesota, Missouri, Montana, Nebraska, New Hampshire, Nr* Jersey, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Texas, Virginia, the employee is totally disabled? What sequelae result from a diagnosis of partial disability? Should the employee at that time terminate his employment ? Should he be Washington, West Virginia, and Wisconsin.) paid "X" dollars and have that payment 158 r J. EVALUATION Of DISABUJTY * i *' 5 . y i.i 4- . f ,> * effect a release of continuing liability to his employer? Should his ability to procure other employment free from dust exposure de prive him of any continuing benefit under the compensation tew? What methods are avail able to our commissions and courts to pro perly evaluate disability free and clear of pre judiced medical testimony that may be of fered by the claimant? By the employer? Or by the insurer? These are the imponder ables with which we ate faced in our con sideration of this subject. We still do sot know ail the answers Jo these questions, but 1 would like to review with you briefly some of the standard legislativc provisions which have attempted to deal with these matters and to establish directives to administrative agencies ia handl ing claims. The principal legislative pro visions to which I would refer are as follows. . , I. DENIAL OF COMPENSATION FOB PARTIAL DISABILITY From the medical standpoint, the evalua tion of partial disability resulting from pneu moconioses differs materially from scheduled injuries presently compensable for loss, or loss of use, of other parts of tiie body, such as an arm, leg, hand, etc. The Saranac Laboratory has been a leader in medical research attempting to find some method for the evaluation of partial disability, but its present distinguished Director, his pre decessors and their associates, and other scientists engaged in these studies have not as yet found the answer to the problem. Of necessity, the attempted evaluation of a fixed percentage of disability is exceedingly com plicated and ansaftsfaetety. Therefore, the employer and the insurer contend that com pensation should not be paid unless the claimant has suffered wage loss or that com pensation, if any, payable for partial dis ability should effect the discharge of the employer's liability within a reasonable time after termination of employment, Contra, the employee has, in fact, received some injury from the inhalation of dust and development of demonstrable disease. Perhaps legislative provisions denying compensation for partial disability are not thoroughly satisfactory or' fair to the parties concerned with the ad ministration of the laws, but unless and until tire medical profession gives Its ap proval to some method of evaluation of par tial disability, strong arguments may be presented for this type of legislative pro vision, a, COMPENSATION FOR TOTAL DISABILITY No one can challenge the propriety of paying compensation for total disability for pneumoconioses. However, what do we mean by total disability? Under the definitions above referred to, it may mean one of several things: a. The inability to earn soy wages In the employ ment where last employed &. The inability to perform any further work is tbe occupation in which the employee was engaged. e. The inability to earn equal wages in other suitable empteymesn. Under the first concept of disability, com plete loss of wage is a condition precedent to an award of compensation. Under the second concept, the employee must be unable to perform any further work in his occupation. In this class, we are faced with the administrative and court rulings that have the effect of awarding compensation in those cases where the administrative agency is of the opinion that continuing exposure is hazardous and detrimental to the claimant and, therefore, compensation for total disability should be awarded even though the claimant is able to make as much, and in some cases more, in other employ ment In the third classification, the right to re cover compensation Is dependent upon proof that the claimant has been incapacitated from earning equal wages in other suitable employment, j Simply to state these phases that enter into the determination of what is and what is not a compensable claim illustrates the problems facing our compensation commis sions in disposing of issues presented by this disease. j IS9 y-" r\ DWORSKl Fig. 7.--Capacity <d alumautw hydroxide to xmat tjhe progression of a&costs. Expertised BOS--rabbits received 500 mg, of quarts parcdea for one mcsth u 10 eqoai intravenous ayec- tioos; six months later half of the animals received 10 injectwas of Q2% W(OH>. for five weeks. Microscopic section*. A, liver of aluminum-treated showing limited hyalu&auon and partial regressloa of silicotic nodules at cod of one year B, liver of untreated anicnal. how- ing complete hepatic fibrosis at tod of one year. fig. ft--Capacity of mixacardulty fettro&ced aSunamam hydroxide to prevent completely the development of silicosis after six months of exposure to Quartz dust, provided that bo further exposure to quartz dust follows. Experiment 04--guinea, pig*. Microscopic aeotkmv A, luag of animal exposed for six months to inhalation of quartz dust, followed by irttraeatdia} AI(OH). therapy and residence for six months in fresh air; reacticei limited to macrophage accumulation xntUfi the alveoli B, lung of animal exposed for tux months to qoartz dust, followed by intracardial AJ(OH) therapy and a further six months* exposure to inhalation ol quartz dust; Sansa* prelection only; ccttuiar nodules with partial central fibrosis and necrosis. t WATBKS i, VALUE ov MEDICAL BOARDS P* THE STATS ADMINISTRATIVE AGENCY One result of the problems presented by compensation for pneumoconioses is legtsla* live recognition of the value of Medical Boards to assist the administrative agency in its determination of issues presented in claims. The basic questions involved are medical, namely: (a) whether or not the claimant has a disease; (6) the nature and extent of disability. Owing to the highly technical nature of the medical testimony presented on behalf of the claimant or the employer, the need for Medical Boards to evaluate that testimony is imperative. The net result is that now 17 states# have Medical Boards whose decisions are cither conclu sive with respect to die medical issues in volved in the claim or advisory to the ad ministrative agency. In the past, too little attention has been given to the role of the medical examiner in the administration of workmen's compen sation laws. Time does not permit an ex tended discussion of this matter, but I ex press die hope and opinion dial in the future our legislatures and commissions will not only recognize the need for such Boards but accept and enforce their opinions in preference to the prejudiced pinions of witnesses testifying on behalf of litigants. b. Monetary liraiudora of eompeosaiion, award* ing limited compensation for partial disability and escalator provisions for total disability. c> Limitation provisions barring right to recover? dating from the termination Of anploynwot. With respect to these matters, I commend to you for consideration the statutes of Arkansas, Maryland, North Carolina, West Virginia, and Wisconsin. None of them are perfect, but tliey have attempted to define some method for the proper compensation for partial disability with termination of continuing liability of the employer. Perhaps the most grievous defect in all statutes is found in those sections dealing with limitation provisions relating to the time when claims must be filed in order for them to be compensable. This is a major problem and one which presents the opportunity for extended discussion. From the standpoint of the employer and the insurer, they desire the termination of ltabil;ty within a reason able period of time after employment has ceased. From the standpoint of the employee, he feels that he is entitled to compensation beginning at any future time when the dis ease becomes demonstrable or disabling ir respective of the date of termination of bis employment. Certainly from the standpoint of legislation, we do not know the answer to this problem. CONCLUSION * EXISTING LEGISLATIVE METHODS PROVIDING COMPENSATION FOR TYPES Of DISABILITY Time does not permit the detailed discus* sion of this phase of the subject that is merited, and I can only generalize with respect to it. However, I should Vtke to call your attention to the following features of legislative provisions: a. Dn& of compensation for partial disability <discos*d aberwe). tfArizona, Colorado, Gesvrgia, Idaho, Iowa, Maryland, Minnesota, Nevada. North Carolina, Ohio, Oregon, pf.MyVivu8>, South Carolina, Souih Dakota. Texas, Utah, and West Virginia. 160 The foregoing discussion has been pre sented for the purpose of directing our thoughts to those questions, medical and legal involved in the evaluation of disability. I have attempted to address my remarks to the legal issues presented. Our ste legisla tures and our commissions and courts have not found the answers to the problems so presented. In cooperation with our brothers of the medical profession, it is to be hoped that greater uniformity of legislation and administration may develop in this field and that justice may be done to those affected by the administration of our compensation laws. DL IZaJon PUL em in tmCAH A. HOLAOAY, ti, MA, Sail Ufce City PAST EXPSt&KCES Available data are confined almost entirely to the experiences in the Schnccberg and The occupational exposure of workers to joachirmsthai mining areas, of Germany and radioactive dust and gas has only recently Czechoslovakia, respectively, where an ab become of general interest. Interest increased normally high incidence of lung cancer was as uranium became an important and widely found among miners who had worked for sought after mineral. This development has years in mines which were shown to contain resulted in the employment of large numbers high concentration of radon, Peller,* in 1939, of miners, so that a problem that was once analyzed the cancer mortality experienced of apparently minor importance in this coun by the Joachimsthal miners. He states in his try has become one that demands a solution. summary that the miners in Joachimsthal It is the purpose of this paper to present data had a high percentage of cancers (53$>) on levels of radon found in uranium and in > among causes of deaths. This greatly in onur&nium mines, to refer briefly to po&ti-. creased, cancer mortality rate was due to an ble biologic effects, and to make a plea for enormous frequency of pulmonary cancers the careful examination of existing data in the age group from 35 to 54; there was an which should help in the determination of a exceptionally high proportion of primary safe working level of radon and its degra lung cancers, a reduced incidence of cancer dation products. AU uranium ores contain radium, and therefore th% radioactive gas radon is con tinuously produced and is released into mine in nonrespiratory organs, and an increased mortality from causes other than cancer in the younger age groups. After the existence of the cancer problem atmospheres. This gas and its immediate had been demonstrated, measurements were daughters, RaA through RaC, are regarded made of the atmospheric concentrations of as the most important radioactive elements present hs uranium mines from the stand point of their possible biologic effects, The radon b these mines. Evans and Goodman,' in summarizing these data in 1940, con cluded that the average concentration of question .then is: What are tht effects pro radon In the mines was approximately duced by the inhalation of alpha-emitting lOOOwtc (nsicromicrocuries) per bier. radioactive elements? The result of human exposures should provide the data in estab LACK OF ADEQUATE DATA lishing proper working levels, but, unfor Bale * has summarized some of the un tunately, such records are limited with regard certainties in retrospective interpretation of to the elements with which we are now con the foregoing data as an aid to defining cerned. present standards. In the first place, we do Recorded for publication April 7, 1955. Sanitary Engineering Director, Occupational Health Field Station, Division of Sperial Heahh Senwv Public Health Service, U. S. Department of Health. Education, and Welfare (Mr. Holiday). not have adequate data on lung cancer rates in this region of Europe compared with other mining areas where radon was absent or present in low concentrations, and, secondly, the radon concentrations as measured might Presented by W, Clark Cooper, M.D, Medical Director and Chief of the Division of Special Health Services, Public Health Service, Cincinnati * Bale, W. "P.: Personal communication to the aifthor. Idl HOLADAY not be the same as those that were common safe working levels, it still is of interest to in the mines some years earlier. The long compare the reported atmospheric concentra latent period for Jung cancer might mean tions of radon in those areas with the levels that the exposure 10 to 30 years before the that have been found in American uranium development of symptoms was the important mines. During studies of the Colorado one. Plateau mines carried out by the Public From our own work in mines, we know Health Service in collaboration with the that minor amounts of ventilation will reduce Atomic Energy Commission and the health radon concentrations markedly as contrasted departments of the interested states, several with those existing under conditions of no hundred atmospheric samples were taken ventilation. Thus even limited efforts to re and analyzed for radon and its alpha-emitting duce the radon levels io the European mines daughters, The unpublished results of some may have lowered the atmospheric concen of this work are summarized in Tables 1 trations by large factors.1 Perhaps die and 2. greatest uncertainty is due to the complete Table 1 shows the atmospheric concentra lack of information on the atmospheric com tions of radon found in a number of uranium- centralons of the immediate daughter* of radon whose importance as inhaled sources Tasle I.--Concentrations of Radon m Uranium of radiation has been recognized only re Mine Atmospheres by Mining Areas cently. Shapiro 4 has demonstrated that only a minor part of the radiation dose is delivered to the lungs by radon, with about 95% of the total alpha dose resulting from the inhala tion of RaA, RaB, and RaC. Thus a measure ment of the radon concentration only is a Am, vo~ at Xo. HIBM 1................. ............ 11 z................. g............... . ............ t.............. 16.................................. ............ 3) 4 MMtee So. & M 4JM ,I09 S>1 TO Mm. Be, Liter IS,? tiro s$r tsfoo 3J03 B.cte ttfe. So. & ia aw i,ce* UD ta TO poor index of radiation exposure. Even small amounts of ventilation cliange the ratios between radon and its daughters in mine atmosphere, and so it $ impossible to Infer the amount of the latter elements present in the European mines even where the radon concentrations are known. Altogether, it does not seem that such data as we have on human exposures in uranium mines of Europe are reliable enough to be of much assistance in establishing maximum allowable or acceptable concentrations. mining districts. The results are summarized by mine areas. Thus, in Area X, samples which were taken itt 17 mines showed a minimum radon concentration of 130Qw*c/ liter and a maximum concentration of 48*7CO p^c/liter, with a median value of 8300*^/ liter for all samples. It will be remembered that the average concentration in the Eur opean mines was estimated at lOOO^c of radon per liter of air. Table 2 shows the distribution and the cumulative distribution of miners by levels of COLOHADO PLATEAU U&ANtUM MINES radon daughter concentrations. Thus 140 of While we have pointed out that the records the 733 miners were exposed to concentra of European experience are not complete tions between lC00/i**c/liter and 20G0^#*c/ enough to enable us to establish maximum liter, but 469 (approximately 64%) were Table 2--Distribution of Uranium Miners by Radon Daughter Concentrations lum No. of mtcere PCeUrmraetssUt..v..e...b..o. el Blaere................. Per seat.......... 0-1 UA HA ?$S 393 Average (.]) art***!--SeA + BC MedlBD (t!j n>5M)-l,BMC/UWrR*A + RsC" 362 KKM9) n? HA fllT *.t miUUT JUA * RjC' fS SOD 8* WIXC w> 30.! *5? es.9 JOCKfJ> litftt.fl * US 6.2 IH *.0 I&.OOC ' jjfl 156 m 164 RADON PROBLEM IN DEEP-LEVEL MIXING exposed to atmospheric concentrations of 'RsA phs RaC greater than lOCO/**yiiter (lOOC^c/liter of RaA plus RaC' is equiva lent in alpha activity to 500^c/liter or radon at equilibrium with its immediate daughters). CALCULATION <>T HOSE TO LUNGS We have referred to alpha radiation dose to the lungs, and it is interesting to review some unpublished calculations by Bole, (Table 3), showing what the magnitude of this dose may be.f These calculations were based on continuous exposure to an atmos phere containing 10^c of radon per liter, with gft equivalent amount of RaA and SwiC/liter of RaB, RaC, and RaC, Using Tabic 3.~-Astuntpik>*s Used in iht Calculation of Tutu* Dose - i, feU&UOB ic ue mBdatorj Ua Is S4%. t TMh ekeo<s ftasin )o Om rerpUstot^ *jMra osauJ Uwr hste 0KStd tdroutfi Bb.C'. ft. Plftr t** Bt ot Uv decode tlca pn*eoU cj*e om is ib* fw_ 4. The weicirt { U* Au* tf UMs to tw JKD r. t Tfa9 dteQte depUj ot eJpfc* ridUttoo to tissue ta p. . Tfc* Oi )I bnecboj Is Hftfe&Uf *Ml ll JftO UWt **,. ?. Tt* iiOee btotocle efleetfw&eaa e> lpb* pet* tides a 1$. assumptions for retention of dust and weight of tissue affected similar to those used by the Nationaf Committee on Radiation Protec tion, the weekly dose to the lungs from radon degradation products is 0.043 tern and to the bronchi, 0.72 rem, For estimating exposure levels for workers, we should re member that the concentrations of radon daughters used in these calculations are much lower than would be found in operating uranium mines; hence it appears that the respiratory system of a person working in such atmospheres wiff receive a large radia tion dose. For example, a level of ICOO^mc/ liter of RaA, with SOO^e/liter of RaB, EaC, and RaC, will give a calculated dose to the lung amounting to 4.3 rem per week and 72 rem per week to the bronchi. Calculations made using these assumptions give doses in animals comparable to those determined ex- tBaie, V. F.: Unoublisked data. peritnemaRy by Shapiro* This suggests that the calculated,values are an approximation of those which would be received by humans under the above conditions. U must be pointed out in this connection that it is not possible to consider radiation doses to an organ like the lung by the standards for whole-body external radiation. The latter standards were established with reference to the effect of radiation on the blood-forming organs. Such criteria cannot be applied to tissues where the creation of malignant neoplasms is the important factor. non Uranium mines As uranium is widely distributed through out the earth's crust, it appeared likely that mines other than those that produce uranium would also have some radon in then), and this pinion has been confirmed by several studies, Jacoe1 has reported the results of studies in mines in Colorado, and Harris* has reported similar work in New York. In 35 metal and clay mines surveyed in Col orado, the lowest radon concentration found was 10*c/Uter and the highest was 2100 ftuc/lner. This latter figure is not strikingly different from theaverage figure of ICCO^pc/ liter found in the European mines. In the New York mines, the lowest radon concen tration found was 2^c/liter, while the highest was 110 #i#*c/liter. These and addi tional surveys in other parts <A the United States suggest that radon is a normal con stituent of mine atmospheres. BIOLOGIC EFFECTS Sufcrer and Hu/sb ' have proposed that urinary polonium measurements may serve as a rough measure of cumulative lung ex posure to radon and its daughters, since the daughters decay to Pb*`, a lead isotope with a Jong effective balf-Jife in the body and a decay sciieme producing Pon*. In a compari son of the urine findings ot 19 uranium miners of the Colorado Plateau with those of unexposed laboratory personnel, it was found that the miners chronically exposed to high radon concentrations had amounts of 1*3 H02.A&AY Po"* varying from 2ft*/lU<s > which have atmospheric concentrations oi white no polonium was found in the urine of radioactive dust and gas which exceed any the laboratory group. Thus it would appear working levels which have bees suggested for that the misers had inhaled and retained uranium mines. Undeveloped data which radon and its degradation products. wiil indicate the biologic effects of exposure to radon and its degradation products prob A PLEA FOP THE EXAMINATION OF ably exist, but it will require a concerted EXISTING IWSTa effort cm the part of a number of organiza These studies, together with unreported tions to assemble and analyze the informa work by other groups, indicate that occu tion. pational exposure to appreciable amounts of conclusions ionising radiation has been common among High concentrations of radioactive dust miners and has existed for a long time. The and gas can be demonstrated in a high pro existence of such a large group of persons portion of uranium urines. However, ap who have been exposed for long periods to preciable concentrations have likewise been relatively low levels of radiation (compared demonstrated m many nonuranium mines. with those that occur in uranium mines) Adequate data are not available for inter suggests that it might he possible to evaluate preting these concentrations in terms of the effect of inhaled alpha-emitting elements effects oB human health, but h is very im on the basis of past experience. However, portant that standards be agreed upon. Jt is such a study could only bt done is an am urged, therefore, that a concerted effort be where a large enough group of workers tnade to study records of miners who have vrifh a defined working and medical history worked for years in conursmitim mines, in can be followed. This means that the mining hopes that data bearing upon the establish population must be as stable as possible, that ment of reasonable maximal allowable con medical records must he sufficient io deter centrations can be obtained. mine the cause of illness or death, and that the environmental history of the mines can REFERENCES be obtained or estimated from present atmos pheric concentrations and records showing when ventilation was iotroduced. Such conditions are difficult to meet in the United States where miners are a very mobile group indeed. However, it is possi 1. Evans, R, D, aai Oooitean, C-: Dctemuoa* lion of the Thofoo Contest of Air and Its Bearing oo Lang Cancer Hazards to todavp?, }. latest. Kyg. fc Toxicol U:89,1940. 2. Pttta, S<: Lung Cancer Among Mine Workers to Jouhmisthal Human Biol 22:130, im ble that such a study could be successfully carried out in mining areas m other coun tries with more stable populations and more complete medical records. Any conclusive results that would be obtained from an in vestigation of this type -would be of invalu able assistance in estimating the extent of the hazard created by the Inhalation of radio active elements, regardless of whether or not 3. Ayer, H. E; Control of Radon and Its Daughiers in Mines by VendUtion, Report AECU2858, Occupational Health Fiekl Station, U. S. FitoTic Health Service, Sah Lake City, 1054. 4. Shapiro, J.: Aa Evaluation of the Pulmonary Radiation Hazard from Radon and Its Daughter Products, Report UR-29&, University of Rochester Atomic Energy Project, J054. 5. jacoc, P. W.; Occurrence of Radon to Nonuranium Mines in Colorado, A. XL A. Arch. Induct. the study showed that there had been dis Hyg, l$53 cernible effects on the health of the workers* The number of uranium miners is increasing rapidly, and every effort should be expended to obtain information that will permit the establishment of safe working coo4ttiansIn addition, there are many metal mines 6. Harris, S, J.: Radon Levels Found in Mines to New York State, A. M. A. Arch. Indoyt. Hyg. 10:54, 1054. 3, Sultzrr, M, and Harsh, J* B.: Polonium to the Urine of Miners Exposed to Radon, Report UR-266, University of Rochester Atomic Energy Project, 1953. W 'ft? "V' (Current j-^robiem* in 2)udt C^ontroi inWIdatm we6 There are a few open-pit mines. However, C *. CVlSfcH, U.V. TmrsVns, Ontv Carwfe these are temporary tn type because, as the outcrops arc removed, the mining is done below surface. Primary products of the open pits are asbestos, copper, nickel, iron, mag The control ol dust m metal mines presents nesium, and nephelioe syenite. problems that vary in many respects. Tins Daily production of ore ranges from less is so not ely from mine to mine but also than 100 tons to about IS,000 tons, though between parts oi the same mine. Some ol it is considerably more at 6ome open pits. the problems are new, in the sense that they Hie ore ts crushed, screened, and treated by have assumed importance through changed appropriate metallurgical processes. uditiotis. Some are old, still presenting a The risk of silicosis obtains mainly in un challenge. AH, however, are continuing af fairs, inasmuch as constant efforts arc re quired to maintain exposures at a practicable minimum. derground operations, also in crushing and screening. Tins genera! pkture nay he concluded by referring briefly to the Mining Act of On ' This paper deals with the principal prob lems in Ontario mines--problems which, it is suggested, probably obtain in many mines tario. In essence the Ad requires wet-mining methods undergrouad and suitabk ventila tion to avoid exposure to harmful dusts and elsewhere. The text is based on 20 years' association with endeavors of this kind in an industry dial has achieved a fair measure of success in the prevention of silicosis.1 gases. These legal precautions, supplemented by x-ray examinations of the chest and com pensation for silicosis, were requested by the mining industry many years ago and have IKE ki*snc iKWstav oy ohtars contributed much to achievements in the pre vention of this disease. The mining industry as a whole employs some 35,000 persons, about two-thirds of PERMISSIBLE LIMITS Qt ATMOSPHERIC whom have dust-exposure occupations, Most TOSTftSE&S mines arc multilevel underground operations The vexatious question of permissible lim in steeply dipping veins. The veins vary *n its of atmospheric dust deserves comment at width from less than a foot to several hun the outset because it is a current problem ta dred feet and may or may not be branching the minds of many. H win remaio a problem systems. The depth of operations ranges from for years to come, because there arc so many a few hundred feet to approximately 8200 ft. variables which defy assessment. below surface. The primary products of the Most of the silicosis in Ontario had its underground group are gold, silver, cobalt, origin in gold muses, where it would appear copper, nickel, iron, talc, fluorspar, and gyp the amount of quartz in aerial dusu ranges sum. Uranium will soon be added to the list. from 14% to 28%, as determined by x-ray Recorded for piAlicaiion April 7, 1955. Safety Director and 0d Engineer aid Secre tary, Gxnmittee on Silicosis, Mhks Accident Pre vention Association of Ontario. diffraction-patters assays. Although some,research has been effected with the thermal precipitator, all routine dust-sampling and test work at Ontario 1 ciBSOt: mines ha* been danc with the reulax Honimeter Coe the past three decades- . Koaisneter samples are heated to about JGDO F before and after treatmea^with warm 50% tiydrchloric add for two minutes* They are waned at a magnification of X *50 agamst a dark field. The illumination is a 100 watt frosted electric bttlb, placed 9 in. from the mirror of the microscope. Cotutderable research has been done seeking relief from the tedium and eyestrain when counting samples; microprojection and comparison methods have been tested. To date, however, the problem remains. Through the years, we have come to ap preciate that, in our case, konimeter counts of the order of 100 to 300 particles per cubic centimeter (ppcc) are "good''; those, o* tivt order of 500 to 700 oc 800 ppcc are `fair" only, while those in excess of 1000 ppcc are "poor," The am* of the past have been erased for the most part, and the dust coacts at many smtaflsiions and operations perfected in re cent ye&re approximate 100 ppcc. However, we still have problems, and always will have them, because methods of mining, ground conditions, and pcrsouael change. The same applies to other industries. Ontario mines about 2930 in headings a**' stopes. Some companies used Jt ia ail sue! operations. A number of these drills are stilt in service. Utility of the vented ironthead was demonstrated by the fact that if *rizontal holes were properly started the aver age dust count during drilling could be re duced to about 300 ppcc or even, m some instances, to about ISO ppcc. Dispersal of dust was reduced also by increasing the amount of water. This was done (e) fcy paying more attention to pres sures---au important aspect, (b) by ena bling more water to get through the machine itself, and (e), in the case of some bits, by providing more holes for water to be deliv ered the cutting edges. Collaring, or stalling a hole, U the most vital factor in the dispersal of dust at any drill. If this operation k done wet, the dust liberated is net * serious .problem. If it is done dry, the amount dispersed may com pletely obliterate the utility ofall other means to control dust incorporated fa the drill. The industry therefore welcomed the automatic air-and-water throttle when it became avail able in 1938 aad promptly put it ia good use --first on Deyaers, or mounted, machines and recently on some stopera and airiegs. &RIU4NG Drilling is a major operation in any tnetaJ mine. Most of it is done by percussive drills operated by compressed air. Dust sampling has proved, however, that wet drills of this kind stiH liberate undesirable amounts of dust. The diamond drill, a rotary machine, presents no problems in this respect. Much of the dust from percussive drills is caused by air which leaks past the piston into the fronthead of the machine, whence it passe? down the hole in the drill steel as bubbles in the water. As these emerge from the hole, they release dust. The automatic alr-acd-water throttle x a good device when property used, because a lower dust count wit) obtain at a drill so fitted than can be expected at a machine where collaring is done by the old-fashioned method. However, its utility is defeated in many instances by the provision of a handvalve in the hose for water at the drill so that the machine man can control the s&pj^y oS water when starting a hole and minimize splashing. The advent of the steel holder or hole spotter for Leyners helped this situation much. It also improved safety and decreased This condition was improved, liowever, in the so-called "dastless" drifter, which has vents in the froatbead to allow this air to escape. This type of machine had its origin in South Africa. It was introduced into wear in the chuck of the machine by pre venting the drill steel from wobbling. Much good has been done also by a persistent edu cational campaign in collaring. But the prob lem is still with us. 166 VUST CONTROL IN METAL MINES . The light-weight airleg machines and var ious lands of bits introduced in recent years revolutionized drilling practices and re* treated p^fekrrns Vr dm* cotAtcA. The vented frontbeads and automatic air-and-water throttles disappeared rapidly, though they have lately reappeared on light drills. As for die use of bits tipped with tungsten carbide* the dust counts were not nearly so good as expected, especially when some types of chisel bits were being used. The reason would appear to be that sufficient water does not reach the cutting edge. The chisel bit with only one sideholc for water is an ex ample. It is difficult to control dust while drilling holes upward. The principal reasons are ina bility to maintain a seal of water in die hole and the use of compressed air to keep cuttings out of the working parts of tbc machine. Obviously the condition with respect to dust dispersal deteriorates in confined spaces, be ing moat difficult in dead ends such as raises. The remedies are not easy. Manufacturers have improved machines used to drill upholes by increasing the flow of water and de creasing the amount of air by blowing and, in a few cases, by providing the automatic air-asd-water throttle; there are also a few veiled frontheads in service. As for ventila tion, it can be maintained in a timbered raise, but we have yet to discover how to provide adequate facilities of this kind in an untim bered or raw raise. Research to this end is being done. liberated and breathed for a considerable period during the working shift The dust cloud from blasts may be much denser and the component particles just as fine, but the bulk of it is created and removed in circum stances that ordinarily do not give rise to excessive exposure, la drilling, the direct opposite occurs. Moreover, persons working beyond the immediate source of pollution may be subject to its effects, though to a shghter extent than the machine men. Some years ago, investigators in England suggested that freshly fractured dust may be more active chemically than dust which has been made for some hours. The reason con cerns an unsatisfied oxygen valence on tlie surface of the particles. If this is so, there would be further justification to control dust well at drills. Another reason is yet more important. Dust control at these sites is necessary to supplement ventilation. It is perfectly true that good ventilation will provide good air conditions at any.drill. It if. equally true, however, that the application of adequate air circulation is not feasible for this purpose at all drills at all times is our mines. The same may be true In others, Our industry has done much to reduce dust from this source, with beneficial results. During recent years, however, drilling equip ment and practices have changed notably, Field observations have indicated that the time has come to reassess exposures in these Drill dust is important also because of its fineness, a characteristic that it possesses to a greater degree than dust from ore handling or crushing, for example. Hie finer the de operations in order that the operator and the manufacturer of drilling equipment may be guided properly in continuing to prevent sili cosis of this origin. In November, 1954, gree of subdivision, the greater the possi therefore, we commenced a comprehensive bility that dust so produced may enter the series of tests on drilling equipment under ait sacs of the fcsog. In theory also, a dust corrtroWed conditions W an underground loca which is finely divided should have an en tion, Three engineers--two of our own and hanced chemical activity on human lung one knt by a group pf mines--are engaged tissue, in this research on * full-time basis, assisted A further major reason for dust control at by various operating, personnel. The tests drills is not only that the dust is fine and in some circumstances apt to be present in un healthy amounts but more especially that it is will continue at least through April, 1955. When the research has been completed to our satisfaction, a report will be published. 16? .V GIBSON It is our belief that the maker of s piece of Use of a small mechanical shovel in compar equipment, the developer of a process, which able circumstances automatically raised air produces or entails a hazard to health, should be interested in the elimination of that hazard and that the manufacturer is b a better posi tion than the user to design and publicize remedial measures for the equipment which fie markets. It might be good business for him to do so, too. It would help also if purchasing agents were kept informed of dust aspects. dustiness two to four times. Larger loading devices of this kind are in service no* in many mines. Continuous loaders are also employed in some pans of the United States and Canada. This has necessitated a constant battle to maintain good air conditions. Control of dust at mucking machines de pends on the extent to which water sod ven The manufacturers of drilling equipment presently being tested by us are cooperating extensively in this research, and, as for the mines, especially the one where this work is in progress, they are indeed generous in their assistance. tilation are applied. There is a limit to which water can be used in some mines. Heat is the Handicap in a few instances. However, in the majority of such mines the difficulties are due to tlie nature of the material being han dled, for example, talcose rocks and some WINING METHODS Methods of mining andat handling broken ore and waste have been changing too io recent years. Rising costs oi labor aod sup plies hasten many of the changes. There was also the desire or the necessity to extract large low-grade ore bodies by means that were safe and efficient. There are today ex tensive operations in which the ore is under cut and caved, or broken in huge slopes by drilling and blasting long holes from sub* levels on a retreating basis, or removed by some kind of room-aad-piJlar method. The changes thus effected have all added up to a substantially increased rate of pro duction. This, io turn, has meant the creation of more dust The problem therefore has been to get rid oi it The risk of silicosis io these large-scale operations has, however, de creased because fewer men are involved. Moreover, the size of the undertakings is such as to justify the provision of excellent ventilation in most cases. The problems in volved have been numerous. Invariably, iron ores. On the other hand, it would ap pear that in most metal mines the use of water to allay dust has not yet been fully exploited. The ventilation of places where mucking machines are operated falls into two cate gories, Some loaders are operated at drawpoints and in back-stopes. The only problem in the ventilation of these working sites is that oi insuring that the system lor the mine as a whole serves them adequately, Ventila tion oi room-an<5-pillar operations (a system of mining seldom seen in Ontario because of the nature of our deposits but one that is to be used extensively in the uranium mines in one district) has been developed highly in some operations in the United States. The taajority of our mechanical shovels are operated in headings, where auxiliary ventilation is necessary. There is slow but growing appreciation of the importance sot only of removing dust from such places by means that do not pollute other workings but also of maintaining satisfactory drafts at the though, titey have been associated with the provision of major increments to the ventila tion of the mine concerned. face itself. In this connection, experience proves that the best results are obtained by the dual, or pufth-puU, system. MECHANICAL. SHOVELS Years ago, when a hand shovel was used to There are few problems in the practices of auxiliary ventilation. There is, however, a very real one in r^ard to costs, because load cars in a heading, the 6m town could metal ducts ior this purpose are expensive. be held to 150 ppcc if the murk was kept wet. Flexible tubing is not popular in Ontario. its DUST CONTROL IK METAL MINES SCftAPE&S AMD SCfiAMS Development of mechanical shovels to load mock into cars was paralleled by extensive application of scrapers or bocs to drag ore or waste to transfer passes or loading points. The scrapers vary in width up to 6 ft. The boists that puli them by means of cables range in size up to 150 h. p. The small ones are operated by compressed air; the large ones, by electricity. As in the case of mechanical shovels and loaders, control of dust raised by scrapers is important. Water and ventilation are the remedial measures. The majority of the smaller scrapers arc used to move ore and spread hll-in slopes where intermittent cut-and-fill operations are practiced. They are used also in many other kinds of sloping to drag ore to drawpomts of one kind and another, for example, down the footwaii of an irregular deposit inclined at 40 degrees being mined by open-slope meth ods. The task is, as always, to keep the muck wet by sprays and to dilute and carry away dust that is raised. The fact that in many multilevel mines it is not practicable to split the general ventilation to the extent feasible in fiat deposits extracted by the room-artdptliar method is another handicap. These and other aspects in the use of small scrapers suggest the advisability of giving maximum attention to the use of water in conjunction with good general ventilation. In those operations in which large ton nages are moved by scrapers, the ore may be broken in huge stopes of the sublevel type or by undercutting and caving the ground above. It is removed through drawpomts, which feed into a scraper drift, or "scram," beneath the deposit, by a scraper dragged back and forth. The introduction of this kind of mining posed many problems. It was early recog nized that the facilities for ventilation had to be much larger than those serving most other types of extraction. It was necessary, for instance, to rid the scrams of dust and smoke rapidly and thereby to be able to sec throughout their lengths. Cost of pro tfoa was, however, pared to the bone as pr depended on ability to move much muck ii short time. It was recognized also that a from scrams should be taken to surface b untraveled routes in most cases, its dust coo tent rendering it unfit for breathing. Initial designs were based on air speeds of' 85 to 100 ft. per minute in scrams. This has been found not to be enough. Good practice is to use SOJo more. VENTILATION OF LASOE-SCALR OPERATIONS It is at once obvious that die provision of adequate ventilation for this kind of mining is a major undertaking as well as an expen sive proposition, especially in a deep mine. The changes necessary are difficult to ef fect satisfactorily in any existing mine--for numerous reasons beyond the scope of this paper. On the other hand, it is gratifying indeed to see new producers taking full ad vantage of the experience of pioneers in this field. It is always good practice to consider gen eral ventilation when mine layouts axe made. Where large-scale operations, such as those discussed above, are contemplated, it is es sential that this be done. The general ventilation of many Ontario mines is accomplished by the push-pull sys tem ; that is, air is blown underground and is exhausted by fans at or near the surface, preferably in the latter location. The pushpull system is particularly desirable where mining is done by sublevel sloping, caving, and the use of scrams, because the control of air movement is facilitated. Control is vital in such mining, as the workings are huge and the rate of mining is high. For dust to be effectively controlled, the amounts of air circulated have to be large, with the result that much money has to be invested in ventilation. A major problem has been the develop ment of stoppings strong enough to with stand severe concussion. The strong blasts 169 4 ii CJBSO* necessary in this kind of mining require that heavy steel, concrete, and timber be used for this purpose. * Experience has shown also that in some mines it is necessary to install booster fans in retarn air circuits solely to insure that a gmr. group of, say, five scrams wilt get its fair share of the total available ventilation. That is the only purpose of these units. Such fans range in capacity from 30,000 to 60,000 c. w. at pressures under 1 in. water gauge. Some operators would like to use a small exhaust fan at the tail end of each scram but cannot find one able to take the concussion. The new fan capacity installed for general ventilation in Ontario mines since 1938 total* about 6,500,000 c. m. The increment for the year ending 10 April, J955, will be some 700,000 c. ra. Almost all this new venti lation has gone into metal mines, in most jossaaces to serve the kind of mining dis cussed above. BEAT AND COLD It Is pertinent to refer to heat and cold, at least briefly, because they affect dust con trol In metal mines. In some respects wc in Ontario are fortun ate jo having a cold climate. But the blessing is mixed, for it brings with it real handicaps in ventilation. The ground-level temperature approxi mates 40 F. The geothermal gradients are favorable. Mfcencr* reports the following: Ax* TtajLbi.,...................... Kfrkt*a4 l*M*.................................. fc^otr.......................... OraAfc&t 24enejKr&a . 1 P ptr 3 *<. This means that heat is not a major prob lem at Ontario mines. There are, however, a few where it is becoming troublesome. Up to the present, the operators of these mines have been able to maintain satisfactory air conditions by good ventilating practices. Deeper operations will aftet these circum stances. Preparations are accordingly being made to cool air in summer--and warm it in winter--by facilities in which Mother Nature plays a major role,3 170 It is not heat but the lack of it which troubles most mines in Canada. The new producer has no old workings through which subzero air may be circulated to temper it before delivery to active parts. Trouble of like kind is particularly experienced in older mines that are shallow'. In such circumstances, the operator has only two courses to follow: to heat the in* coming air or to struggle through a winter of four to five months, battling ice in the downcast due to seepage of ground water. Cementation is widely practiced to combat this condition. Sometimes it is successful; oftiroes it is not because of extensive fractotea in the ground, The plants to beat air vary in capacity; a few handle more than 1CO.CCO eta. Coal h the principal iutd used. "Coke-By" from a steel plant is employed in one case; fuel oil, in another. Low-pressure steam is circulated through coils of the fin type m most installa tions, Recently, however, there has been a preference for a kind of heating in which air is forced through tubes around the ``6re*p6t.w Installations of this type can be made fully automatic and arc reported to be troublefree, which is not the case at most of those where steam is employed. As a mine ages, its staff gains experience with this problem. The workings deepen, and open ground is accumulated on upper levels. Ground waters tend to disappear from the downcast through fissures connecting with sections outside of the arteries for air or are conducted to the Fatter. There then is more space to temper air. In such circum stances tbyre comes a time when the plant to heat air may be dismantled and a major an nual change eliminated as was done at one Ontario mine two years ago. It must be pointed out, however, that this is the excep tion, not the rule. Fortune sometimes smiles but not on many. cok<xvsk>h The most important problem in dust con trol in any mine is the provision and mainte nance of a stimoiating'interest in this subject. DOST CONTROL IN METAL MINES Management holds the key to this. If its attitude is food, much will be accomplished. If it is not, results will be mediocre. It is recognized, however, that it is as yet impos sible to control all harmful exposures to dust aU the time and in all places where men work arid travel. It is my conviction that, despite the good history of health in some industrial occupa tions, prolonged exposures to high concen trations of any dust do no good and in time may do harm. They are also bad for morale and affect efficiency adversely. REFERENCES 1. ParSamoa, N. F.: A Statistical Stud; of the Known Cases of Silicosis fo the Mining Industry of Ontario, Proceedings ef fee McIntyre Research Foondadoo's Conference o Silicosis, Chicago, Jan 26-2S, 1953. 2. Miseaer, A, t),: Temperature Gradients in the Canadian Shield, Tf< Gasad. lost. Min. & Metal. 62:129-132, 1949. 3. Rntherferd, }. Gh nod Sedgswonfc, V. JC.: Mine Veatilatioc at tl* International Nkfeei Com pany of Canada, IJmifed, Proceedings oi Technical Seaweed, Mines Atoteft Prwsrt&ft Asscoaiion oi Ontario, May. 1954. s > i 171 ^Jle a&Uabiiitp ^dound in person* Exposed to Certain dj>ertfHium (Compound* HAmtX U KAI.BY, KO. 6t In presenting this paper, I have chosen, first, to summarize the evidence for the con viction that there is a man-made disease pro duced by exposure to certain bery^um com pounds and, secondly, to point out the tin folding cliaisat character of this disease. The need for discussing the existence of beryllium poisoning became apparent with the appearance of the article by Shilcn and his group* in a recent issue of Industrie Medicine end Surgery, wnplyiftg that no ill ness has appeared in certain beryllium ex posures in the extraction aad alloy-manufac ture industry. This article and several in trade journals based on it have resulted in confusion in the mindsof thoseresponsiblefor industrial hygiene measures in berylliumusing industries. The fact that no M. A. C. has been adopted by the American Standards Association or the American Conference of Governmental Industrial Hygienists is an index of the uncertainty of industrial hygiene thinking about beryllium toxicity. The M. A. C, levels at present enforced in some beryllium-using operations are figures recom mended by the Beryllium Advisory Commit tee of the Atomic Energy Commission, Di vision of Biology and Medicine, for use in A. E. C. projects. The evidence from Europe is iliat plants in Russia,* Italy,* and Germany f engaged in extraction of beryllium and manufacture of bcrytfiit*! alloys have experienced and re recorded for pubijcaiion April 7, 1955, References 2 and 3. VReftrencM 3 and 6 m ported worker illness. The illness involved both the upperand the lower respiratory tract and was in some cases fatal, Reports from abroad appeared in 1933 and stopped with the beginning of World War 31. Mention was made in the 1936 report from Russia of illcess occurring in workers some distance from operations using beryllium, foreshadowing the American experience with neighborhood beryllium poisoning. Van Ordstra&d* in 19*3 described chemi cal pneumonia m a beryllium extraction and sJtoy-raanufactoriog plant in Ohio. Shilen and associates * reported respiratory ailments and dermatitis from similar operations In Pennsylvania in 1944. Restudyutg these re ports and the 3945 report of Van Ordstrand and his group,* in which they described their clincal findings under the general tern o! beryllium poisoning, one is greatly impressed that the clincal features and work exposures are identical in the European, Pennsylvania, and Ohio reports. Shilen's observation that the illness he found was due to acid fumes rather than beryllium compounds is % minor ity opinion. Illness experience associated with \he wide variety of exposure to acid fumes in many industries does not support his con clusion that such exposures were responsible for the illness he reported. Important evi dence of the crucial role of beryllium in pro ducing a distinctive, acute pneumonitis is sup plied in the report of Aub and Grier.*6 These authors describe a clincal picture and x-ray findings similar to those reported from ex traction plants. The workers whose illness they describe were exposed to dust and himes of beryllium metal and beryllium oxide. In the reports discussed thus far, we are dealing with acute illness. Such illness lias been cor- pisAMirry from exposure to eeryluvm cqmfoux&s related with intensify of beryllium exposure by Eisenbod and associates.1* The worker suffering from aeute beryllium poisoning, unless overwhelmingly exposed, will recover when removed from the coc. taminated working atmosphere and given rest and oxygen as needed. To clinch the cor relation of beryllium exposure with such acute reaction in the respiratory tract, StokInger and his associates11 have shown by careful and convincing animal studies that beryllium is the causative agent. A final cor roboration of cause and effect lies in the fact that beryllium extraction ami aHoy-manu facturing plants that have adopted industrial hygiene measures no longer report cases of acute respiratory tract disease except in the event of breakdown of protection equipment, Much more complex is the evaluation of the 'disease called by our group beryllium poisoning, by others berylliosis or pulmonary granulomatosis erf beryllium workers. Earlier, Gardner liked (lie term generalized pulmo nary granulomatosis or beryllium sarcoid. As our knowledge grows, this latter term seems useful. In Europe, this chronic in dustrial disease has been termed chronic large-celled pneumonia and pulmonary scle rosis. To review fully the published references to chronic disease following beryllium exposure would be tedious. There are well-documented reports of worker illness, with common clini cal features, x-ray findings, lung function dis turbance, and pathological pictures held to gether by beryllium as the common etiology. To reach a common ground in Judging evi dence for the existence of such a disease, let's agree for this meeting on criteria for a diag nosis of chronic beryllium poisoning. The establishment of real beryllium exposure either by exact epidemiological evidence or measurement of beryllium level in. working atmosphere and/or by the finding of beryl lium In body fluids or tissue, together with a characteristic granulomatous, pathological re action, will serve as diagnostic criteria. The industries reporting such evidence erf worker illness are those engaged in beryllium extrac tion, alloy manufacture, fluorescent- and neon-powder mixing, lamp manufacture and salvage, beryllium metallurgy, manufacture of x-ray-tube windows, brass-tube manufac ture, various ceramic operations, radio-tube manufacture, and atomic energy development. No disease is known to us in processing beryl ore or in the use of finished beryllium alloys containing less than 2of the clement. Teb- rock and Machk " have reported no illness among fluorescent-lamp workers after the bttyUium content erf the phosphor was re duced below by weight. This reduction took place in January, 1943, and beryllium was dropped from the phosphor altogether in 1949. Because of the curious delay in onset of chronk beryllium poisoning, a delay which can occasionally be as long as 10 years be tween last exposure and appearance of symp toms, Tebrock and Machk's observation must wait the test of time. These same authors re port that x-ray, electron diffraction, and crystallographic studies show that the upper limit of solubility of beryllium oxide in the phosphor lattice Is about 3?&, with the result that above free beryllium oxide is present. Tebrock and Machle hold this compound re sponsible for the ftfciess in the fluorescentlamp industry. V/hik the evidence that beryl lium oxide is present in most or all beryllium operations flat have caused illness is striking, one nevertheless wonders if it can be true that beryllium oxide alone is harmful. Continuing the documentation of chronic beryllium disease, let us discuss the experi ence in the beryllium extraction and alloy manufacturing industry. De Nardi and asso ciates u have reported chronic worker cases, and Chesser11 chronic neighborhood cases from this industry it* Ohio. lieben " has re ported cases, previously discussed by Jack- son,** of chronic beryllium disease in men working in a brass foundry using a beryllium alloy containing about of the element. The sick workers were exposed to beryllium- containing scrap dust and to the fumes from the melting of the alloy. GoldwaterJ has seen worker illness from the Pennsylvania JGoMwatw, L..: Persona! conHimokatlwi to the author. 173 -{ t HARDY industry manufacturing beryllium alloys which hebelieves can beproperty tfccmneutcd as beryllium disease. Through the kindness of Dr. John Bisbing, of Reading, Pa.( we have recently studied the illness of a worker who was engaged in the manufacture of beiylhusft alloys from 1940 to 1942, This patient worker fulfills the criteria of chronic beryl lium poisoning, Dr. George Chamberlin, also of Reading, Pa., presented an exhibit at the Pennsylvania State Medical Society Meeting in November, 1954, of seven cases he diag nosed as berylliosis. With these clinical re ports, it seems fair to conclude that the Penn sylvania extraction and alfoy-m&mtfacUirittg industries have had illness experience asso ciated with exposure to certain beryllium compounds similar to that reported from European and Ohio industries engaged is these same operations. In reviewing the throe reports of Shilea and his colleagues--one published in 1944,* one in 5949,** and the most recent in 195V a reasonable interpre tation may be that this group concluded, erroneously in oar opinoa, that the worker illnesses designated as beiyllium poisoning by European and Ohio observers were due to inhalation of add fumes. In the 2954 anal ysis of their findings, Shilen's group not only failed to include medical follow-up of work ers no longer at the plant but also did not mention that experience ol physicians in the community who might be caring for possible cases of chronic beryllium poisoning was sought- We know that because o( delay in onset patients with chronic beryllium poison ing are seen first by the family physician, rarely by the plant physician. Frequently, community tuberculosis sanitaria staffs dis cover cases of berylliosis through routine chest x-ray surveys and because the disease can be readily contused with miliary tuber* euJosis. From this case-finding experience, we infer that Stolen's report of 2954 is in complete, and therefore the implied 'con clusion that there arc no cases of chronic beryllium poisoning m workers from the plant studied is not justified. traordinary cumber of reactions, chroaic as well as acute, to die experimental animal. Schepers^ of the Saranac Laboratory, m recent correspondence, has furnished the in formation that pulmonary carcinomata of a triple variety appear with consistent fre quency alter about M months in rats exposed to beryllium sulfate for a minimum period of six months. Assuming by analogy with what happens vr> she experimental dost diseases that one month of a rat's life may be equated to a year of a human life, Sehepers points out that we may shortly expect to know it respi ratory tract neoplasm will appear in die worker population exposed to certain beryl lium compounds. We have at present no clini cal evidence of malignant neoplasm in the respiratory organs in persons with chrome beryllium poisoning. To my knowledge, there ate as yet no studies of the incidence of lung neoplasm in a beryllium-exposed population free from evidence of beryllium disease. In summacy, epidemiological, industrial hygiene, clinical, and animal experimental evidences document the conclusion that dis tinctive disease occurs in beryllium-using in dustries, exclusive of those using finished low beryllium alloys (less than 2^) and those engaged in mining beryl ore. There is ade quate evidence that no beryllium extraction and alloy-manufacturing industry in the Doited States, of which we have knowledge, is completely tree of the vrorker illness, fulfiHiog the criteria UM down in this paper for the diagnosis of chronic beryllium poisoning. Knowledge of the man-made disease,beryl lium poisoning, berylliosis, or whatever name you like, is less than 20 years old, counting all reports, and only 10 years old in the United States. The particular point to be made in the second half of this report is that, as a consequence of its newness, the clinical characteristics, life history, x-ray and patho logical variants of this diseat* ase still un folding, Since this is true, it is not accurate to speak of a classic case ol beryllium poison ing or to insist that a particular case cannotI fn addition, evidence has accumulated that I Schepers, G. W. H.: Personal coinmuuicatfan l*tryJHum compounds ate capable of an ex to the anchor. 1?4 DISABILITY BRQ14 EXPOSURE TO BERYLLIUM COMPOUNDS be berylliosis because the clinical course ap pears unusual. To illustrate the presently known clinical syndromes for the 1955 Sara nac Symposium, the following temporary symptomatic disease or by irreversible Sbrotic pulmonary change gradually diminished lung function. We have followed a simiar case for 10 years without the patient as yet develop classification of beryllium disease, based on ing symptoms. our clinical experience at the Massachusetts General Hospital, is prepared. This descrip tive classification embodies a clinical concep tion based primarily cm the patient's ability to do his usual work. To illustrate the pic ture of chronic beryllium disease, an example of a case in each category will be given. II. BEBYLUUM EFFECT--FBOBABLEDISABILITY An allied category has been arbitrarily called beryllium effect with probable dis ability. This group, in our experience, is growing is si. The case used for illustration is that of a 37-year-old engineer, previously T. BERYLLIUM EFFECT--HO DISABILITY Beryllium effect without disability is illus trated by the case of B. D., a young Italian woman of 33 years. She was exposed to un- good health, who, after a respiratory in fection in 1950, was found to have dramatic chest x-ray changes. Pulmonary tuberculosis was carefully ruled out The patient was re ferred to us for study because of a history of ClasificalioB of Beryllium Diseas* ^^^^s======^^^^^^^^^============== L SkryEBos ettci--ao dlnbSCr II. 8TtQn 8eet--provable dUaMlft? 16 months' intimate exposure to fiuorescentlamp-manulacture operations. Beryllium in the urine established exposure. The man was under great strain because of watching his m. WUlj ymptonatte bcrfEBoa IT. HoOettUir dlaabUar berr&tas Si***# V, Brttttl? CUMUac bef?Biuit dime VI. OMs^eidr <HmMSb* berrMaa di##*## Ytt. BecoixrT from btryHftaa dkuM (A) With K^dual triGtee* of !nvref{&b pstb<dofT (8) Wllb BO CVMftDM Of 41nN wife die a slow and painful death due to cancer. His chief complaint was fatigue and some weakness, acd, if pressed, be thought he was a little dyspocic on real effort. Lung function study showed slight increase in residual air. In 1955 this man feeis well. His present problem is that be finds difficulty in known amounts of beryllium-containing phos phor, off and on, for eight years, beginning in 1940. During a routine chest x-ray survey conducted by the plant where she worked, abnormalities, such as are seen on the film, were noted four years ago. These changes were reported as fine mottled bilateral in getting a job because of his chest x-ray changes. The amount of change shown on x-ray and the mode of onset make it likely that functional disability will appear and pro gress. In addition, the employment handicap of the abnormal chest x-ray may be rated as a kind of disability. crease in densities from the hUum to the periphery, Careful study in two hospitals and lung function studies revealed no other ab X, MILDLY SYMPTOMATIC BEBYIXIUK DISEASE normalities. The worker has no complaints. The next group of wotkers, suffering from She leads her usual life, hindered only by anxkty, because she knows of the illness and subsequent death of several young women with whom she worked at jobs similar to her own. This represents a beryllium effect not productive of symptoms, because the process does not involve enough tissue to embarrass function. The pressing question is whether or what has been designated as chronic beryl lium poisoning with mild disability, is also growing, A typical example is a 32-year-cld man who worked in beryllium-alloy manu facturing between 1940 and 1942, during which period he had a vesicular rash with itching, The skin reaction was mild and did not prevent him from continuing his work. not the process by exacerbation will produce In 1953 a diffuse mottling of both lung fields 175 KAHDY was smi by x-ray. This coiorided with a the add of 75 mg. of cortisone a day, be works severe respiratory infection, a slight weight 40 hours a week but must limit Us social Joss, and the onset of cough and dyspnea on activities In order to rest and has stopped bis exertion, accompanied by intermittent low- 'exercise completely. Infections increase die grade fever. Lung function study in 1954 re dyspnea which is not entirely under control. vealed increased arterial oxygen difference We believe that S. A. illustrates that the at rest as well as on exercise. Biopsy of (be prognosis for life as well as activity is un luttg revealed pathology consistent with a favorably altered in this group in spite of diagnosis of beryllium disease, and the ele cortisone therapy. ment was found io the Jung on speetrographic analysis. This jft&n works every day, repairing air planes. He is* however, aware of dyspnea on effort, increased when he has a respiratory infection. As ia the previous category, mefi in this gcosip have trouble findiflg jobs and understandably become anxious about their future. Since considerable pathology is pres ent, it seems likely that pulmonary reserve is constantly being decreased by irreversible fibrotit change, v. 5SVBXEL? ni&Asxmc s6ryu.kjm disease Iq the severely disabled group of cases of chronic beryllium poisoning, we include women who can do some housework and men who work intermittently at sedentary jobs. Theseverity is judged on the basis of frequent tripe to the hospital, complications, and obvi ously bad prognosis. M. }. illustrates this group, which is, we think, getting smaller in rife, is part because of the character of beryllium disease and in part because of the success of long-term use rv. KODWtArtLy msabmno bejjyluust OJSfcASS In the group of cases suffering moderately disabling beryllium disease, we are concerned with medical management now that cortisone has beets shown to improve luog function, To illustrate tbU group, the case of S, A., a 34year-old accountant, is presented. During 1943-1944 he spent 30 weeks ie a ffoorescent- of steroids. M. /. worked as a draftsman for one year in a fluoresccnt-larfip-manufacturiog plant during 1940*1941. Swereasing dyspnea, cough, and chest x-ray findings of miliary densities brought him to the hospital for diag nostic study in 1952, Beryllium in the tissue and. characteristic pathology were found on lung biopsy. This patient shows narked club bing of fingers and toes, cyanosis, and sec lamp-mamriacturing plant as a cost clerk. ondary polycythemia in spite of cortisone During this time be was in all parts of the therapy. M. has shown bypercalduria (in plant. Beryllium, found in the urine, corrobo dependent of cortisone effect) and relative rated this exposure history. In 1948, S. A. hyperglobuJiuemia, evidence in support of the lost 20 lb. and developed a cough and grad concept that beryllium poisoning is a consti ually increasing dyspnea. The chest x-ray, tutional and not exclusively i pulmonary dis when we first saw him in 1952, was reported ease. Bout?, of headache and fever, two epi as showing reduction in sire of both upper sodes of abnormal depositor of calcium in soft kbes and extensive emphysema with bleb tissue, a fractured rib, and two serious respir formation in both lower lobes, while through atory infections have complicated this man's out both lung fields there was finely mottled course in the past two years. Some of the increased density. I-ung function studies difficulties arc due to cortisone effect, but showed abnormalities in all values. The EKG, at first normal, now shows evidence of right ventricular hypertrophy. without the drug the patient is completely disabled. With encouragement the patient works about hall rime as a draftsman. Should After several hospital trials with cortico he work at aU? for his morale we believe tropin and cortisone, this patient is able to that he should, but there is certainly strain Scad an ambulatory but restricted life. With on his right heart. In this group cortisone m DISABILITY FROM EXPOSURE TO BERYLLIUM COMPOUNDS prolongs life and makes the patient more comfortable but probably does cot change the outcome. VI. COMPLETELY DISABLING BERYLLIUM DISEASE It is possible that there are too many groups in this presentation, but this grouping has been done deliberately to emphasize the broad spread of the clinical picture of beryllium disease and the relationship of these syndromes to disability. The extraor dinary tenacity to life of the completely dis abled cases of chronic beryllium poisoning is illustrated by F. A. This young woman worked in fluorespt-lamp manufacturing from 2940 to 1943. Cough began in 1943; weight loss, dyspnea, and marked x-ray changes followed, until by fate 1945 the pa tient was unable to do anything except the lightest housework. From 1947 on she has been a total invalid, completely dependent on oxygen therapy. To compress a long story, she has had episodes of spontaneous pneumo thorax, pleurisy, erythema nodosum, and epistaxis; she shows cachexia (weight, 75 lb.), dubbing, cyanosis, enlarged liver, and evidence of congestive heart failure. Her bio chemical studies show hypergbbulinemia now and from time to time have shown ab normalities in liver function. This is the type of en** I wrote about in 1946, when the fiuorescem-lamp-roanttfacturing industry first reported an unusual number of cases of what we then named delayed chemicalpneumonitis. Cortisone and corticotropin act in this group also to prolong tile and increase comfort. However; the failure of the right heart mani fests itself as the terminating complication, in spite of complete rest, oxygen therapy, and the use of steroids. symptomatic recovery with residual pathol ogy, He worked In close exposure to the early high beryllium phosphors and was ex tremely disabled for 18 months with cough, dyspnea, and severe gastrointestinal symp toms. He gradually recovered with only sup portive therapy and now works steadily at a desk job. His chest x-ray shows fine densities throughout both lung fields. F. L. has passed three small renal calculi at intervals, a reflec tion of disturbed calcium metabolism noted in a number of cases of chronic beryllium poisoning. Time alone can tell whether or not he will have an exacerbation of bis symptoms and whether his obvious pathology will ma terially alter his life expectancy. There are a small but definite number of studied cases with a similar history of remission. Finally, the case of L. B. suggests that it may be possible to cure beiyllium disease with cortisone, Of course, time alone, per haps, would have resulted in a similar out come. L. B. is a 27-year-old woman who was exposed to beryllium oxide when shaking the material for sizing purpose during 19442945. After pelvic surgery in 1950 and a subsequent respiratory infection, she was troubled by a nonproductive cough and grad ually increasing dyspnea. Her chest x-ray showed nodular densities from apex to base, bilaterally. She gradually became disabled because of dyspnea. 2c 2952 she had evidence of abnormal lung and liver function and was in bed a great deal because of shortness of breath and weakness. Gradually, with the steady use of cortisone after trials of inter mittent corticotropin; she improved until in July, 1954, she found that she was able to work 40 hours a week, and her chest x-ray is considered to be normal. The dose of corti sone has been slowly reduced. VII. 1ECOVERY FROM BERYLLIUM DISEASE After almost 10 years of study of chronic beryllium disease, it is now possible to speak of remission and possible recovery, in con trast to the desperately ill group just de scribed. F. L., a case reported by Cass * and also studied by us, represents a spontaneous. Clinical material similar to that here de scribed is accumulating steadily; Because of the continuing acquisition of knowledge, it h impossible at present to make accurate state ments as to prognosis and Incidence of com plications. There is no doubt that the steroids not only have increased comfort but also have lengthened the lives of patients with chronic 177 HARDY beryllium disease. Our one case suggests tiat long-term cortisone therapy njay result in a true cure. This statement may have to be amended, as we learn of spontaneous com plete remission in beryllium disease. This discussion may serve to sustain your beryllium will be found if locked for. However, it seems critically reasonable that the combination of a gnuatioeatotu reaction and beryllium re ade quate support foe a of beryWum tnttou* cation. It b well to point out that there is no cor- relatioo Ulweeu the quantity of beryllium found m tissue and the pathological reaction. interest in the unfolding facts of this cxtraordinaiy man-made disease. It may well prove that Gardner's informal title .of beryl lium sarcoid was apt, indeed From knowl edge of this disease of known chemical etiol ogy, it may be possible to study the patho genesis of the sarcoid-like diseases of un known etiology, which are so fascinating and so baffling. REFERENCES 1. ShJko, j.; Koppenhavef, F. B,; Cltiaod, J. <2.; Luta, L. R., and Vought, V, U.: Beryllium Extraction, Reduction, and Alloy Fabrication: An Engineering Study Covering Ten Years! Experi ence, lodust Med. 3:291-299 (July) 1954. 2- Berkovits, M>, and Ixrzeb B.: Changes in the Longs Caused by BeryHmm Oxyfluoride Intoxi cation, Klin. med 18:317, 1940. Oeeupatiostal Medical Clinic, Massachusetts General Hospital. 3. Getsun, Li Poisoning by Vapors of Beryl lium Oxyfluoride, j. lodust Hyg. & Toxicol. 18: 571-379 (Sept.) 1936, DISCUSSION Dr. Xovbk: What criteria have been set op for accepting a ease of berylliosis for admission to tie registry? Da. Hardy : The registry U currently just being established, and as /et none of the eases lave been accepted with finality. I have two physicians helping me who have oot been intimately associated with the study of beryilimn poisoning, and dans lend objectivity. In addition, there is an Advisory Committee, which meets annually to help tss, and. finally, we have advice on handling the statistical data and proper recording from the Department of Preventive Medicine at the Harvard Medical School Da. Kovb# : By whst means are other chronic pulmonary grannlotnata distinguished from that caused by beryllium ? Pa. Hardy: I think this question should be answered now is terms of my opinion rather than wliat will ultimately reach the registry because of the above-described newness of that project Since the pathologist* do not agree as the specificity 8&f uniqueness of the microscopic picture of beryllium disease, the finding of beryllium & tissue nm*l be the crucial factor. This seems not unlike bacterial etiology, such as the finding of tubercle bacilli. Da, Kuvek; 1$ the finding of beryllium in tissue considered diagnostic ui berylliosis? Dr, Hardy : 21 beryllium is found in tissue with out pathological reaction, the presence of the beryllimn is interpreted as meaning exposure. Study of autopsy tissue from persona who have worked beryllium-using industry shows the .presence of beryllium as might be expected Because of our knowledge that beryl occurs in many places in the earth's enm in this country, it is possible that 4. Mamdi Fabrod, S.: Atypical PoeumocoiuosU Due to Beryllium Dust: An F^perimeutal Study, Med. bverott:297-305 (Aug. 31) 1935. 5. Weber, H. H., asd Eugelhardt, W. E,: Umersuohung voq Steuben rus der Beryllrumgewtruumg, Zentralbi. Gewerhehyg, 26:41, 2933. 6. Meyer, H. .: Dber Berylliumerkraukungen der Longs, Stitt. Klin. TuberK. 88:388'595, 1941 7. Van Ordstxand, H. S.; Hughes. &, and Cairoody, M, G.: Chemical Pneumonia in Workers Extracting Berylfium Oxide, Cleveland Gin. Quart. 26:10-18 (Jan.) 1943. 8. Shilcs, J.; GaJlowaj, A. Ev and Mellor, J. F., Jr.: Beryltimn Oxide from Beryl: Health Hazards Irvridett to Extractite, lndusa. Med. 11:464-469 (Jan.) 1944. 9. Van Ordstrand, H. S.; Hughes, R.; DeNardi, J. N., and Cannody, W. G.: Beryllium Poisoning, J. A, M. A. 189:1084-1090 (Dec. 15) 1945. 10. Aob. J. C, and Grier, R. S,: Acute Pneu monitis in Workers Exposed to Beryllium Oxide and Beryllium Metal, J. Indust. Hyg. & Toxicol. 31:123-133 (May) 1949. 11. Eisenbud, Mi Berghout, C F, and Stead man, L. T.: Environmental Studies in Plants and Laboratories Using Beryllium: Acute Disease, J. lodust Hyg. & Toxicol. 30:281-285 (Sept) 1948. 12. Stronger, H- E-; Sprague, G. F.; Hall, R, H.; Ashenburg, N. J.? Scott, J, K., and Steadman, L, T,: Acute Inhalation Toxicity of Beryllium: Four Definitive Studies of Beryllium Sulfate at Exposure Concentrations of 100, 50, 10, and 1 Mg. per Cubic Meter, Arch. Indus:. Hyg, & Occup, Med. 1:379-397 (April) 19S0. m r.' DISABILITY PROM EXPOSURE TO BERYLLIUM COMPOUNDS f U Tebnejf, H. * aadliachle, W.: Edok*y M [Octtfk BeylBorit, in.Prfr*diBg>f XMftter- } Congress of Industrial Me&Qne, Hapte* 'aS*t JS-2* JRHA ** R De Nardi, J. M-; Van Owbsrwd, H. S^ and Carmody, M. <X: Chronic Polmohary Granuloma tosis: Schorl of Tm Cases, An. J Mot 7:345- : 355 <Se*> 1*9. j 15. 0*^>C:Ct>rtKte'?it\maaaij Gnmukanatods in Residents a Ctmwnoraty near a Bcryiiium : Plant, Ana lat Mt II: 1028-1043 (Job*) 1050. 10. ShOes. h; MeUor, J. F. and others: Beryl- lhi: Health Hniardsm &e Extraction o* Beryf- finss Oxide from Betyl and Beryllium ABoy hfaao- jbcm-UkM. Md* 18:209-213 (March) 2949. <AV- -y ' 17. Uefeen, J, and Jackson, A- }< Beryllium Oxide Pcttsemug, lodast Med. tg:$Q?Sl3 (NwO 1953. Ift Jarfesca, A. Becyttrom A/toj-s, in Prxa- tnocoroos(s: Beryllium, Bauxite Fumes, Cotnyen- satkm (Sixth Saranac Symposhns), edited by A. J. VonvaH Nr* York, PiyJ B. Barter, Inc. (Med ical Boot Dept, of Harper & Brothers), 1950, Chap. 2, p, 11. 19. Cat*. J. W,, Jr,: Spontaneous Remission of Chrode Beryllium FoUoaing from Floorescest Lamp Hkmzfaetsrzng: Report ofa Case, A. M, A. Arcb. Ifidnst. Hyg. 1:569-570 (June) 1951. J^ ' kcat- [y AA ''A5 fllfe:,':*ghsf^ fv .>. t'-m - CeJ-r'.'-ia.,..:. Sy! <^T wr. v . <* N . A *'- * -w**.-* V -..a < -1 * -- ' ' 5* 179 54 effects of'SnLUDaLWinincf 2W an ilte J4^umcu\ <Jli unp The extent to which the mineral talc is responsible for the changes v the hmgs is 6. W. H. SCHEttRS, M.D. D.$. end T. M. &U*KAN, W.C, Swuoc Uk N. Y. still in doubt. Certainly the experimental and clinical evidence incriminating pure talc as the principal etiologic agent in so-calkd takosis has so far been much less convicting than similar evidence supporting the views . Talc belongs in the group of silicates that that silicosis is caused by inhaled quartz dust have been under suspicion for many years as or that asbestosis is provoked by inhaled a cause of pneumoconiosis. The literature asbestos fibers. Nor is there complete cer contains a number of reports of studies which tainty yet concerning the pathognomonic fea indicate that industrial workers exposed to tures of the specific tak disease. talc dust sometimes develop changes in the la spite of dse uncertainties, reports on lungs, and several investigators have used the 21 clinical and roentgenological and 13 term "tekosis'' to describe the pulmonary autopsy studies exist in the literature, com conation produced wj those exposed workm. mencing with the first paper by Thorel1 ia . Pti^c talc, a hydrous magnesium silicate, is 1896, Jaques and Beoirschke1 have recently a specific mineral, but, as Schul* and Wil reviewed these cases. The main emphasis ap liams* pointed out, the word "talc" as used pears to be on a radiological pneumoconiosis, in industry usually refers to s product which ranging from diffuse bilateral reticulation meets certain physical requirements rather without predisposition to tuberculosis to con than to a substance of definite chemical com glomerate massive shadows frequently tuber position, In commercial talc, the mineral talc culous in nature. Clinically the disease varies itself may be only a minor component Schttlr from a benign to a rapidly developing fatal and William* found that in SI samples of process, with emphasis on cor pulmonale as commercial talc the amount of the fak com the cause of death. There may be aprolonged ponent, based on the count of particles smaller symptom-free induction period. Tuberculosis, than KW never exceeded Stjh of the sample. emphysema, and bronchitis vary in their Other prominent minerals in their samples prevalence. Pathologically the condition has ^ere.sorpentinef*dolomite, and Cremofite. A been described mainly as a dense type of review gt the data on 35 "ink?' samples re fibrosis, with peribronchial and perivascular ceived at The Saranac Laboratory for routine prevalence and sometimes with nodularity. analysis revealed that the composite varied * Talc has been demonstrated in the tissues of widely- lo & of the 35 samples there was oo some cases, and the suggestion has been ad more tHana trace of the mineral talc present,, vanced that the talc shows certain erosion and atl die 35 contained a substantial amount changes in the human tissue not present in of one or more other components,'such as., the original state. A point which has by Iranelite, mica, carbonates, and day min no means previously beesi settled concerns erals. - the role of substances inhaled in association with the talc as the cause of the disease proc |R6rded for jmHicaboo April ?, I9SS. ess. Speculation has mainly concerned the f Dictor ;(ljr. Schepers) amf Chief Chemist effect of the quartz, which has frequently OjCr, Ptrk*)*Tbe Sanenae.Laboratory. . been demonstrable. On the other hand, cases m'* ''**''* V/ ,* Hi. *v*i. t- -- EFFECTS OF 1NHAU-D TALC-MINING DUST exist m which neither quartz nor talc have been demonstrable. Passing reference should also be made to the extensive literature on the granulomata associated with the surgical use of talc and the fact that tak lesions have been observed sot only in the lungs but also in the peri cardium, dse cpjcardium, and the gastric mucosa, besides surgical wounds. It is evi dent that a great deal may yet be added to die sum total of our current knowledge con cerning lids dust disease. With this object in mind, observations are presented in this paper on dust surveys conducted by The Saranac Laboratory of certain mines and mills of l!te talc industry of Northern New York Sate, together with the chemical find ings and histopathology of eight deceased em ployees from that same industry.* SURVEY OF DUST CONDITION IN CERTAIN MINES AND MILLS OF THE TREMOL2TE TALC IHRUSTSV OF NORTHERN NEW YORK The rock mined and milled in the area in Northern New York studied by The Sar anac Laboratory, although sold as talc, is a mixture of tak and tremoliie accompanied by a smaller amount of anthophyllite. All three minerals are silicates. The talc usually de velops in thin, flexible, white laminae that are characteristically greasy to the touch, but in some samples from this area it occurs in fins fibers instead of the usual plates. The tremolite and anthophyllite normally occur as coarse crystal grains, but in the area studied ?hete eases are part of a series collected by the late Dr. L U. Gardner. A manuscript under preparation by Dr. Gardner had not bees compkurf by the time of his death The present account is an independent study of the material without reference to this toaousertpt and elsewhere those minerals sometimes break up into long narrow fibers and then exhibit the structure and properties of as bestos. It should be pointed out that the term "asbestos'' docs not refer to one specific mineral but rather to any mineral capable of splitting into long, thin, flexible fibers and resistant to heat and chemical agents. Two distinct types of mineral are used commerci ally as asbestos: the bulk of the product is chrysotiie, which is a fibrous variety of the silicate mineral serpentine; the important remainder belongs to the group of silicates known as amphiboles and includes the var ieties amosite and croddolite, Tremolite and anthophyllite are also members of the arnphibole group. Since the experience in South Africa shows that at kast one of the asbestiform amphibofes--<rodck>ltte--is capable of causing typical asbestosis, there is reason to suspect that the fibrous amphiboles from the area studied by The Saranac Laboratory also might cause reaction of the asbestosis type. It is likewise possible that any portion of the talc which may be present in fibrous form might have a similar effect on tissue. Representative samples of the mine product from three mines and of ground tak from two mills in the area were analyzed by chemical, petrographic, and x-ray diffraction techniques. The results appear in Table 1. At the same time samples of air-borne dust were collected with an electrostatic precipi tator in two of these three mines, near a miner operating a jackhammer drill, and in the working area of both mills. Later preci pitator samples were collected in the third mine also. Analysis revealed that the dis tribution of minerals was somewhat different in the atmospheric samples (Table 2) than Tabu 1.--Compaction of Mine Product 9mA of Milled Tak from* Tremolite Tale Industry of Northern New York MIoi4 OjMtt.,...................................... UlMA, Fer Ctot MB* fntoet__________ msb* a. FtfOaU to to t S MtaC. ' FerOeot M a 7 6 s MflfcdTaM ' MUD, Fr Ceoi IS &5 to e t FUarJCBEen, t to u j e 3 Ci >012 D 93a tie aloe pnOatt e? Mines B aod C, tad Mm *opp!tid br Mb* 0. 181 SCHBPERS AND DURKAN TAjqji 2.~~Covtfiositicn of Atmospheric Dust Collected teilh Electrostatic Prfdpiioier i Mott* 0*4 Mills of Tremolite Tail Industry of Northern New York ___________ KWi* Miami PerCrte W W T*fc......................................... ................ .. .................................................................. AsWepbrBM.......................................... (&*......>............................ ................ U tt> l im i 2(0 le n AtiBetpberfepQtt KIm B. ftrCfgjt SS IS a t 60 UiMC, FWOcct ift 49 S t KfflD. Fer Cat S ii u 1 1 t K12IE, FKOat n to n i t u * Tbe tmo titspbe* of tawtrMiV dun from Kb* A vm Is dlffirtat fevKa ot tte bum. Tby n t***o evsn) sK^lAi |*wr thin iboie from Ktecs 8 *ad 0 Kffl* D *b<S fi. in the mine product and in milled talc. This distributed throughout the entire tremolitc finding U in agreement with previous ob- tak bed, but the analyses in Tabk 3 show serrations4 that the composition of air-boree that it can be present in substantial amount, dust may differ considerably from that oi Owing to erratic distribution, the quarts de* the source material from which the dust posits may be missed by random sampling, originated. Even in the same mine there 2a attempting to take cognisance o$ the may be substantial difference in the com* position of the air-borne dust: one atmosphene' sample collected in*Mine A had a potential pathogenic role which may be played by the quartz in the talc, sight must not be lost of the fact that the quartz found quartz content 'of 7%, while for another in the lungs of deceased miners who had also sample, taken at about thesame time but in worked in other industries may have been a [different level, the quartz value w^s only derived from exposures in those industries. 2Jo (Table 2). This variability in thequam content is illustrated again by comparing the chemical and rrraoaeArsic study of analyses o! various samples of rock, mineproduct, and air-boroe dust taken in Mine TSB lungs of eight deceased TALc-iNPVsm sh plovers A and in Mine B (Table 3). It will be The series of autopsy specimens studied noted that the per cent of quartz in the Mine consisted of the lungs of seven miners and A samples ranged from 21 % to $.$%, and in one miller from the tremolke ole industry, the Mine B samples from 41% to 9%. All the miners had been engaged in drilling ..Tins matter oS quartz content as men- rock for periods ranging from 10 months to tfooed in sbme detail; first,-because previous * 27 years. The mill worker (Case 3) had investigators1 have reported that they found been employed for six years, but, as his body only a,negligible amount,of quartz, ih sara-\ bad been exhumed for study 18 months plea of rock and of grotiwd arterial from- after Ws death, the findings are only of bro thisarea- second, because it has been deow. ited value. A portion of the autopsy ma- opstrated (T*b!c4) that at quarts ' serial was taken for gross specimens and for wai present m the hifigs of one'Riiner olidhistologic examination, and the balance was ODe-nufler from this lqcaljtyiustry who had V reserved for chemical, petrographic, and n other industrial `otposure to :dust, anti,.1 x-ray diffraction examination. For the coro- tfurd, because quartz is a known pulmonary; ponent chemical analysis and a lew oi the pathogen.'The quartz may not;be unifonnly . imneralogical analyses, samples of tissue * ** ; ' lUkLK 3,--Content of 'flock, of Mine Product, and of Atmospheric Dust from Mines A and B ....... m~ '--~ iiih~ uu.in " ii ii ii .................. .. ............ ............ in i ..... ..... in <. s <fc>ra KUtr A.rerOesi 8. Percent Bock _____ SUn< n4Mi .... 4taMpberfe dost' fc> Q Yt 20 .. is .. .. <1 .. 4s ........................ .. U t 1 9 .. .. .. to 17 9 .......................... EFFECTS OP INHALED TALC-MINING DUST Tasl* 4^-A*eJysis of Lungs of Industrial Workers RxpotrS to Dust & the TtenoUle Tele industry of Northern New York istopry Com Ho. nt ot en*e tu.. mhmm& Qesrtx........................................ ** ............................................. TtttteHtt................................... ........................... *Mep%t ..................................... MlsenUa fe&K............. ....................... **........... ................................. Tresc-UM ................................... PttD?K.......................... Cnsp^ocQU aw.;........... ................................. *&........<;................. **........ ... ............................... **>t............ S*>|........^.......................... . i*o .......................... VI- w^tad. - .................... & & % JIBO Best 2* % UAl UUr*l OetotfSoart* Fw OttT of Aik left SitM %* urn B7 Utt % TAB 0 t6 IS IB BHM U }u 6 Tr Xiaeral Oootlfnwota, IV Cent o< Drfctf TUra* SB * i 1 Tr & SB li 4 t % M t t 54 SB IB u BA U ej *1 .... SB 1,T o.s 04 tr CemoecBt Aaaiyaa, Ter Own ot as* sti < u IB UB fc< 20B U Al *u oj HJ SB tr U SB MB UB ai LLO *S <4 e.s 17 to U 16.0 SB OB OB OB 83 Tr .... m* SSB OB 24.2 JJS TB M ' SB 64 B.4 5?4 *.1* *0 tO UB SB AT SB SB U IB SB S.t w OJ OB SB n. SB SB DB SB SB no n 0.1 IB OB 04 sjb TB as UB SB SB SB SB were ^idVed from- representative portions 27 years' tafe mming exposure and 10 years' of the things and mixed. The samples were general ;tmning. then dfied ranight at 105 C and ashed,in a The associated exposures included service muffle Wumace, ^-Most of the mineralogies! as miners of zinc, lead, coal, and iron py determinations were based upon other mixed rites. This helps to elucidate the essential portions of tissue digested with 30% hydro talc reaction, as the normal result of exposure gen peroxide by the method of Sundius and to dust hazards in mines of the latter types is Bygdeo4 to avoid the alteration in mineral fairly well understood. structure sometimes caused by dry ashing. Our best fortune, however, for the present The results of the chemical and mineralogi purpose is Case 7, a person who had worked es! determinations are shown in Table 4. 23 years only as a talc miner before dying It should be pointed out that the values given . from an unrelated cause without any interfor sonie of the .minerals are only approxi- current..superimposed pulmonary disease, mate 4tiinates' xh*: quartz content was This case may therefore serve as a classical determined by a Special chemical and petro- exampk of a taJc miner pneumoconiosis, graphicj method! and is fairly accurate, but . Case'3. wtold have been equally valuable, the values in thg table for ta1c,; trenx&tc, and as this,worker had been exposed during his anthopJ^Hitc iftay be somewhat above or . six years_of employment as a surface crusher below the tru^vaUie, : .man and mHl.svnseper .fJnfominatdy, the l '* ' studies were nof*?ma<le;'tmtil his body was """WL-p*"* .awoaw. i8 ^oths itec hllrial ^ ^TH 3^?"ST mud, detail was pervert. However, it Thou; h our^ife of right cases appears confirms certain essential points. ' limited, we ;wer* .particularfy-Fortunate in . - ; having svaifabl^fa.study such a diversified JUNdawektal fulhoxarv -rate range of dust' exposures astd tang lesions . > ' *EACrWK . (Table )i'At the'One end of our scale we . The primary reaction present in Case 7 have Csi.l,*wrth1*ut:i0 months' exposure to consists of multiple irregularly shaped foci ale dusc. a mirrs^and 17 years' genera! (I to 3 mm. iq ^diameter) comprised of virmining. fathe dtfcfc&extremels Case 8, with . dually pure fibroeyrtc proliferation and macro- `'V'-'-" 183 u^ - - ; V,'J X >i* SCHBPEKS AND DVRKAN S.__Industrial Exposures, Cows of Death, etui Pulmonary Pathology Eight Deceased TrtmcUie Tk-t*diutty Employees Qac&'btam* ' T*it < Otter * Dettfe fttm ? Smaiso 30 *r. t Kao, CeJeoowo t-. Cauteoz Dtclfl Cot ?akooa*J Hat DrtOla* err. 14*4 mu* tfX. Iron b&> lit. w 46 CorpubRonide f tn. S*wptt i it, yb>e Drtniar urt. Vt*. CWBii* Ifljr, t s?< Um t OjT. KSJW f mi. tkeatet 46 TuteKtUesU ITT. CeaJatto* a Corpohaestlfe Ijr. 2rea nlM Syr. rjoemfc* a WMNSMl **r. Prnua Off. ti Beebrt&vttk eanl)o ltelojo ion. SH- OwjmOT* awtt t>rnw OosUaitft J9aimoo*rT laHona 'FBceDteosioUa JHbtOtefbUr. vfU> Wivunlu STtetalobttoUa fltofOttflalM SQfcotU Sd?*ecc4 AJffuM. teIoS'tue Bodglec Sl8uMtb tool! zwrotls tattedos *9 * 1 HlKoflofflioUi DfOote *uaxP3av ir mbuu>phmiitlir Kl CuloalB tober- ae&ultc WoiSfoCBl SJBUftO a&footJIaUr flOffwrltoltr K*Mle wuSwfit ad BHtiUtMftl OtfSaest oodekr Sbie&aar TotWTBlotffiMtto Cbroflie t>te*l tater* ubHUoUb Tuterculoiamiy vU&teitrtUi tTfolttteitMeuvllwtaKOeooBUs mw focal Dlffete flbrocefetter S3 vn KAfalrtnaJUtoeo! *a pipage accumulation. The cellular deport tends to be arranged in a stellate manner around medium-sired and smaller blood ves sel (Fig. \A). There is iairiy abundant visible pigment, which either is found within isolated komopberes or seems to lie in the interstices between the fibrocytes. Some of these particles are brilliantly birefriagest and may be present as spicules, some of which measure 0.5* by 5* (Fig. IB). Tbes* characteristic macules are easily dis tinguished from isolated mature silicotic nodules which are also present Some of the latter possess a halo of cellular elements and are probably composite tak and silicotic lesions (Kg. 45). Elongated terminally dubbed bodies, measuring 20* to 50* long and in no obvi ous respect distinguishable from asbestos bodies, are present in fair abundance (Fig. 7} mainly within alveoli, where they tend to occur in dusters held together by honio* phores (Fig. 8-4). A moderate number also occur among the fibrocytes, and in these sites where there are fewer dumbbell types, there are also more instances of degenerative changes. The intra-alveolar "talc bodies" are generally stained intensely by means of 184 Prussian blue, while those which lie among the fibrocytcs may be losing their iron-con taining sheaths as the Prussian blue reaction, is fainter and more widely dispersed. Many of the tooiophores io the alveoli show this blue staining too. The larger blood vessels trapped within these foci do not show much deviation from the normal It should be dearly appreciated that the focal lessons appear as isolated macotes io section only and really represent cellular sheaths accompanying the blood ves sels for variable distances. The smaller arterioles may show some endarteritis ob literans, and rarely a talc body may be found embedded in the vascular walls. The fibrocytic infiltrate abuts directly on the vascular adventitia.. However, these is no appreciable modification of die lamina elastic* oi the blood vessels. Capillary circulation through the fibrocytic masses is poorly developed. But little collagen , is laid down among these fibrocytes. The supporting stroma in stead consists of a delicate web of reticular fibers embracing groups <si fifetocyteA tativer than subtending individual cells (Fig. 2-d). Elastic tissue is absent from the centers of the cellular areas (Fig. 4-4). (i Fig. 1.--Primary lesion: tele mine dost exposort only. *d, perivascular cetfatar aggregation. 0, high-power-view, shoeing massed macrophage* and fibroeyies and talc-spicules. Fig. Z--Stroma d perivascular deposits of talcmts. A, reticulum supporting the macro phages and fibrocytes in the primary lesion, with talc components only (low quarts co'Ueot io Jong ash). B, collagen abundantly deposited with fewer cells (high quartz content iu lung ash). SCHEPR$ AND DVRKAN Fig. 3 --PeriraKviar fibrosis is taieosis, A, abundant fibrocelhiUr reaction around vessel (moderate quartz content tn lung ash). B, marked cottages deposition with paravascular oodute (high quartz content in long ash). Fig, 4.--Parenchyma] nodules faartd in takotk hmg, A, dominantly cellular nodule, with central amorphous change and talc bodies flow quartz content in hmg ash). B, hyalinietd wfcoried nodule, with peripheral ceftuter reaekw (high juartx content m hmg ash). EFFECTS OF INHALED TALC-MINING DUST At isolated, sites focal necrosis has super- . Lymphoid tissue is scantily present is the Vtsed within the cellular areas* There is no " hmgsj and the granulomatous reaction ap apparent zonul&tion around these necrotic- pears to avoid these fod almost completely, areas or any tendency to collagen deposition though-these granulomata may abut os such or caseation. No suggestion of tuberculosis lymphoid tissue. The hilar lymph nodes show exists, and the cause may be ischemic m vicyr hardly any hyperplasia and exhibit minimal of topographically evident arteriolar occlu pigmentation only. No talc bodies are to be sion or luminar carrowing. On the other found- However, minute circumscribed sili hand, tiie histological features are highly cotic nodules are present suggestive of histoplasmosis. Many of the bronchioles and some of the The perivascular fibrocytic deposits tend smaller bronchi are markedly distended and not to invade adjacent alveolar walls in mas distorted and are the seat of chronic inflam sive columns, though large numbers of alveo matory change without, however, any ma lar walls are moderately thickened owing to terial impairment of the epithelium (Fig. cellular m&trites, and this change is the SB). The latter indeed tends to be hyper* more evident at the points of junction of in trophic, with goblet cells predominating. The dividual septa. At isolated points the alveo- .bronchial glands are, also somewhat hyper- bjr walls $xt inclined to be tiun, but there is. 'plastic*. AJittk plasma cell infiltration into fijy a -slight tendency toward rupturing', as ; - the mocosk Is evident, but there U no collagen alveolarspaces are inclined to be moderately deposition. Tbe muscularis mucosae does not reduced in diameter. The resultant tendency aeon to be hypertrophic, because its c&* to atrophk emphysema is most distinct poneot columns are so widely separated. toward the lung periphery. However, this is illusory, and there is in Septal cells are not conspicuously devel reality fairly well-marked muscular hyper oped, and there is no evidence of macrophage or septal cell catarrh into the alveolar spaces. trophy. Sometimes this is focal In distribu tion (Fig. 9A). How effectively this muscu Virtually no excessive collagen is present lar system may operate is left in some doubt, within these alveolar walls, but a delicate in view of the patent invasion of the bron- chiolar adventitia by fibrocytes at many sites, reticular skeleton supports Its center. Elastic bundles are poorly represented and occur in as the peribronchial veins and arteries are similarly invested by the proliferating reac a fragmented fashion among the fibrocytes. Alveolar wall capillaries are occluded along. tion.* ' . *' somejaretehes where fihrocyte deposition i fconimn talc tarots particularly abundant, but more generally th? The basic lesion just described may be capiBary, circulation *s undisturbed. - recognised throughout this series of cases, though modified by the associated pathokigith'^Coinlutemrlnosbuolaf.rcseellputalartorethaectpiounlm; aocncoamryppaen-y1.' . cal processes induced by, other dusts. It is the moro remarkable to note that the cellular ripheiy, thus producing a.'coarsely webbed prob^eratiye^phendziwnoa is present even sebionaLaffeet.v There is ipore. coilageb in' in Case.$ where the history of talodust ex these septa than elsewhere (Fig-115). The posure is as streri as/lp months,,and persists pleura shows slight cellular infiltration and in virtually^simi&r fern not-only in Case ?> mild collagen > deposition internally to the with 8:history)of 23 years of talc exposure, kmina elasjka. 'Numerous talc bodies may but also in the instance of Case 8, where be' found-here, and some can be seen to par there' was a 27-year; talc-exposure history, tially penetrate the elastica. Superficial to .together withjlO years' exposure to*dusts the latter, a vascular rone of fibrbceliular rer.\ encountered in zinc and lead mining. action of variable thickness ts to be seenf . There'may a 'greater tendency toward Isolated silicotic nodules occur in this zone. the formation* of massive lesions and sub- It is covered by mesothelmm (Fig. 12), pleural reaction where there is an associated 187 w- -;;v .* ---- __ *i SCHEPERS AND DVHKAN fig. 5.--Parenchyma} cellular deposits in tale miners, A, loose cellular web, with atrophic . alveoli (moderate quartz content in lung ash). B, pigmented iron-staining stellate cellular deposit (moderate quartz content in lung ash). F*: 6.--Stromal reactions in talcosis. A, pigmented fibroeellulsf granulation tissue, with atrophic alveoli (moderate quartz content in lung asb), B, dense difiese fibrosis, with surviving elastic skeleton of occluded blood vessel (high quartz content in Itmg ash). EFFECTS OF INHALED TALC-MINING DVST fig 7,__"T*!cM bodies in human lung tissue. A. slender elongated "talc" iicdks embedded in fibrous tissue. B, short dumbbell body partly eogul/ed by a microphage and showing intense iron staining. Fig. B.-->Taic bodies in human lung tissue. A, accumulation o? koniophores, slm'hig a high degree of iron staining and containing short lengths of tak fibers. B, tak body among erythro cytes within the lumen of a blood vessel. V SCHBPBJtS AND DVRKAN quartz reaction. In Cases 2 ami 6, collagen dally, then, there are three cortical zones, formation>*5' restricted to a minimum and via, a fibrocelh&r internal component which the suppor^ng stroma tends to tj? of a retica- may be variably pigmented and which may lar nature of variable density. In Cases 2, contain distended bronchioles; as intermedi 5, aad 8, there h a greater tendency toward ate exaggerated lamina elastics, and an ex collagen formation. It U to fee noted that of ternal highly vascular hbtocelluUr layer usu these cases Cases 1 and 5 yielded a relatively ally covered by mesothelium (Fig. 128). high value for quartz in the lung* tissue hut The parenchymal stroma is considerably Case 8 showed a very low quarts level. Bire- exaggerated in (he presence of a quartz reac fringent quartz particles are a prominent fea tion superimposed c* the talc phenomenon ture of the tissues m Cases 1 and 5 and are (Fig. 5). This is largely a perivenous hot poorly demonstrable m other instances. change, and within these linear columns of The interstitial alveolar wall reaction is fibrosis partially or wholly occluded blood also more marked in the cases with heavy vessels may be seen, sometimes so effectively quartz-dust exposure, and there is consider incorporated within the scars as to be, be able collagen deposition even with some hya- trayed only by ihdr residual elastic tissue linization in Cases 1, 2, $, and 8. Indeed, in skeletons (Fig. 6), these cases the alveolar wall involvement is so pronounced as to overshadow -somewhat the essentially perivascular distribution, of the underlying talc reaction. , The damage sustained by the alveolar walls Vascular damage is indeed very much more in evidence io those cases with the long est history of feard-fk tninwg or whose the highest free-silica content was discovered. Two essential processes are present, namely, is further modified by the presence of quartz particles which ievolve marked macrophage and plasma tell infiltration, marked enlarge ment and proliferation of the superficial sep tal cells, often associated with cellular catarrh into the alveolar spaces, and finally moderate to marked, impairment of the capillary circu lation through these alveolar walls. The latter an endothelial proliferation in the least ves sels ending as endarteritis or endophfebics obliterans and a periartericJar fibrocytic pro liferation, with fib?otic structuring or partial invasion of the muscular coats (Figs. 28, 3B, 10, 11). This process is present in its most exaggerated form in Cases 1 and 6, in which multiple periarteriof&s gt*s\\daoa is not, however, a constant phenomenon, and may be found. - Such lesions cause marked there may he advanced alveolar wall disease pulmonary ischemia, the more so as the le without appreciable loss of capillaries (c. g,, sions ace not limited to the pulmonary cstcu- Case 6). larion but may also involve the bronchia! When collagen Is present, it fails to be vascular system at numerous points, thus arranged in the form of silicotic nodules m effectively precluding estaVftsbtnca? of any ail but rare locations (e. g,, Cases 2 and 5). collateral circulation. Incipient fibrous whorls arc present also in While ifee essential reaction to talc ap Cases 2and & Some He against blood vessels (Fig. $B), -It seems possible that the abun dantly cellular talc reaction is incompatible with the complete evolution of the nodular silkotie lesions, pears to include exaggerated distention of bronchioles and smaller bronchi, this change, though present in a variable degree in all cases of the present aeries, is not universally observed throughout the lungs where reac ' Subpleura! deposits follow the same pat tion to quartz dust is concurrently present. tern, being most marked where exposures to Instead, there is a tendency toward narrow both tak and quartz have been considerable. ing of the bronchia! lumen, epithelial desqua The resultant lesion is, however, an exag mation, mucosa! hypertrophy, sometimes geration of the primary tak reaction except with papilloma formation, and inflammatory for the greater prominence of the collagen infiltration, with adventitial fibrosis and where quartz is abundantly present, Essen- cicatrization at multiple sites where exposure 190 EFFECTS Of iNHALSD TALC-Mi}ITNG OUST Fi;, 9.--BrooduaJ damage in talcoris. si, irregular focal probferatioo of tnu$eulari tmicosae (low ocaru content in long ash), B. jubmacosal fibrosis, with lymphatic distention but no injury to (be epithelium (moderate quarts coatem is lung ash). Fig jo,__ Visedar damage in telcos!^ A, perivascular fibrosis and mtimaJ swelling (high quarts eoMent to Jnng shj. B% ttleoiie oodula to the walls of Wood veatels (low quart* eonlest in Itmg ash). SCHBPBKS Ah'D DVRKAH to quartz dust was adequate. Thi# combina tion of chronic hypertrophic bronchitis, oblit erative bfoaduolitis, and the peripheral bron- 5, 6, and 7. In Case 2 histoplasmosis is the obvious answer, while in Cases 4, 5, and 6 the lesions are more suggestive of tubercu- chioleetasia superimposed oa the SbrMe^ular losis or tuberculotiKcotls. There is seme* changes throughout the lungs may lead, on tendency toward inflammatory reaction at the the one hand, to extensive areas of partial periphery of the lesions in the Utter three attiectasia of the relevant lung fields or, os cases only. On the other hand, the necrosis the other, may be associated with the develop also involves the stroma! elements, favoring ment of multiple epithelium-lined peripheral histoplasmosis once more. In the majority of cysts. The latter are essentially baliooed-out other eases, it seems possible that the necrosis terminal segments of the respiratory passages may be explicable oq an ischemic basis, either and may be readily distinguished from em because the cellular hyperplasia had out physematous bullae by the presence of the stripped its vascular supply or because the epithelial lining, the residual basement mem latter had been cut off through regional vas brane, and the irregular presence of support cular occlusion. However, as all these cases ing muscle fibers. True emphysema is rela came from the St lawreoce Valley area at tively infrequently seen and, when present, the time of an epidemic in that region, it is consists 0$ the atrophic vesicular variety. possible that histoplasmosis may be a factor. The differential involvement of lympltold tissue in the reaction to talc dust and to talc dust combined with quarts dost is dearly demonstrated in the present series, Whereas the tak reaction tends sedulously to avoid the lymphoid tissue, the contrary condition pre vails when quartz is abundantly present or where there is an associated tuberculosis. Talc bodies are, however, never seen m the lymph nodes, and the reaction present in most instances is limited to medullary snacrophage infiltration and pigmentation. Silicotic or tubercttbiiUcotic nodules we present in but a few instances (Cases 1 and 5). Despite the fact that multiple nodules arid necrotic foci are present In the lung substance, the hilar node involvement is not marked. This state of affairs is the reverse of what prevails in the presence of exposure to quartz dust unaccompanied by an exposure to talc dust One is consequently inclined to infer that the simultaneous presence of talc dust and quartz dust in the lungs militates against the trans portation of the quartz dust to the hilar nodes. Alternately, though talc bodies afe not seen in the hilar nodes, their liberal transference is not yet precluded, and the inhibitory tendency of the talc on the silicotic reaction* which is manifest io the lung substance of this series, may prevail also in the lymphoid tissue. The process seen is Cases 4, 5, and fi, if tuberculous, has been modified considerably by the abundance of fibrous tissue and cells. A Urge thick-walled cavity, without a dis tinctive fibrous c&piuk or even components, is present la the latter instance. Atypical tubercles are present within this wall at the edge of the broad inflammatory zone. While tive temptation exists to interpret this cavity as tuberculous, it may represent merely a chronic discharging abscess. The lesion is also compatible with a diagnosis of histoplas mosis Attention may also be drawn to the marked peribronchitis and ulcerative bron chitis m the passage draining this cavity. No tubercles were observed here. Pneumonic areas were observed in the cases with exposures to both quartz dust and talc dust, especially Cases 2 and 4, but sot where only talc dust was the responsible etio logical agent This pneumonic process tends to show healing by organization in various stages of progression, and numerous talc bodies are thus trapped. It seems likely that those present in the formed lesions may have been incorporated in this manner through earlier episodes of inflammation. CQMttENt The chronic or long-term effects of the Necrotic foci were observed within the inhalation of dusts, such as are generated in areas <ii cellular proliferation in Cases 2, 4, tak industries, are thus demonstrated by this 392 EFFECTS OF m/r2.Z> TAl.C-mm*3G DUST V V Fig. Il.<--Vascular damage m takosis, A, progressive loss <rf vtsous Itssea through pro gressive proliferation of mtima (moderate quartz in long ash). B, fihroelastic scar in interlotailar aeptbm, representing the remains of obliterated Mood vessels (moderate quartz in lung ash). rie$ of cases to vary considerably according other industries to which the person may to the extent or nature of associated dust in have been exposed, either preceding or suc- Fig. 12^--Pleural damage jn talcosis. A, diffuse fibroceilfllar. partly pigmented, and highly vxscufar teawion (to** quattx conteM tog aah\. B, loose ptomwalien external to lamina elastics, with wboried nodule: tale plaque (high frweei!ica content of lung ash). I li . SCNEPERS AND DVRKA feeding Che period during which talc dust fi.es appreciably the type of reaction to ti breathed. quartz dust. Though considerable quantity . The hJtiopathological features enumerated of free silica were demonstrable in the Jur. are almost entirely explicable in terms of the tissue (Table 4) in some instances (Cases ! fnineralogical analyses of the lung ash pee* 2,4, 5, and6), thaw, xaswA to series seated in Table 4. clear-cut tendency to nodular silicosis. It is seen, for instance, that for both of our Tuberculosis or histoplasmosis may hav key cases of pure talc pneumoconiosis (Cases been a factor in the pneumoconiotie tcactio 3 and 7) the quarts content of the lung ash in some of these cases. White doubt persist (2.3% and 3.2%) was about the same as as to the diagnosis of a true infective process the corresponding value for many normal it does seem certain that if the latter diag persons never exposed industrially to quartz nosis has to be accepted the presence of th< dust. Among this scries, the amount of lung talc reaction induced an aberrant type o* ash of Case 7 is particularly low (4.69% of chronic inflammatory process. dried tissue), and so Is the total silica con- White it has been postulated that the fore tent (17.9% of ash) which includes the silks going observed deviations from the primary in the silicates present in these tissues. process may all be due to coincidental quartz Quartz was present in Cases 1, 2, 4, S, exposure to tuberculosis or histoplasmosis or and 6 ia concentrations compatible with to nonspecific pneumonia, reference should nodular silicosis. Indeed, the average quarts be made to the fact that there is insufficient content of the silicosis cases studied at The Saranac Laboratory is 9.3% of the lung ash. Cases I and 5, therefore, had unusually large knowledge in the present instances concern ing the differences in the talc dusts to which the men were exposed or to the concentra amounts of quartz dxaH lodged in their Vangs. tion and rate at which the tak dust was de Yet nodular silicosis was conspicuous by its posited in their lungs. The latter factors alone absence in Cases 2,4, and 6 and only sparsely are known to influence the nature of the sili present in Cases 1 and S. cotic reaction which may fellow exposure to Attention is drawn to the demonstrated quartz dust, and the precise composition of presence of tak, tremolite, and anthophylilte the tak may therefore necessarily be a factor in the lung ash of Case 7. There ia no appar too. Is this connection H is krtertsting to ent correlation in this series between the note that the majority of talc bodies were m length of exposure and the concentration of a range of 20#* to Sty*, bang somewhat longer these minerals in the lung ash. and thinner than the asbestos bodies generally The factor which seems most obviously to found in asbestosis. In rare instances some be responsible for the modification of . the slender fibers, measuring up to 200*, were essential reaction to tak dust is the abundant also present. Terminal clubbing was a factor amount of quartz dust coexistent with the tak in all but two cases (Cases 2 and 3), and in the pulmonary tissues. Five of the eight occasionally an intermediate bead could be deceased tak employees had been miners also seen. Segmented forms were but rarely seen. of lead, zinc, or pyrites. Attention is drawn In all cases the mantle of the body showed an to the minor differences in the mineral com intense iron-staining reaction, but degenera ponents of the lung ash. While wc do know tion of this coat was demonstrable in most that quartz is an active pulmonary pathogen, cases where the talc bodies were present in we do not yet know whether the additional the newly formed fibrocetlular tissue. substances demonstrated (e. g., feldspar) are capabk of playing a material role in modi fying the response to either the quarts or the talc or are themselves pathogenic. It does seem petmtaubk, however, to infer that the presence of talc dust in its turn modi- In addition to the talc bodies and the chemically demonstrable quartz, there were in most instances pigment granules and birefringent particles, spicules, and crystals within the interstitial tissues and in the konlophores. trapped within alveoli. The variable abundant 194 i EFFECTS OF INHALED TALC-MINING DUST presence of such elements at sites of maximal Vl A mineralogies! analysis of tbe lung fibroid or cellular reaction may undoubtedly from eight deceased talc-industry employ bear some relation to the differential patho revealed the presence of appreciable quan-V logical effects observed In the present series. titles of talc, tremolite, and anthophyUite. The pigmented particles, though present in Quartz was present in significant amounts ell tases, vert most abundant la Cases 1, 3, only ux the cases where the men had been 6, and 6, Brilliantly bieefdageat particles, cs additionally exposed to dust in mining indus the contrary, were conspicuous features tries other than in the talc industry. mainly In Cases 2, 3, 4, and 8, and in this The histological features suggest that series large numbers of such particles were tremolite may be the main pathogenic agent dispersed among the fibrccytes comprising in provoking the characteristic "talc" lung the pulmonary lesions. These particles were lesion. The role of talc and of anthophyUite identified aa talc. has not been wholly excluded. The "talc bodies" described may bean indi cation of the main pathogenic agent in the present series of cases or may be merely inci dental features. Were the former to be the case, it would perhaps be advisable to rename them "tremolite bodies." They were relatively sparsdy represented in Cases 3. 6, and 8, and it is interesting to find that in these very three cases the trernolite content of the lung ash was least They were present in greatest profusion in Cases 3,4, and 5, and once more the minerslogical analysis confirms the relatively high inci The presence of quartz modifies materially the nature of the "talc" reaction. The presence of "talc" dost ia the lungs modifies both the response to quartz dust and the course of associated infection. Marked pulmonary vascular damage was present in the cases where the quartz content of the lungs was highest, and this feature is in harmony with the tendency to cardiac deaths. Bronchitis, bronchiolitis obliterans, and broocftiolec&sisare associated major findings in this series. dence of trcmolite in these three cases {Table 4). The anthophyllite values, on the contrary, do not correspond with the hiatopathotogicaJ findings. It may therefore be The ehealcaJ analyses presented in Table 4 were aawfc by A 1. Redlin, chemist, Saranac LaboraUiry. R. S. T.menu 3d, PhD., of the U. S, Geological Surrey, formerly petrographer at The Saranac laboratory, made the petrographic and fairly safely inferred that Jhe "talc" bodies X-rey diffraction analyses. are o! tremoiite origin, la vkw of tiie fundamental similarity be tween the talc reaction seen in this series and the histopathologic*! changes present in asbestos's, one is constrained to speculate REFERENCES i. Sc&sd* R. 2, and Williams, C. J?.: Corn* mercUl Talc: Animal and Mineralogkal Studies, J, Induct Hyg. & Toxicol 24:75, 1942. Z Tberei, C: Die Specksieinlung, Beitr. path. whether the treraoHte component, being an Aaat t6:&5. 1896. as&esffform mineral, is not after all the main source of mischief. It remains for animal ex periments to shed some light on this subject, X /4ee| W, E, and Beaiwhkc, X- Pclmo&&ry Takosis with Involvemem of the Stomach a&d the Heart, A. M. A, Arch. Indust. Hyg. 5: i451, 1952. SUMMARY A survey of tl talc industry in Northern New York State revealed that the talc mined and processed there consists of a mixture of iak, tremohte, and anthophyUite. Quartz is also present m moderate amounts in the du$e generated in mining and processing the com 4. Hatch T., and Moke, C B.: Mineralogies! Composition ol Air-Borne Foundry Cost, }. Indust, Hyg. 4 rixicol. 18:91, 1936. 5. Siegai W.; Smith, A. R-, and Crrenburg, L.: Dust Hazard in Tremoiite Talc Miring. Including (Roentgenological Findings in Tale Workers, Xm. 3> Roentgenol, 49:11, 3943, 6. Stsrd/us, N, and Bygden, A.: Isolation of Mineral Dtfst ha Lungs and Sputum, J. Indust. Hyg, mercial talc. & Toxicol} :3Si 1938. j 195 . ;0~ [if I Ox imonarp in ~s$dl>e6to4 lA/or&er* XiKHTTM W. SMTTH M.fr, Kev ?s<i fibers can be found in paper, w&Mboard, 1HK iC-<v shingleA pipe covering, floor tiles, brake linings and brake blocks, cements, putties, Asbestosis has beesi described id detail in and plastics. numerous published articles and texts. While I It should be noted that the facts presented it is true that coses ol far-advanced asbesfeoris here apply to those persons who have been may have severe pulmonary disability, rela exposed only to asbestos fibers and to no tively fevj of the people exposed to the fiber other dusts. As previously indicated, industry develop the disease. Therefore, it is the today is finding many new uses for the fibers intern in this paper to mention asbestoses when they are mixed with other dusts, lx only briefly and then to outline various other is ac established fact that when asbestos putawnary disabilities sees among asbestos fibers art mixed with silica, diatomaceous workers. 4rtb, or other potentially toxic dusts, the The word "asbestos" is generally used to describe several fibrous magnesium silicates which are different in their chemksl compo sition and physical properties. The most important types of fibers are chry$ottte amosite, crocidolite, atwhopbylirtt, aerinoliie, and tremoUte, Total world production of an fibers last year amounted to slightly owre than 2,500,000 tons. Approximately 9Sf& of tbs fibers produced were i the chrysotfie pulmonary changes resulting from die mha* Urios of these mixtures are not typical of asbestosisJTbe x-ray pattern may be differ ent, the caeicaJ course changed, or the sus ceptibility to imercurrent infection increased or decreased Thus, in making a diagnosis of occupational pulmonary disease, it Is highly important to obtain a detailed occupa tions! history, so that asbestosis, silicosis, or mixed pneumoconioses car. be differentiated. variety, 5% erocidoiitc, and 2% amosite. The statements and observations repotted Deposits of various types of this mineral are here concern several thousand men and found in many countries, but the largest * women employed in the asbestos industry mines are located m Canada and Africa. in Canada and the United States. In this Asbestos fibers ate highly resistant to heat industry the various mining, milling, and and adds. They have great tensile strength manufacturing operations create some dust and large surface areas. Because of these containing asbestos fibers. If the fibers up to properties as well as their filameoted struct SCV in length are inhaled continually in twe, industrial use of these fibers through sufficient quantities over a period of several out the world is increasing. The textile in years, a typksi pulmonary fibrosis will dustry feas used them for many years to - develop. It has been demonstrated that this produce blankets, clothing, threads, topes, fibrosis is due not to the chemical but rather tapes, braided tubing, and filters. In recent to the mechanical action of the fibers.* The years, however, there has been an increasing asbestos fibers are deposited in the terminal use oi asbestos in the insulation, building, bronchioles* initiating a tissue response which and friction-material trades. In addition, the coats the fiber and eventually produces what Is known as the asbestos body. This appear* Seconded for publication April 7. 1955. to be a defense mechanism o! the lung, Na Medical Director, Johns-Ma*v<Uk Corporation. merous asbestos bodies can be found in the 196 81 .< PVIMOHAKY DISABILITY IN ASBESTOS WORKERS sputum of persons who have had only short aid sporadic exposure to the dust. These persons are healthy and have do demonstra ble signs or symptoms of asbestosis. There fore, it seems more appropriate to use the term `'asbestos" bodies rather than "asbeslosis" bodies, signifying exposure to the 6hers but not necessarily indicating disease. If increasing quantities of the fibers are contSmsfly inhaled, the tissue reaction pro gresses, and a generalized, diffuse fibrosis gradually appears throughout the lower lobes of the lungs. With additional exposure, this______ m- 'M! <;v* - m *ag. fcj-8- rt-*; r*. V;.'.' ' :%y^. * r** * * . w$$ Fig. Z--Moderately advanced asbestosis. may account for the "ground glass" pattern which has been used to describe the typkal x-ray picture. In moderately advanced, or second-stage, asbestosis (Fig. 2), the infiltration has in creased but still is confined to the lower Jung fields. The "ground glass" pattern is Fig. --Far-advanced asbestosis. Fig. I,--Early ash&slosis. fibrosis will spread to the other lobes, even tually causing respiratory embarrassment and finally cardiac failure. The pulmonary fibrosis resulting from prolonged inhalation of asbestos fibers will produce a typical x-ray pattern. In early, or first-stage, asbestosis (Fig. 1), the x-ray shows a fine, diffuse, homogeneous infiltra tion throughout both lower lung fields. It should be noted that this infiltration is bi lateral, that it ts generalized at both bases, and that the nodular conglomerate patterns of other pneumoconioses, such as silicosis, are no? seen in asbestosis. There ic a mn- reaction assocs- r: rrs*4 197 S '* -A4NES '* {y . SMITH \s-* mdre apparent, and the heart borders are Gregoire* has reported that pulmonary tixommg indistinct or shaggy. There is some lunetkm studies on asbestos workers have ./irregularity of the diaphragmstic outlines shown that the chief physiological problem and beginning obliteration of both the csrdio- is that of a "tight" lung. The vital and phrenic and the costophrenic angles. maximum breathing capacities are lowered, Is far-advanced, or third-stage, asbestosis expansion of the lung is difficult, and arterial (Fig. 3}, the infilmisoa still homogeneous oxygen satw&tvafi of the H006 is diminished and bilateral, has spread to the middle and in some cases, indicating an impairment of possibly the upper portion of the lung fields, gas transfer through the Jung. Diffuse ob but the apices remain clear. The cardiac out structive emphysema, so commonly seen in line is almost completely obliterated, as are silicosis, is not apparent in asbestosis. These the domes of the diaphragm and the costo- pulmonary function studies are of importance phrenic sulci. With this picture in mind, it in the proper diagnosis of pulmonary fibrosis Is advisable to reiterate the observations of and the estimation of pulmonary disability. many physiewms, namely, that the x-ray pic Oi more importance is the fact that these ture should never be used to estimate the tests can often help the clinician in directing presence or the extent of impaired pulmonary the treatment of the case. Unfortunately, function or disability. Many cases with x-ray there are too few persons who are properly evidence of third-stage asbestosi* have been qualified today to carry out these tests and known to carry on their usual work and *ra interpret the results. fairly comfortable .lives for several years. An x-ray survey was made of one group On.the other hand, no esse of definite disa of 708 employees working in an asbestos bility has been seen unless there was the mil! where the ore was dried, crushed, sep- typical x-ray pattern. srated and graded, packed, and then shipped* There is no typical clinical picture Cor Operations in this plant required the em asbestosis. The disease is insidious in its ployees to route through various jobs; onset and slowly progressive with continued hence it was impossible to relate any x-ray 4 mhaU'.km of the fiber. 'there is a gradual changes to * particular Job or to a specified increase in cough and expectoration, some dust concentration. At the same time it could anorexia and weight loss, then slowly in be assumed that all members of the group creasing dyspnea. Cyanosis and dubbing of had been exposed to varying concentrations the fingers are rare fadings. There evi of the dust. The chest x-rays of these em dence that asbestos w&l not progress after ployees were divided two three broad exposure ceases, but it$ seems to be true groups: (a) essentially normal lungs; only if the worker docs not develop an inter-} (b) marked linear exaggeration (P-2) but ^ current pulmonary infection. no typical pattern of asbestosis, and (e) def it will be shows that asbestos workers are inite asbestosis. {mot predisposed to develop more intereunrent Tabic 1 shows that of the 708 employees pulmonary infections than aretoundin other studied 649, or 91 %, had normal x-rays. workers. However,! when an acute pneu- ITiis is of Interest because 204 employees, or tnonius develops in the presence of an estab #9* oi the total group, bad 10 or more years lished asbestotic fibrosis, the infection is of service, and 2 men actually had worked slow to heal, relapses are frequent, and the more than 40 years in the dust. [. patient', may be more. susceptible to subse Table 2 Indicates that 52 of the 708 em quent pulmonary inlections. While it is ployees showed a marked increase of all peri true* that.the disease U slow and fnsidiows r.. onset and.that people with advanced ,;..asbobsis.m*y lead relatively normal lives, :Sfenida% the heart begins*lp fa}!, and death bronchial markings, although none had deh- * Gref-oire, F,: Pulmonary Function Studies in Men kw Ten Vears to Inhalation of Asbestos Fibers, rd before the Seventh Sara nac Symposium. J9S2 (wpub)isM}. PULMONARY DISABILITY M ASBESTOS WORKERS Table Is--Emflcy*t4 with NemeJ X-Rayt r ( V ........................................... H M &44 u.| *41 MMABO.............................,........................... tat 1& H *6 4* U K4i IMS t4* $I1 4*40 1\ cite asbestosis. Inasmuch as the majority trades. The Colbwing survey was made m of these men had essentially normal x-ray order to determine the incidence of non- films early in their employment history, it ccupatiooal respiratory disease in another is assumed that most of the later increased group, of 1561 men and women, working 'lung* markings were associated with their In the asbestos industry. subsequent dust exposures. Farther indica A c*9ie*rofabsenteerecord indicatedthat tion of the length of exposure necessary to no valid conclusions could be obtained iron) develop x-ray changes is seen when it is this source, because the reason for rbsence noted that of this group had 10 or was give by the employee himself. Sickness more years of exposure. often was used as an excuse to cover short Table 3 shows that of the 708 employees absences Cor a variety of personal reasons. 7 had developed definite x-ray evidence of It then was decided to study the claims aslxstosis. These men exhibited various submitted for sickness and accident insur stages of pulmonary involvement, but all ance. AH employees m the survey participated were working steadily at their accustomed in a plats operated by an independent utsuc- vdth no signs of *disabi!ity. It is of *ancc ^company,. lademnifiratioo^was made mteresi to note that none bad -dewtoped only after the nature of the illness had been x-ray evidence of asbestosis. with less than " certified by the treating physician. 2G years of exposure. The study included claims submitted over 'll Frequently it has been stated that it takes a three-year period for such illnesses as the from j to 10 years of exposure to develop common cold, sinusitis, pharyngitis, grippe, - asbestosis. The survey reported here coti- bronchitis, pneumonia, asthma, and pleurisy. . sr.mt& mill employees. It is possible that Occupational respiratory diseases and pul . other operations might have different expo- monary tuberculosis were excluded m the - sures with other disease experience. Factors report. . which might influence this experience are not Tabic 4 shows that of the 1561 employees v only the, kugth of exposure or the concen- in the survey group there were approxi , fretibn of dust in the air 6uf afao the fact mately equal numbers in dusty and nendusty that there is probably an individual suscep- occupations. Of all claims filed for respira- tifeilifyTo the^eveTopment oTpufmonary--tory diseases, 45% were for employees with fibrosis. Medical literature has given considerable attention to occupational pulmonary disease, but very little has been reported on the oc currence of nonoccupational respiratory dis dust exposure, Oinkal observations for many years had given the impression that a dusty occupation in itself would not predispose a person to more noncccupational respiratory disease than4 would a dust-free job. This ease among those employed in the dusty survey shows that the rate of disease over .v-^---- kpomat, jt. Table Z.--Emplcyw with P-2 X^Ray Readings 14 M yyU 5 U t ' 19 f U{ 804* 44 4H 1 1OI Table 3.--Employee* tw'Jfc Aj&rtaAi ftriww*, J-*............ s, ........... .......... ........................ U ............o '*>1. toil Ifesi j &S8 304* e-j i* i I-' 6 40-tt 4HS 5 SUtTH a.,*tbree-year period was approximately life i&m* ic the two groups. In addition, there . 'was no appreciable difference in the duration of illness in either group. Animal experiments and clinical observetkmj have shown that asbestosis does cot predispose a person to the development of pulmonary tuberculosis, cor does it aggra vate an apparently healed tuberculous lesion. In two isolated ooe-ifidustry towns m the Province of Quebec where asbestos was mined &ad processed, the incidence of tuber culosis over a period of many years was so greater than to other isolated towns with comparable populations but without a dusty F*. S.--Eketron mierograph, amorite asbes\cx; x SOW. than that among the general population of these mining towns, P Conflicting opinions and different reports intake it extremely difficult to confirm or deny conclusively the causal relationship of asbestosis and carcinoma of the lung.-Too often a common conclusion is drawn from observations and experiences with different racial groups, living in different parts of the world under variable socioeconomic condi tions and working in diverse occupational exposures. To these variables should be padded the fact that there are various types Fig. *--Electros aticrograph, chrysotile asbes- of asbestos fibers. t*, X. Fig. 6--Electron micrograph* staddolite asbes traded In addition, the incidence of tuber tos; X 4000. culosis among asbestos workers was lower P. *. Personal ecemnunkatron to she s 4,--SenoccupaUonal Disease Experience er**, totaJ bo................................ rati atorea *iu* *un expose*.................... 80? ^forces Mtb aoduss expoe&n....................... tu tea for mpluto?? dletue..................... r? 2bnhr*tor raptnlor? <tlMM MiB Oat u> u tires tor mplnbiTj dJatost MU a dust *Xure ..................................................................... .. Vi Arena* koatfe t ibtme mu than ex {XWu*,**............................... . ts Avtrogt kueU of MUj to dust enet*. *t............ ....................... 8.1 FT*i PULMONARY DISABILITY IN ASBESTOS WORKERS Vr, - BadoBet J has reported that there are Physiologically, asbestosis is the problem several differeat types of asbestos fibers used of the "tight" lung. Expansion of the lung by industry today, and these fibers have is difficult, and there is unpaired gas trans different physical and chemkal properties. fer through tiie lung. Diffuse, obstructive Figures 4, S, and 6 are enlarged electron emphysema is sot common. micrographs of three types of fibers used There is a typical x-raypattern which can most commonly in industrial processes. The not be confused with other pneumoconioses. k>ng, soft, and silky chrysotile fibers are found chiefly in Canada, while the amosite and crocidoiite fibers which are shorter, stiffer, and brittler come from Africa. Canadian experience with asbestosis has been limited to the chrysotile fiber. The ma jority of industrial processes in the United States use this fiber, but in recent years there u increased use of the amosite and croddoHte fibers. The British and European industries use greater quantities of these harsher fibers. Therefore, in trying to clarify die causal relationship of asbestosis and bronchogenic . carcinoma, many variable facts should be dearly identified, especially the type of fiber used and whether or cot other dusts were present in the industrial and environmental atmosphere. summary Respiratory disease experience among several thousand male and female asbestos workers in the United States and Canada u reported. Of all workers exposed to the fibers, very few develop asbestosis. Asbestosis is insidious in onset and pro gresses slowly with continued exposure, causing respiratory embarrassment and car diac failure. An x-ray survey of 708 employees in a milling operation showed that the majority lad normal x-ray patterns, that 10 or more years of exposure were necessary to pro duce x-ray changes, and that no cases of asbestosis were found who had worked less than 20 years in the dust. - The incidence of nonoccupatfonal respira tory disease was not increased, nor was the illness more prolonged among workers ex posed to asbestos dost than among nonexposed workers. Asbestosis does not predispose to the development of tuberculosis, nor does it aggravate an apparently healed lesion. There are several reasons for different opinions expressed concerning the relation ship of asbestosis and bronchogenic carci noma. Differences in asbestos fibers are noted. REFERENCES 1, VorwaJd, A. J.j Barkan, T. M, and Pratt, P. C.: Experimental Stages of Asbestosis, A. W. A Arch. ladast H*g. $:1-43 (J*n-) 1951. Z Badcltet, M. S.: Asbestos: A Mineral of Unparalleled Properties, Gutad Min. & Metal April, 1951. 3. Badolkt, U. S.: Asbestos Fibers: Produc {References 2 and 3, tion and Usage, Canad Min. & Metal. Aug., 1953. 2)1 t onartf CoJWli intnp 3. Geology- The geology is important, as die mines with thin coal seams necessitate a J.W.& HANNON, M, Wte. considerable amount of roof drilling, causing dustiness of high silica content. Faulting of the coal scam by siliceous rock also requires In the study of pulmonary disability asso ciated with coal mining, one must of necessity give due consideration to the etiological fac drilling of this rock, and the. tt&eeqwm pro duction of high concentrations of silica dust. The geology can vary greatly from mine to tors that produce abnormal pulmonary con Sw the same gtnen>S axes., ditions in this industry. These abnormalities 4. Type of work. The specific job of the are both anatomical and physiological. The miner has a definite bearing on his exposure. ttvnn&g of coal produces dusts th4t Vary tarf Men engaged ta rock drilling are exposed to relatively pure carbonaceous 'material, on the hig?) concentrations of silica dost and a small one hand* to rebtiyely^puri siGca, On the amount of coal dust. Coal-face workers are other, with a mixture of coaVand siti in exposed to relatively pure concentrations of between. Because of the many fluctuations coal dust and develop characteristic lung that can occur in the aerial dusts of the work- . changes. Coal trimmers1 who load ships at ing atmosphere, the pathological changes in the dock are also exposed to coal dusts and the lungs assume many and bizarre patterns, develop the same lesions as coal-faee workers. The quality and the quantity of the dust pro- The tendency of some coal miners to move duced can differ from mice to mine in the from mine to mine, with the associated same genera! area,*from job tojob in the same changes in job types, production methods, mine, and even from man to manioc thesame dust control, and geology, U of etiological job. These variations can be accounted fqr by . significance. A complicated and somewhat the following factors. .; -confusing environment can produce an in- 1. Production*B*tfds. The' type of pro- pathological pattern la the poeumo- duction methods has a definite influence a.. coc'0$IS associated with coal mining. the amount of dust produced. Mechanical The industrial pulmonary conditions found mining-produces more dust and smaller par- in <** mining can be grouped into the fol licle.sireMban hand methods.... . .. _ ^tving etiological classifications: , 2. Dust control. The high incidence of coal miners' pneumoconiosis in Welsh pits is best explained try the introduction of mechaniza- dust--silicosis uix* dusts-^athmoaiicosh ^ dwt-^thracosis; emphysema tioa without adequate dwt suppression. The Any of the above forms may be modified patchiness of the incidence in the United by infection or overwhelming concentrations Kingdom is best explained by differences in of the particular dust to produce progressive dust conceitrations- massive fibrosis. Recorded for publication jiine 6, 1955. Medical Cttreclor, h$clmyre Research Foundstk 202 SILICOSIS Classical silicosis can be Sound in coal miners, and its clinical course does not differ ffipjo *wptPK > l*PS 4*PA\ `2oipe^ jo iuUQAdQ *q2BO) <Mqf J<Md Xewanos iiodsp opoosjqun pajiamStd SuiAoqs '8un| jo oajpM 'g *st**jqu Jtpipoa {mpiiqtitaqp.* fotdXj 30 /*i-x V--7 -JJ3M 9Aq 0q* wsp UJ XjUO Wq fiO^JOAV pOO jp ui jnoso jou soop ij ajnsodxo jo qiSuoj sip pue isnp poo |o suopsjiaaouoo sqj 01 uoryodojd jj$p m w X)U*a pus waap -raoi S3* pos 'sooB3t|jnB jo uopsoqduioo s s* jno ud (j Sig) mussiCq<Ju jeoojuod VK2SAHJK3 Xji|iqwip jo sLiis^qoid juaraid Xjpnsa jou soop 'sonssij iCimtouqnd aip jo duquouiSid joontcwqns pus uopuojM oqj 01 anp s3urq sqi jo uojjipuco 5 `(j 2?d) sisoawifjuv SISOOVSBiHV '^jo.v. ioj Xiioedeo pouassa; e put `anSpsj <3oqo aqi ur ssatnqdri `qSnoo `eoudsXp Supnpoid jo afqsdso s* 31 saSsja poousAps aqi ui pus XjfjSAOi jo saS*?s Xusuj m sanooo sisooqjS soujsnpui iaqv> ui puooj jsqi Uioij XjoiEJsvsBq 3eu&is$ "<i'K >9<feqas *11 *M 0 *n(odp saojti^tr* atp 0} uoqt|i m eueq<fura joojjrtd put tcu[BAajd gpta wt sajnpou aqn rtM o> oop -epj ts sinax> gtuasXqdw jb|mca fsipipou opo -tiipus xtuastaoo put sretwijts y> rainpon pjioif* 4jt;nOJU SauMAft 'aha ja<4*a0( Isiwsiipire q](A ijsoMjis `g 'tuta^Xyduja poojuad usvdpus tpuo n{so<bp moxreBoqiso ijejjsw SiqAoqs `asu JOAod ao; !s;coijrt tnoqtM spoa&npus 'y--^\ 'sisootjts wnd oj isinms ajnaoid jetuip * sootipoid sreooqfsoosiqiuy ssidA oka io q sand XjMpsiw 03 poo and XpApspj uuwj pSirap ms sojnsodxo sqj 3i3qM joqjoue 03 qol uo ujojj Sauoiu Xq 10 jsnp paxuix b oj 3insod*o Xq popsjjBoo sj jj 'sjouiiu poo dooms sjrooo tpiqM uorjip -uo3 9 soquosop Xjajsjnoo? pns Xpjsnbape aim oqi jetp OAO*pq sjoqjo sjrq* (/so -qiscoBJ^ue,, aun oqj pjewip pptoj oqM mos 3J? wsqx dumiu: poo ui jnoo soop srsooqrs pyrpoia e sn waqjo Xq pms sisomoo -ornnoud paxnu rt qsijug otp Xq 03 pouaj pi uoprpuao e '({ *3i,f) sisooipsooaiqjuv SlSOOniSCOVSBiM v QNiNM ivoo hi Aimaysia AXVHOvan* 3Z *Xjoqrr aeow* -rTw h&Ava* *AV *0 *wb<0 pofde ^stwn epi* `sssnt *3 qfexuin iawpst s?te*n 'a *%UBS^duza jmq Xfomradaita ep<a 'fitojqg jrd `Mfsseuf jvAitgq jo &i-x' Ajuopejsfiss nq X 3on ssq sun^ ,sj9U}aj jeco u; t^sarqy Mrmco jo X^oys jx ns^aid sajssvj* 3Aissa*oca.i {SOlSOjOqied JO JflBOUJS *qj oj.jebcJpj<I ogi3 jo Xtytcpirp pue ewdsXp osnto ok> efcXqdu uot&fujsqo fSKiWpiSTre ys neqj jotpej >Sireip .*> rtxxi& ipyfi aaftopaicn pniojpsnj ai j^nsQj suotiipuco &qx '*** pwtdsw sq* jo juajuoo opSXxo aqj duj^npp pas XjpopA aq* fetsswodp Xq se ]|9A ss sSunj aqj in jp? l^npjsaj turssaioin Xq Xjijtqsstp sasnea surasXqdu#vesojua5 s&foapaojq Xw^ewdsaj aqi p aot^^rp pas^isui p Xftepoassa Supsisnco s* raresXqdu joojusd paquosap seq , uowfddafj t*sajonpof>*t XjQjiidsaj . p panoj* BQfjaapj pjo p vs*** padojdAap -v-; >y !tll >5ws-'g *nsXqta fsaia psi*porepc* epdaenduv SuMoqs jeaojirtd ptoOSApe qiiA 'rjsOJWtpa* p.Xu-x 'p--p -Stj ` .Sir li^'N. * "*' ,%< ATCMW# Stz 6--iN. kfc'kSfo* aS,>.#3i &*#**'& ?V ". 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OSMON&, MJ> H*, U. THE PWST HAZARD . la the foundry described large castings in the range of % ton to 350 tons are manufac tured. Because of a multiplicity of mechanical factors, involved in the process of cleaning .castings, the silicosis hazard in a foundry increases proportionally with the size of the castings, The present foundry provided no exception to this rtde. ^Repealed appraisals * of, the dust in the plant made by competent engineers revealed a material and continuing dust Itazanl The company introduced every recommended or possible hygienic measure butfailed to bring the hazard under complete control. Realizing that it was not possible to prevent entirely the release of quartz and cristobaJite dust, the company instructed me to study-the aluminum method of prophy laxis. This was done over a period of four years in an adjoining silica-brick manufac turing plant. The observations derived from this study wtee sufficiently favorable to de cide the company to apply the method to its foundry in 1948. At the time of introduction of the aluminum method dust counts con tinued to be higher than desirable. The dust concentrations and the percent age of free silica in the dust varied from job to job and from man to man on the same job, especially in the case of the larger castings. Because of the inability to clean tlie larger castings'prior to the chipping operation, die ehippers received the highest exposures. The large castings, which sometimes took weeks Recorded for pablication July 5, 1955, Medical Consultant, Mesta Machine Company. to cool after being poured, showed a con siderable amount of conversion erf the quart zite sand particles to cristobaJite. According to Hannon,1 cristobaKte tends to fracture into extremely small particles when sub jected to shock owing to a difference m the moleeular structure. * : THE SILICOSIS PROBLEM X have been continuously associated with this company for 19 years. The men who developed silicosis were do! different from men in other plants, and silicosis occurred in many stages of severity. Nany of these cases were of simple silicosis and detectable by x-ray only. The silicosis was classified as severe when there were associated symptoms of shortness of breath, tightness in the chest, weakness, cough, and a decrease in the pul monary reserve. Hie feet that these were casesa/genuine rilicoris rather than sidwosis was confirmed by periodic x-ray and spo radic autopsy studies. The pathological picture of silicons was found to be sot unlike the classical silicosis found in comparable steel plants which man ufacture large castings. The roentgaiographie findings have like wise conformed to silicosis in other steel foundries. The time required for the develop ment of radiologically detectable silicosis varied considerably. The rate of progression of the disease also varied, but in most cases progression to the advanced stages was found to be relative^ slow. The earliest roent- genographlc signs included linear thickening of major and minor lung markings, a wide spread small oodulation without preceding changes, and focal modulation usually con fined to about ithe midupper lobe region on OSMOND Is the established case of foundry silicosis the nodular pattern with aad withcan areas of "pockmarkiog," as described by Cole,* was by far the coEranootst lesion. Conglom erate reactions, almost entirely confined to the uppet k>bc regions, were late msniista tions, Emphysema in varying degrees was a constant accompanhncat of the sibcotk proc ess. When this foundry was first studied, in 1936, there was a high tuberculosis rate among the silicotics. The rate has fallen off remarkably, and only one active case was found in the past three years. During the latter years there have, however, been a iarr number of cases in which radiological lesions, thought to bo tuberculous, developed in the interim, with regression, scarring, and staMlity. AUmiKUK fRO?HtAXlS *NO TMA-raSKT either fhe right or the left side but more commonly on the right. Some cases devel oped massive conglomeration without much or any apparent piseeding wadvdation. In order to evaluate the effect of aluminum prophylaxis and tliwapy on silicosis in tbis foundry, chants in the pulmonary function were used as the essentia] criterion. Cjgcizanee was also taken of the x-ray changes and physical condition o! the men. The men Fig. 2.---Diagram showing manner of action of aluminum powder mill: (A) air inlet; (&) shaft; (Q.shait block; (D) sound insulation housing; (E) ball mill; (F) air inlets to mill; {G} air exits from mill to null shaft; (if) aluminum ptllev4; (K) jt5 bearings; (1) inlet to bottle; (M) bottle; (A1) one-way breathing valve, and (0) breathing valve orifice. 22i` 1 i i CONTkOL OF SILICOSIS were divided into three groups, namely, the choppers, the xnolders, and the miscellaneous employees, respectively. There was a total of 62 dappers, 39 molders, and 188 in the mbcrilaneons group, AJamSstna w adm&stcred In the fottowiag way. A mall McIntyre aluminum mill (Figs. I and 2), whlcbprodcccd 32 mg. of pulverized aluminum per Rttr of air at an air flow of 10 liters per minute, was mol Owing to imjngeanent in tbe **d=S flask, breathing tabes, and breathing valve, the amount of powder rdeased for tnspiraticaa was redaesd to approximately 50% of tbe amount generated at tbe mill outlet Two men received treatment tinmhaoeoosly, as shown in Figore 3. Kach cneh employee received on an average 230 minutes' inhalation therapy each year in the form of weekly sessions, lasting an average of S mutates each. This ateuinam regimes was varied is propor tion to the estimated severity of the qoartx exposure to which the men had bees subjected previously and to which they still were exposed Tbe pulmonary function was determined by using the criteria listed below and evaluated with refer ence to standard normals established in the Uteratare. In this connection, the observation may he made that standards of normality vary considerably between different laboratories, and average values published by separate investigators were relied on. The following were the criteria on which most reliance was placed: Fig. 3.--Demonstrating manner of administering aluminum powder. 10% deteriorated further despite aluminum therapy. The balance of these men (89$) showed a remarkable degree of improvement. Indeed the lung function figures obtained in Ortewfs novmftl&ajacv Vital capMftr. a*. ................................... CD. 8. A. x *<ta x Imt*!) Kasteit bnataUtt ecpadtr, Uteri.........US-MO&ttf* . HtxUDd tidal rotoaw, <*. ....................... iMOfttX latt) ?u!EBMsrr reserve, ec.............................330(0 x (asd4e)) RESULTS The status of the men during 1954 is com pared with their condition during 1948 and is sumrftatlied in Tables 1 to 4. The result obtained with respect to the chippers is most remarkable, having regard to the fact that their lesions were more ad vanced and that they continued to receive the same significant degree of dust exposure. It will be observed that only about 9% of these men who commenced the aluminum therapy is 1948 with a normal functional reserve showed any deterioration by the end of 1954. , Of those chippers who were functionally unpaired at the commencement of their period of treatment during 1948, only about i 78*fo of the cases could be classified as nor mal (Table I). The dust hazard--and the consequent severity of the disease--was next highest in ?a*le Is--Charts in the Functional Lung CafocUy cf Foundry Chipfrrt (Sixty-Two Work men) Subjected to Period oj Aluminum , Theropy-lW-1951 f Ts*r JfcS*........................ IMS..................... MW.......... .. ............ lAXR# ?UUr> ItOU Status Xonatl / CsstUred \ ow fciboonatsJ f Unaltered ( Improved Sfeo,*. t* n i 8 St Of Um 16 who faprowd, S3, w-esv com*! st lb* tin* at the period et mhusmii to 18S<. OSMOND Tabic 2t--Cha*get t* the Functional Lung Capoc* %ty of Foundry Holders (Thirty-Nine Workmen) Subjected to Period of Ahrmnum Therapy--1948-19S4 IMr SMS.., IBM.... fr.. Lot* Fan* ttoSlAtU* Mtf.Ho. Xomi] / \ Attnvkted u 93 8 Sutaorsoa* li f tTnrJiMWS 1 rtrrrHnttteO 1 2opro*d * \ 8 St * 0* tl*e H aho taprerd. 11 am Knetl at toe tlae f teal rmrimiT a 1*U. aluminum therapy with demonstrable func tional impairment, 7% showed no favorable response and became aggravated. The bal ance (93%), however, improved, and of this group 78% reached normality at the end of the six-year period (Table 3). The totals for the three groups, namely, chlppers, molders, and miscellaneous em ployees, are shown in Table 4. X-Ray Studies. -- Roentgen-ray studies were made on each employee studied in this series at periodic intervals, and each em the rnolders, and the results obtained with these men after six years of aluminum ther apy consequently also appear to be signif icant. Of those that started off normal in ployee was x-rayed at least once each year. It may be significant that during 1953 and 1954 no new cases ol silicosis developed in this group, in spite of the fact that the men 1948, only about 8% had deteriorated. Of the 15 commercing aluminum therapy with a measurable degree of functional incapaci tation, about 7% showed no progression of their condition, about 135b became aggra Tabs.* 4.--Changes in ike Functional Lung Capac ity of Ail Foundry Workmen (239 Work men) Subjected to Period of Aluminum Therapy 2943.tt$4 vated, while the balance (80%) improved, with 735k reverting to normality (Table 2). The remaining cases in the miscellaneous group showed much the same range of re sponse to aluminum therapy, Three out of one hundred six normal cases deteriorated uo,.. mt... 1*3... T*7 UtH,,, >>i>f fvoo UOB SUUtf too. Its. ( Oopijwraa IX 8 l Onistpmod 1 iBapn>vd * J u m despite therapy, but the balance showed no 0< t ill vbe ttopp*. n wen aero*} as Uw daw progression. This result may seem excellent, ef final uaeMtMBt Is 1M. but it must be recalled that this is the group of foundry employees for whom a six-year period is less critical in respect of the rate at which they develop silicosis or advance to disability. Of those 82 employees in the miscellane ous group who started oS? their period of reported on had work exposures of signif icance prior to 1948 when aluminum ther apy was started. A. similar observation was never recorded in any prealuihinum year rn this foundry. SUW*.RV t. Two hundred eighty-nine foundry em Tabu X--Change in the Functional Lung Capac ity pf Foundry Mistel'emetn* Croup (J& Workmen) Subjected to Period of Aluminum Therapy--l94$-19S4 ^SES+m*"S5ffZZZSSE^^ESSSm2SSSSS22S^SSS~m+?^SSEES2ii*E321^S^^^^SES} T*r 14*A.. LUA* tfcaSu&M XOJTBAI r Oaftium* f wm St&aonsft) l Atraraed ' \ IZDproved ' Mfo,tro. m M6 5 '68 n * Ot tpn *6 w&o Intwwef, < At BCti ftMMTMnt (6 rftM. umil titM ployees were subjected to aluminum therapy for a six-year period, 2. The average exposure to aluminum was 230 minutes per person per year. 3. It is estimated that each employee re ceived approximately 1650 mg. of pulverized aluminum per annum. 4. Of the 164 men commencing aluminum exposures with normal functional status, 95% were unchanged and 5% had deterio rated at the end of six years. 222 CONTROL OF SILICOSIS *?--,*;* . 5. Of the 125 men starting with a measur able degree ,of functional incapacitation be fore aJiamuajo treatment was instituted, 9% deieriomed further, while 90% improved, and of the latter group 77% reached nor mality at the end of this period. 6. The incidence of new cases of radiolog ical silkosis dropped to zero Airing the years 1953 and 1954, which is the first time this has happened in the history of Oils foundry. INFERENCES 1, Hasson, J. W. G.i .felmmoum Thera?/ In the United States, Tr. Canad Ion. Uin. it Metal. <7:I80-1$4, 1944. 2. Cole, L. C, and Cole, W. G,: PaeoBwamtosis (SiliOKis): The Story of Dusty Langs, Kew YoA. John B. Pierce Foandation, 1946. I f l 1 I I 22J 4 i f-^roplyictxid and J*Jrealment oj ExperimentalSilicodid by ^lYjeans ~dlli umuium A* Uudj M. BW0KSKI, M>.HV fe'eMC Uk*, K Y. animal, the desire to discover the cause of the toxicity of quartz and to find a means to prevent the disease became a major objective of the research program of The Saranac Laboratory. There was, however, as even Tlie studies presented herewith, which were a major interest of the late Leroy LL Gardner, M.D-, and occupied much of his time during the last eight years of his life, comprise a total of 43 systematic experiments, some of which terminated her his death. la May, 3944, Dr. Gardner delivered the Donald E. Cummings Memorial Lecture,* bigger stake involved than the development of a method to prevent silicosis, for It was hoped that. In determining the cause of the toxicity of quartz, an answer might he ioood to explain the increased susceptibility to tuberculosis in the silicotic host. Before describing the experiments, it may be of historical interest to explain bow H entitled `'Aluminum Therapy in SBkosis,'' at happened that The Saranac Laboratory dis the Annual Meeting of the American Indus covered that colloidal aluminum hydroxide trial Hygiene Association. He presented exerts a protective, effect against the toxic some of the essential findings of the studies reaction of silica in tissue. When, in 1932. which had already been completed and de scribed the experiments which were still in progress. He concluded from experimental evidence then available that "aluminum Kettle* reported that particles of quartz coated with iron would not produce a silicotic reaction following injection into animals, an attempt was made at The Saranac Labora agents in propes form constitute an effective inhibitor of quartz in a living host." With the establishment of the fact that silicosis can be produced in. the experimental Recorded for pubtkatiea June 6,195$. Research Associate, The Saranac Laboratory. For she design and c<*wh*i of the experiments oo which this paper is based, all credit goes to the Wit Leto> U. Gardner, >SJD. Recounttkt should W given aUo to A. J, Vor*alA M.D, A, Q. Delatest, S. L. Gockeler, A. J, Redlin, and F. T. Creedon for assistance in many technics! phases of the work and w't.H.Puritan, U.H., and G, W. H. Sdseper, itf,I>, D Sc, for assistance in the preparation of the paper- tory to repeat his experiment. Kettle did not describe ins method. In a personal coromucu ration to Dr, Gardner, he stated`that the chemist *lw> prepared his coated quartz was no longer accessible, but he suggested that the quartz particles be boiled In a solution of colloidal ferric hydroxide. Dr. Gardner found, however, that quartz particles treated in that manner still produced fibrosis on in jection into guinra pigs and rabbits, although the tissue reaction was somewhat delayed. For a number of years thereafter, experi ments were conducted at the Laboratory em ploying various agents in the hope of pre* 224 < TREATMENT OF SILICOSIS BY MEANS OF ALUMINUM veonngthe silicotic reaction, either by neu tralizing the charge or by coating the silica particles. Among the substances tested were acacia, sodium cleate, various forms of char coal, precipitated ferric hydroxide, night blue dye, aluminum phosphate, and colloidal aluminum hydroxide. Of these, colloidal aluminum hydroxide was discovered to pre vent the toxic effect of quartz. It was found that when quartz particles, 1>> to in diam eter, were suspended in colloidal aluminum hydroxide and injected intracardially into guinea pigs the silicotic reaction in the liver and spleen, where quartz particles of this size are retained, was completely inhibited. Publi cation of the findings at that time was con sidered, but, because of the uncertainty of the permanence of the protective effect, it was decided to follow the observations for a year f.jno?c> Other experiments were started at iaj^fer to verify and supplement these dal^dings and:to define 4he conditions jmdetf^&rcol&d^ aluminum hydroxide ^ould^e mOst effective. ^ItwaSwitKgreat interest that the.staff of Laboratory read, in 1937, the tejx>xls.'<rfT>nny, Robson, And Irwin* in ?hi&tfiey stated that they were able to pre ened* Silicotic reaction In rabbits by means ' 'u ** HdpJehdfic aluminum. In Novem- 7, Dr; Irwin visited The Saranac itory aid described their work. In Gardner demonstrated to him that qhkrtz particles suspended in colloidal alumi num hydroxide and injected into guinea pigs produced a reaction limited to simple phag ocytosis. . Dr, Irwin sent to The Saranac Laboratory some of the metallic aluminum powder he used so that the relative effective ness of the metal and of the colloidal hydrox ide in protective experiments could be com pared, TECHNICAL PROCEDURES 1. Dswamrio* ah* Meuic or P*zfa*atiok Of VAJUOVS F<XMS W Ai-UKTKVM EmWAIVE IN TBS EXTUiWZKTAl- WCK IK THE Sarahac Lasosatohy The aluminum compounds used are sum marized in Tabic 1 and deserve the following further comment. (a) Colloidal Aluminum Hydroside.-- This is the colloid that was first used in our experimental investigations. Except for a brief description contained in (ho paper by Gardner and associates,1 no detailed account of its preparation has been published. Orig inally the colloidal hydroxide was prepared as follows. A 3% solution of aluminum chloride (AlOf-dHaO) was heated to boiling, and concentrated ammonium hydroxide (NHOH) was slowly added, with continents stir ring, until a very faint odor of ammonia Table l^Aluminum Compands V**d (l) OeBoMtl itemfaos) bydrortdc, This wBpoo&d 'sbnyypvnaddsiisutTfebs* 6roa2Ue LL*0tr8tS. J*ory iron AtO* B*0 <I) fflfjBij ftmtnwa byflrou. TS!i eeiopQtwS. mm* u *m m&rikJn prepr*i by tbe Aft. ntssn OMSMsy < AaKrte* Iron odiora tltuatBat*; Um I'Rt efflnO0B pattern ot Hw ft *fstSr to tte'Smbni obtained Iron tbe eoQoWal kituateam hjOroxMc propon* ft Tft# Samtoe Laboratory; H-iMfl < sand te tnhflaticg apadBieUL on jfebaft' slyuiiindw pevder. TJw nwtalBe tfe&iftBjB sorter art ft lb UMlas apulocsu u furtrtrt by >r. 0- A- trots,ionwrij el tbe Statical KaaeaKb Desattmant of m uiSirtltT oi Toros to; tbe nseUIBs EasSoB porte* lor b* inbeUMoo caperftaaft v tmyarodtro paSsu ol alwolowD yroead ft * *-rot*dug drua aoe mu blows ftte tbe eoKfet* room by ce&prested al. persisted, This produced a voluminous gelat inous precipitate represented by the follow ing reaction.: AJOrf3NK^H==AJ (OHM-3NH.O The suspension was filtered through paper, and the precipitate washed with hot water to remove most of the soluble ammonium chloride. A faint trace of the chloride was allowed to persist, because otherwise, as we discovered, no stable colloid would form. The moist precipitate was removed from the filter paper, resuspended in distilled water, and placed in i 500 ml. or larger graduate. After settling overnight at roam temperature, the supernatant fluid, which was a viscous milky colloid, w4s decanted off and reserved, and the gelatinous precipitated aluminum hy droxide rajthe sediment was discarded. Later, the method was modified by substituting cen trifugation for filtration. The hot, freshly precipitated aluminum hydroxide was cen trifuged for 10-minute intervals at 2000 rpm. isAs long the supernatant fluid remained 1 22$ pworski dear, it was discarded, and the sediment was was allowed to dry on the filter paper. It was resuspended in hot distilled water and reom- thee removed from the paper, placed in an mfuged. Four or five centrifugations were evaporating dish, and dehydrated over sul necessary to remove sufficient ammonium furic acid *n tticuc. When thoroughly dry, chloride in order to convert 3 portion of the gelatinous precipitate to a stable colloid. At this point the supernatant fluid assumed a milky viscous appearance similar to the col* loid obtained by the overnight sedimentation obtained in (he first method of preparation. The milky supernatants were collected in a flask. The pH of the collected supernatants tended to range from 5.8 to 6.4, indicating that the colloids! aluminum hydroxide pre the sffiafl dumps were ground to a fine pow der in an agate mortar. It was resuspended in distilled water as needed for use. Such a suspension does not become as viscid as tKc original colloidal aluminum hydroxide. It is also nondialytable and has the same pH as the colloid. When suspensions of this powder and quartz were tested in animals, st was found that the drying did not destroy the inhibitory action. pared in this manner was acidic and that its formula may be expressed as HgAIO* to emphasize its acidic nature. It remained stable as tong as its reaction remained acid but did not pass through 3 cellophane or collodion membrane. X*ray diffraction ex amination of the colloidal atommum hydrox ide after evaporation to dryness in the open air revealed a weak pattern of aluminum -trihydrate. When the colloid, after evap oration, was dried in a vacuum, an. extremely fine-grained aluminum -monohydrale was formed. The absence of any dUtiuci tinea in the pattern of the vacuum-dried material indicated that the product was chiefly amor phous in character. Chemical analysis of tlte dried colloid showed that it contained 3.40% chlorine. The water toss after ignition was 25.3!%. The colloidal content of the fluid was de termined by converting aliquots into alu minum oxide (AljOj) and calculating the aluminum hydroxide content by the factor i .53. This was done by evaporating 10 ml. quantities of the colloidal aluminum Hydrox ide on t water bath in a weighed crucible, The crucible was then heated over at! ojjen flame to a constant weight, thus con After it was demonstrated that a pow dered form of aluminum hydroxide was an effective inhibitor of silicosis, the labora tory was confronted with the problem of producing the powdered aluminum hydrox ide in sufficient quantity for long-term in halation experiments. Dr. Francis C. Frary, Director of the Research laboratories of the Aluminum Company of America, was con sulted, and he expressed his willingness to cooperate. After submitting several different forms of powdered aluminum hydroxide (C-730, C-732, C-730 activated), which were tested and found unsatisfactory, the Aluminum Company of America prepared a powdered aluminum hydrate designated as H-5050. This product, when tested by infec tion methods, proved as effective an inhibitor as our colloid and powdered aluminum hy droxide. It is this product---H-101O--which has been studied exhaustively in a series ol inhalation tests involving normal, silicotic, and tuberculous animaH. The x-ray diffrac tion pattern of H-1010 is similar to the pat tern of the vacuum-dried compound made in The Saranac Laboratory, The product H-1010 is principally aluminum hydrate, which is possibly to a Urge extent amor verting tlw colloidal aluminum hydroxide phous and contains at least some of the {Al[OH]) to aluminum oxide fA10*). tt-monohydrate. The effects of these differerM (b) Ppwdergd Aluminum Hydraie.---Pow forms of aluminum compounds suggest dered colloidal aluminum hydroxide was pre that their amorphous component may be tlje pared from the colloidal aluminum hydroxide active substance that inhibits the quartz and described under (4). The precipitate, after prevents the development of fibrous tissue being washed free d most of the chlorides. reaction. 226 TREATMENT OF SILICOSIS BY MEANS OF ALUMINUM r(e) Metalik Aluminum Pewdn.-- The experimental support from studies made in jtataJlifi aluminum powder employed is all The Saranac Laboratory. Repeated tests injection experiments was furnished by Dr. made on carefully sited particles, Ifi to 3/* in V: A. Irwin, then of the Medical Research diameter, have shown that many physio Department of the University of Toronto. logically inert silicates yield more "soluble It was acetone-washed and finely divided, silica" than does the very pure quartz which hfore than 90% of the particles were less produces the siKcotic reaction in tissue. From dan l/i in size. The metallic aluminum pow work done by Gardner and Redlin4 and by der for the inhalation experiments was Filley and his associates,* tiw* hypothesis has freshly prepared from pellets of aluminum been suggested that the toxic effect of finely ground in a rotating aluminum-lined drum divided quartz is confined to the surface of and was blown into the dusting room by the particles where a layer of highly toxk compressed air. The powder prepared in this colloidal silica is liberated. Scheel and his as manner was finely divided, and more than sociates * have demonstrated that a film of 9&Jo. of the particles were less than 2/* in protein is adsorbed from solution by quartz dmeter. Occasional dumps, varying from particles 1/* to 3^ in diameter, and Schepersr 20/* to SO/*, were present. has shown that the presence of this protein The x-ray diffraction pattern of the metal film radically modifies the cellular reaction to lic aluminum powder was the same as that quartz. Regardless of whether the toxicity is . of the standard pattern of crystalline metallic due to liberated colloidal or soluble silica or aluminum. When the metallic aluminum to the adsorption of protein on the surface of powder was suspended in distilled water and the quartz particles, the protective effect of allowedto remain in an incubator overnight the active aluminum compounds may be in It 37 C, the hydrate was formed, which terpreted on the basis of the inference that Tclded an x-ray pattern similar to tlist'of quartz particles are rendered inert by an in he other aluminum compounds, Denny, Rob- soluble and impermeable coating. on.'.and Irwm4 assert that the metallic dudaobrn hydrolyzes when it comes in con- jsctlvrth the body fluids. Examination of the diffraction patterns of the vacuum- dried->nojda! aluminum hydroxide, the Hr10I(>powder, and the hydrolyzed metallic alurrtfmlm powder revealed that the materials to large,extent amorphous bqt con ned sa^albamounts of q-raonohydrate and *trihy3tate of aluminum., . c '* Thbihrec.aluminum compounds--colloidal hydroxide; 11-1010 powder, and metallic powder--have the faculty of depressing mark edly the solubility of quartz as determined by the molybdate method; in fact, the aluminum compound reduced the amount of silica in solution to l^of the value before the alumi 2. Vvzpamatiq* Quastz Factions tot JxjeCTTOM ABO IXRALATiOX All die quartz used to the various experi ments to be discussed was prepared from a finely ground commercial product. The SiO* content of the material was 997%, and x-ray diffraction examination disclosed nothing but normal quartz. For injection tests, the com mercial product was reground in a steel ball mill aridelutriated to water. Particles meas uring between l*and 3* were separated and used in the injection experiments. The par ticles were routinely suspended in 0AS% saline solution or to colloidal aluminum hy droxide and sterilized in an Arnold sterilizer for one hour. num was added. This observation formed the In the first group of experiments, injection basis for the theory that the toxicity of silica techniques were employed to produce the is due to the release of minute amounts of silicotic reaction for th* quantitative assess soluble silica in tissue. The assumption, how ment of the inhibitor effeas ! the aluminum ever, that the soluble silica demonstrated compounds, later, wfsro the powdered alumi colorimetrically in vitro is responsible for the num hydrate H-103' and the mill for produc silicotk reaction in tissue has not received ing metallic ahmurntr der became avaiki- DWORSKT bfe, inhalation methods were employed, both as a procedure for causing silicosis and as a means of introducing the aluminum com pounds into the experimental aoithal. The intravenous injection of quartz particles into guinea pigs and rabbits produces marked sili cotic reaction in the liver and spleen. The pre vention exerted by the aluminum compound against the fibrotic reaction, particularly m the liver, demonstrated the principle that the inhibitor and the silica particle must localize >n the same phagocytic cell. Injection Method**--The quartz employed in the injection experiments was the specially pre pared pceder composed of particles I* to 3* in diameter. It was suspended lo Isot-orrk saline solu tion or in a suspension of the aluminum st&rtaoee to form the desired coccentration. The injection techniques beloded the intraperitoceai, the istrmvascolar, and the intratracheal methods. In the rntraperitooeal method, a single dose of 2 ml. of a 30% suspension o( quartz particles <200 n*g<) was injected into the abdominal cavity of a gukea pig. When the intravascular technique was used for guinea pigs, ] ml. of a 1% suspension of the quartz pa'tkies was injected directly into the left ventricle of the heart twice a week for eight weeks, until 156 mg. of the dust had been gives. For rabbits, 5 at of a 1% fespenrioe of the dart was injected into the ear vers twice a wetic for 30 wedcs. The intratracheal technique made ose of a tracheal cath eter through which the dust suspension was intro duced into the trachea of guinea pigs, sate, or rab bits and nxbseqoezrdy passed into the hvtg. The dose was 6.5 ml. of a 10% suspension, and it was given once a week for three weeks. inhalation Methods.--The methods far exposing animal* to sillea dust inhalation have been described In detail in other pul>Jications.*1 Briefly, the tedmique consisted of the exposure of animals to a cloud of fine silica particles disseminated m the air of a room by means of mechanical devices designed to produce Che desired duperyfoa and ceocentnitiart <d particles in the atmosphere Samples of die atmospheric dust were collected from time to time by means of a Gieenburg-Smtth impinger apparatus. In the ex periments reported, a concentration of shea parti cles ranging from 500,000,000 to 700,030,000 parti cles per cubic foot of air was maintained. Ao analy sis of the slat distribution of the particles showed that more than 99% were less than 10** in diameter. Chemical analysis showed a total silica content greater than 99%, Atmospheric- concentrations ranging from 1 to 3 mg. tier cubic foot of air were maintained in the rooms in which either aluminum Table 2.~~St*xiUj ef the Prophylaxis &h4 Treatmen* ej Erfierimeniol SiHeotU by Meant oj Altmtnvm ______ (t> Effect of afeBfaoB eetspeeai)* oo arm> salsuls tt) oPvraevnbsfiaetta eetloa or Jumtoom eeBpoa&4e n (8) Tbersveutie effeet ot sKaosteun eaapw*** so an, esuMssM ameotk Moms (tl SOsccetstoOtlavta ewwfle& va (Oeeo<tt*e i artermtooj latauoo la enaaate not pom to qsartr dust. hydrate H-1010 or metallic aluminum powder was dispersed EXPERIMENTAL FINDINGS Use experimental findings will be pre sented in the order shown in Table 2, 1. Evnscr or Aluminum Compounds on Normal Animals (a) Colloidal Aluminum Hydroxide.--iThe results of & series of experiments showed that normal guinea pigs and rabbits receiving re peated injections of large amounts of col loidal aluminum hydroxide remained ap parently healthy. The reaction to imraperitoneal injections of the colloidal hydroxide consisted of the formation of Sat white plaques oa the omen tum and peritoneal surfaces. Throughout a period of one year of observation, the only change observed in these plaques was the formation of a capsule composed of a thin layer of connective tissue, while there was no reaction in the adjacent tissues. The occur rence of increased numbers of phagocytes in the lungs, liver, and tracheobronchial lymph nodes suggested that small amounts of the aluminum agent had been transported to these organs. One of Gardner's experiments led to the observation that aluminum-containing phago cytes altered the lung from the peritoneal site. This experiment was executed before a powdered aluminum hydrate suitable for in halation had been prepared. The attempt to introduce the colloid into the longs from an atomized spray proved ineffective, A group of 20 guinea pigs was, therefore, exposed by inhalation to a concentration of 800,000,000 particles of pure quartz per cubic foot of air through the course of one year. Ont-haK of the animals received in addition biweekly 228 TREATMENT OF SIUCOSIS BY MEANS OF ALUMINUM jntraperitooeal injections of 2 ml of a 02% similar cells were present A similar localize suspension of colloidal aluminum hydroxide, tion of die colloid occurred following intra and the other half served as the quarts con venous injections in a rabbit. trol. Two animals of each group were killed at intervals during the year. Is the groups of animals Id[fed at the end of 10 months, gross and microscopic examination showed that the silicotic reaction was definitely inhibited by the hydroxide which readied die lungs from the peritoneal cavity. It* tings c/ the control animals showed widespread fibrosis with nodulation, gome with necrotic centers and beginning hyaKnization. The silicotic reaction m the treated animals was limited to prolif eration of macrophages and infiltration of lymphocytes {Fig. 1). Hie definite inhibition of inhalation silicosis by intraperitooea) its- From these observations it was concluded that normal guinea pigs and rabbits are not seriously affected by repeated injections of Urge amounts of colloidal aluminum hy droxide. The phagocytes apparently retain much of it for at least one year. (fe) Powdered Aluminum Hydrate H1010.--The results of experiments by injec tion and inhalation showed no evidence of any toxidty or any chronic change which appeared to affect the health of the animals. The aluminum was apparently also retained for at least a year. An inhalation experiment in which healthy 5*3* guinea pigs were exposed eight hours daily .Tor one year to an average concentration of t i;F.5 tng. ' of powdered aluminum hydrate r WPrctctXW'K?*gBiast inhalation silicon* by tob'ofta) siuounom hydride sstro^Ked Mfcritant*3 injection. Experiment 790-- ,?gsddt)S'fw 10 months. Wbok langfec* ...__A, hmg of animal exposed to quarts inhatetlon, with shnultabeous trestmoit by means of bi weekly paraperitoneal injection of 2 ml. of 02% suspension of colloidal alumamm hydroxide. B, fang of <?uam control without slummum treatment; nodtdadon and necrosis and incipient hyaluiiratjoo contrast with complete absence of sitkosU is the aluminum-treated animat. jection f the colloidal hydroxide intensified the efforts to prepate a powdered aluminum hydroxide which could he suspended in ait and inhaled as dust. It was found that after intracardial injec tion of colloidal aluminum hydroxide the greatest accumulation of the colloid occurred in ctUs of the reticuloendothelial system of the spleen and liver. Isolated pant cells, clumps of mononuclear cells, grayish blue in color, were seen in the pulp and follicles of the spleen. In the portal area of the liver. H-1010,per cubic foot of air demonstrated that there was progressive accumulation of the aluminum compound m the lung. Gross inspection of the lung at the end of the year showed a slight diffuse tan pigmentation an teriorly. Microscopic examination revealed localized peribronchiolar fod of alveolar phagocytes sometimes surrounded by slight infiltrations of lymphocytes in adjacent walls. The phagocytes were markedly bluish gray and often swollen, and aluminum particles could be seen in their cytoplasm. The tracheo bronchial lymph nodes showed heavy diffuse mononuclear infiltration with no evidence of fibrosis. (e) MelaUk Aluminum Powder.--Diffi culty was encountered in preparing suspen sions of metallic alumioum powder for intra venous injection into animals. In an inhala tion experiment with powdered metallic alu minum, in which guinea pigs were exposed for one-half hour daily to an atmosphere con taining an average of 0.8S mg. of metallic aluminum perj cubic foot of air, no gross change was noted in the lungs until the ex piration of one year, when a few small dis crete foci of black dust appeared. The size of the fod had increased by the end of two years to 2 mm. diameter, but the number of foci did 229 OWORSKl cot materially -increase, Chemical analysis of the lung for aluminum showed no additional accumulation of the.metal aftqr the first year exposure. The tmheobumth^ lymjfc nodes were slightly firmer, with little pig mentation at the end of one year and with increased pigmentation at the end of two years. There were no gross changes in the spleen, liver, kidney, and hepatic lymph nodes. Denny, Robson, and Irwin* exposed rabbits 12 hours daily for 14 months to an atmosphere containing freshly ground par ticulate metallic aluminum powder. Although the lungs contained 270 to 1200 mg. of alumi num per 100 gnt, of dried tissue, the authors reported no evidence of toxicity or damage to the tissues. 2. Pmphvlacrc Actios or Aluminum CO*WKBS-A<UiKSr -QUAKZ The prophylactic effects of aluminum com pounds have bees studied in differeotexperiments involving guinea pigs* rats, and rabbits. The aluminum agents were administered by injection' of by hihafatioti, either prior tcUhe exposure of the animals to quartz dust or su&nlUrmKty with the exposure to the quartz dust as a mixture or as separate com ponents. . A group of experiments employing the in jection of colloidal aluminum hydroxide demonstrated most conclusively the inhibitor effect o! the hydroxide'Though the reaction took place in the liver and spleen, the results are considered valid, because it has been shown that free silica has the same effect upon connective tissue regardless of the organ in which it is located. The connective tissue of Taauc 3.--Df$rrts of 7'ujw Reaction Produced by Quart* as a Measure of ike froiecftvt Effect of Aluminum Confounds Ex>rt. QAHtfti SSeoak 1,8.4 S-fi.I s. s-s E. 9.4 , 6,4 *rwumifc 7m run ol UmJUmUoa bnmot Pretacetoa br AfofB&OB) Gtmph pbaeocrtABk; tbit k W< ma) alUcotte iJoq, JodJeiU** e*>oBn&pOteUtSeXpl rotocUon by lustouin A. P,4 831*00? temurt BOtabert f p**. txfU* oauatty appeartaf To retail eoiBptce ebstapt, Jodkt*uc tttat i*ntoto sn fca Wfuttei !tlwat a*fHo* m? aporedtbfe eflarti udob rerroaM. 1st tkSOeO There is M aa 4duWQ8) InftJ- trttieo el JTtaofrotfua sa to* tonMdJaUi eiciflJt* of t&e rianpt el pbaAocitto; tbl* uveites erl* Oe*m ol ehroafc baonabUeo A. P.4 A. P.4 ProBferetfoB of jibarocrfe* tad a, P.4 {nsdmUrsltefoaek*etelaJorau&t tMawcysaiaa;wtaMfet od* peruui? prcteeUv* WkWpraoC 6bro*i vtth Mrofi: A.P.-1 ftUleotie *c4eoQ k aMebilr tefonfirf Uetart brtlbe affieotk ooctaka; tAk toloa njinTin u&4rd Wmtoal reteOoB te mart* pr> tkkt, kakattat bo prourtive MTw from BJosttrest A. p.4 the liver which reacts to the silica is com posed of the same cytologicaJ elements as the connective tissue of the lungs, although the tissue assumes different forms in the two organs. The capacity ol the different aluminum compounds to inhibit the silicotic reaction has been determined by the cellular response of the tissue to quarts particles, and the results are presented in a series of tables. The scale or Severity of the silicotic reaction and the degree of protection afforded by aluminum are summarized in Table 3. Table 4 lists the results of a aeries of ex*, periments with colloidal aluminum hydrox ide. The control guinea pigs receiving quant particles suspended in isotonk saline de* i able 4Protective Effect of Aluminum Hydroxide Agemtl Quarts Injection Experiments--*Quart* and Aluminum Hydroxide Uixed Exp_ No. 7*fr* *7 ST6 028 m gpCfctOf AB(CB8) GbUci pi* GaUMpt* OcbBB We ExtPit AaJnab. Wo. s s ft * IstttUos took U (nperttoBsaJ KtracdAHoj jptfacahUal Jslraeardfal ttftraiVttotta AlaurtflotB 4**M EapfoyM AJiOH;, AlaOS). AKOID* homo A)<on) * Ouam wrOci** used ** j* w> * to dieou;. 230 or Afoot. QUID, K*. 4 40 X $s VQ Ul of QirtfU,* M*. too 930 160 m 600 Ol Obaer*W. Me. is it it 12 2! SHWoite RarUOfi .8.4 Bfi-4 E84 8.4 E4 Prottruos bt AlusLi&tun A.P^S iJ-4 A.P^ft 1P.4 TREATMENT OP SiUCOSIS BY MEANS OP ALUMINUM yeJoped characteristic silicotic lesions in the spleen, liver, lymph nodes, and bone marrow, ,, During the first four months there was rapid proliferation of mononuclear cells in focal areas associated with degeneration of thecon tiguous parenchymal dements. Eight months after completing the injections, most of the silicotic reaction in all these viscera had at tained maturity and was composed of more or less hyaline fibrous tissue. The guinea pigs receiving the same amount of quartz particles suspended in colloidal aluminum hydroxide showed no nodule formation or fibrosis. The primary phago cytes ingesting both the quartz particles and the hydroxide did not proliferate but re mained widely scattered throughout the tissue. There was no evidence of injury to the cells. The histological picture remained unchanged \2 months after coropkdag the injection, as it had been in the animals killed at one month (Fig. 2). In order to be certain that the associated aluminum substances had not altered the distribution of the injected quartz particles so that they no longer ac cumulated is the usual viscera, the livers of all animals in this experiment were analyzed chemically. The analysis demonstrated that in all groups there were sufficient quantities of silica to have produced reaction (Table 5). Fig. 2>--Complete protection afforded by colloidal aluminum hydroxide against hepatic scle rosis trow Quartz diet. Experiment 747--guinea pigs; result at end of one year. Microscopic sec tions. A, liver cl treated animal, showing no cellular rmdtiplkatiOQ or colloid B, hver of untreated control, showing hyaJtrttring nodules. . Table S.--S*l*ro Content of Desiccated Livers of . Cuinee Pigs That Had Received by Injection V, Quarts Particles Alone end Quarts Particles in an Aluminum Suspension* ............ ....... ....... ........................................... I II.. _ at ExpOttR, Ho. 1 8 Ur QutrU Ftnkfes at*pefidd Jiotonle a*Bw Oocirob, % iAt IM 9M Qtiim pinMtt Butpeofled aicoh>. % in 083 083 Outni Ftflkh* Buepesded lcm% MelaSie A! Fo4*r. % lD i.to i.a 1ST * A tat*! 4om ot SX me. at writ ptrU&es. lg tt>*g tlaaeur, * to'rodunri ftto tA <trro!*llon ul Mtb In all experiments employing the injection of colloidal aluminum hydroxide and pow dered aluminum hydrate H-I010, the silicotic reaction was inhibited. On the other hand, animals treated with powdered metallic alu minum showed only a slight inhibitory effect of the aluminum agent on the silicotic reac tion. Seven different injection experiments were performed, and the results were in variably poor. When the metallic aluminum was suspended in OSSfo saline solution or in distilled* water, the suspensions flocculated, and no dispersing agent that we tried could 231 DW0RSK1 prevent the formation of large clumps of the powder at the point of contact with body fluids. On injecting the suspension ofMetallic ' aluminum powder and quart* particles into TaaSX 6*--Amount of Aluminum Retained ts Liver and in Spleen of Guinea Pigs After 2*traeerdial Injection of Suepeneio* of Colloidal Alumi num Hydroxide and of Powdered Metallic Aluminum - < the guinea pig heart, most of the metallic aluminum powder rtmaitved in the eatdsat ventricles, while the quartz particles were carried to the spleen, liver, and lymph nodes where they produced silicotic fibrosis. There was correspondence and consultation between Dr. Irwin and Dr. Gardner regard ing the difficulties with the metallic alumi num. Dr. Irwin held the view that, if the roetallic powder depressed the solubility' of ?Um ,----------I-iaw.--------- *tur ColbiO*! UeteBk lojwtioc. AJ(0H>., S3, Mo. Me. 1 ST t HA t *?. a $ OJD 12 U.l 0X6 HonaI eostroii 664 ,---------S--M----u--- ------ , CAo?<tMOdH%>.]. Meullk A), it 14S4 tUJ J.J Ut.T 44 OX 0(o846 *Tfc# two tUMpuuloae coatuaad qu(*Afefit taoosO of Juatfjwm; tCus )ven ate tnl&traa* of AS eoapoosot per no tea. of Artec tissue, quartz in the test tube, it should possess the property of inhibiting the toxicity of silica. Tests showed that the.solubility of the quartz was reduced 9Sfo by the aluminum powder. Dr. Irwin suggested that the tissues be ex amined for soluble alumsxfem by the aurinstaining method, but the sections of tissue so stained showed no aluminum. Chemical anal ysis of the tissues for aluminum disclosed that very tilde metallic aluminum was present in the tissues, in comparison with the amount of aluminum found in the hydroxide-treated confirmed these findings. Apparently our in ability to prevent the flocculation of the metallic aluminum was responsible for the absence of the protective effect of the metal. Further injection experiments with metallic aluminum powder should be planned, utilis ing the newer dispersing agents now availa ble. If the metallic aluminum can be localized in the liver and spleen, a protective effect against quartz particles in these tissues simi lar to that observed with colloidal aluminum hydroxide should occur. animals. In an intracardiat injection experi ment employing both the metal and the hy droxide, in which equivalent quantities of aluminum were given, 25 times more alumi num was found in the tissues of the guinea pigs receiving the colloidal aluminum hy droxide than in the animals into whkb the Experiments in which groups of rats were exposed by inhalation to an atmospheric suspension of H-J010 for varying periods of time prior to exposure by inlialatioa to quartz particles are listed in Table 7. At the end of a year there was evidence of seme inhibition of the reaction to the silica, but in none of the metallic aluminum suspension had been in animals was the protection complete. The jected (Table 6). Two other experiments degree of pfotectfon was In proportion to the Taxis 7.--PraUctiut Effect of Aluminum. Compovnds Ag&nsi Quarts* Exp., No, SSi'i oft-ir bwjv W vm Specie* oj AUB*t Bat Aslcials. Bo. ss Bat Si Btt n Bat a Bat 40 Qufoia V* u AJOBCetUS Anst raptor4 H-1M0 H-iCO H'10!O H'jose B-tQio ninttoB of Erpoftrwto .Humana* 0 br, Atfly for so. S hr, 4tUi for S ao. S br. duty rot 1 00. e far. d*rir for 8 wk. Hforbnr. AaaQoy. Vfhi.tntoj for ao. Ouratloe of fZzpoaunte Quarta S br. dUiy fori yr. 8 be. <UUs for l yr. s br. OaUr (or i yt. 8 br. au)r tor i ft. br. 4taj for 1 yr. Tfcir. mr tor ts ao. SBratte Tra fteartfoa B&.4 RA.4 E4.4 R4.-6 4.-4 13-i Protection h* AXtabos A.P.-5 A.T.^ A.P.t A.P.X A.PA A.P.0 lubahtfoa o( H-lOlO powder A<t of aetalttc ahuaJavia pouter foltowert 67 teAtUtlOB of qu*iU duit. Co(RBtratM oi K-IC36 powder; to 60 me. per ruble foot of Air. Coates tmtoxi of queru east: THO.eo3,a particles per euWc foot of Air. 232 TREATMENT OF SiUCOS/S BY MEANS OF ALUMINUM .-v-.Nj; . < y ry `` * l-yftt.JEf Fig. 3,--Prophylaxis against experimental silicosis. Experiment 984-1--admmistraDon of H-1010 agent to rats preceding exposure to quarts dust. Microscopic sections. A, lung of aJunimsQ-treated animal; reaction limited to focal ceOuIar reaction without cottagers forma tion. Bt lung of quarto control; fully formed blinking nodules have developed mrV* Fig. 4.--Partially effective prophylaxis against experimental siIkosU by means of R-1010 aluminum agent. Experiment 98S--rats. Microscopic sections. A, long of aluminum-treated unlmat at end of one year of exposure to qssrtt dost lot seven and one-half hours daily, pre ceded by one-half-hour exposure to H-1010 aluminum agent; small cellular nodules only have developed. B, lung of quartz control without aluminum treatment; at fjid of eight months there is 4iBu*e fibrosis. duration of prophylactic treatment with B- v&fc - - 1010 and to the amount of H-1010 found in the lungs by chemical analysis. In those ani mals which inhaled the aluminum agent for --'Isnfcjv*-* hours a day, the Itmg showed 42.3 mg, flifefefcy.j-rf aluminum per 100 gm, of dried lung at *i ' 1 *k. the end of four months, compared with 7,5 mg, of aluminum at the end of two weeks. In the`groups of animals treated for one, two, and four months, respectively, by means of the inhalation of H-1010 before exposure by inhalation to quartz particles, evidence of 233 *TM> OfTOKSKI inhibition of the silicotic reaction was demon tection than was found in the rats exposed strated. The Jungs of art animal killed one to U-1010 on the same daily routine. At the year after exposure to the Quartz particles end of one year, microscopic examination of showed a histological pietur^of widespread the lung showed extensive dust reaction, with focal cellular proliferation, with no necrosis marked proliferation of macrophages in all .or hyalmiration. The lungs of the untreated sites of localization (Fig. 5). A distinct animal showed large hyaline nodules (Fig. nodular pattern vrith small central hyaline 3). fibrosis was observed in many lungs. Obser An experiment in which 40 rats were ex vations were continued ior 20 months, but posed by inhalation to H-J010 for half an intercurrent infections interfered with the hour daily, and then were transferred to an study in the latter part of this experiment. other room and exposed to quartz dust for Chemical analysis, however, showed that seven and one-hslf hours daily, demonstrated some metallic aluminum had accumulated in some inhibitory capacity of the aluminum the lung. agent, but the protection was not complete. The rats were observed for a period of one year, and the nodules did not become large enough to be recognised on gross inspection of sections. On microscopic examination, rare nodules were seen to have necrotic centers in some animals. There was incomplete pro tection in the lymph nodes. In the control ani mals, however, fibrous nodules were macro- seoptcaUy visible alter 8 months, and the animals died before the 12th month. In die treated group, six animals were killed at the end of 32 months in order to terminate the experiment, but none died spontaneously (Fig. 4). An experiment In which 25 guinea pigs were exposed to 08 mg. of powdered metallic aluminum per cubic foot of air for half an hour da&y, followed by exposure to a high concentration of quartz dust for seven and one-hall hours daily, showed less pro Fig, 5.--Incomplete protection agabst tibcosji by tfwani of powdered metallic aluminum. Experiment IMS--guinea pigs exposed daily for half an hour to powdered metallic aluminum, followed by or* pcaute in seven and one-ball hours to quartz dost Microscopic section. At end of 12 months there are nodular foci of extensile ceUula: reaction wttiv cen tral hyaline formation in the lung. Tabis Eett fif ^iumsBUM Confioundt on Trttsfa&Ushtd Siliiotit Lenorts Ke, rrt a* a*i SKH3 6S*-VTf IW! lom-tit fcpofJu et Anfasl Rebbtl a*t*4% Gutee* pig Outoes cte Gejot* pig Bai Aal Xo. < e Method of Prfupulag i/at*Xk l4*tes Ininsresout iMrereocm labtUUoo b latoeletloo & XshtUtSoB a tehillUOfi % Ttmot Bapemre teQuertt irettBctert Tswuseet #*. Sato. Sbr.dtfir tera bo.* Ibr.defiy tors bo. Sbr.dtfir turUase, fir. delir tors are. BSr. a*Py for Stare. AloislBUB Agent s(iJo;M Al{0n> AUOhi, AHOm, AJ(OH), H-JffSO KcUfflc id M*t$0k id enw.iu re After Utlbod Of Trt*aaeBt T*tne(> Mo. RBeotle Tttrue fleet Ub tetr<vcou IS EiJioO latr*enoos u E.fl.4 to 6 tntr*erCleJ It SJ.4 teireeerdlal ' ii EJ.4 lobaleUon tu. 4*Hy ishstettee tt&r.CUU tnOatotteo % far. 441tT IS 2A.4 6 E.S.4 6 Eg. 4 Stovrettoo tr Alesunota XTAtCi ASAiOb X.t.-t A.P.t AP.t A.P.4 A.F.4 *Ta* eXOMnrr Pf tetoelelteo lo test. 234 tfeet u eosfistwd tor aeo'fcrst* tuontO* dutiai traUnset wlte i-->b TREATMENT 0? SJUCOSIS BY MEANS OB ALUMINUM X TH&uKtmc Emcr of Aluuinvk Acsvts ok PSSZSTAMJ9HED gaJCOTXC LSStOWS The next group of seven experiments, listed in Table 8, was concerned with the pro tective effect of aluminum agents adminis tered either by injection or by inhalation to animals which had silicotic lesions in various stages of development. A *group of rabbits was injected intra venously with 500 mg. of quartz particles over a period ol five weeks and then was given colloidal aluminum hydroxide by intra venous injection. The treatment halted an extensive active proliferation. At the end of three months the silicotic reaction had retro gressed to a simple phagocytic reaction re hyaline fibrous siHcotic nodules and the dif fuse fibrous replacing all normal structures except the bile ducts. The microscopic ap pearance of the section from the treated liver was normal except for a localised collection of large phagocytic cells in the connective tissue between lobules and a few isolated phagocytes in the blood spaces (Fig. 6). In another experiment with rabbits, the treatment was delayed until six months after the introduction of the quartz particles. In these animals it was observed that the hy droxide had do effect on mature fibrous nodules present at the beginning of treat ment. but immature cellular nodules re- . ProtectSoo against intravenously administered Quarts dust by means of intravenous a of colloidal aluminum hydroxide. Experiment 77J--rabbits received 500 mg. of quarts particles tor five weeks, followed by 50 ml of AI(OH). for five weeks; result at end I 12 fcooths, Microscopic sections. A, fiver of aluminurn-treated animal; normal except lor small interlobular fod of macrophages. B, liver of quartz control, with confluent hyaline silicotic nodukt replacing all liver cells; bile ducts survive. sembling the effect of a mild irritating silicate, -Such as that of the clay materials. The protce. Hon was maintained for at least one year after completion of the quartz injection. The Kver of the control animals showed massive sili cotic cirrhosis at the end of a year, with marked destruction of liver tissue and re placement by dense leather-like fibrosis. The fiver from the rabbits which received the same amount of quartz particles with colloidal alu minum hydroxide appeared normal except for small areas of pigmentation beneath the eapsote. Microscopic examination of sections from the control liver showed the large gressed and disappeared. Microscopic evidence proved regression of immature cellular nodules. The mature fibrous nodules re mained unaltered. The liver of the control rabbit was completely fibrosed at the end of a year (Fig, 7). In a further experiment to determine the protective: effect of colloidal aluminum hy droxide on a preestablished silicosis, the hy droxide was introduced intracardiaily. Four teen guinea pigs were exposed for six months to a high concentration of quartz dust {<909,000,000 particles per cubic foot of air). Thereafter they were divided into two 235 TREATMENT OR SILICOSIS BY MEANS OR ALUMINUM groups. Eight animals received weekly intracardial injections of 2 mi- of 0.2% aluminum hydroxide without further dust exposure, and six animals received the same treatment but with continued quartz exposure. There were appropriate controls. Four control animals were killed at six months to observe die de gree of quartz reaction before treatment was initiated. Their hmgs showed bronchiolitis, i. e., the stage of dust reaction before nodulation or fibrosis. The control animals which were exposed for six months and then re moved to a normal atmosphere for another six months showed progressive silicosis. Microscopic nodules with hyaline necrotic jection caused retrogression of silicotic lesions that had sot yet reached die stage of maturity, but tissue already -fibrous was not affected. The inhibiting effect apparently depended on the colloid reaching the tissue in the early stages of the silicotic reaction and being re tained either by the same cells that had phagocytosed the quartz particles or by other cells in the immediate vicinity. Chemical analysis of the tissue of the liver and spleen of animals which had received colloidal aluminum hy droxide showed an accumulation of the silica in these organs. When powdered aluminum hydrate H1010 became available, it was possible to { Tig. 9,--Capacity of Inhaled H-1010 altuninara agent to arrest tiUeotis if treatment is con tinued long enough. Experiment 950--guinea pigs exposed foe 11 months to inhalation of quarts dust for eight hours each day, followed by treatment with H-1010 for 13 months. Microscopic sections. A, Jung parenchyma of a guinea pig treated with H-1010. B, lung of untreated quartz control, killed after six months, in which histological reaction shows unintentional protection (see text). centers were seen throughout the lungs, fa the treated animals, nodule formation was in hibited The pulmonary lesions (Fig. 8) still consisted of localized areas of interstitial pro liferation, and there were no metastatic foci of silicosis in the liver or spleen- The hydroxide had not prevented all tissue reaction but had reduced it to a mild and apparently nonprogressive interstitial proliferation. Typical silicotic reactions occurred in the tracheo bronchial lymph nodes. These experiments demonstrated that col loidal aluminum hydroxide introduced by in- introduce the aluminum agent directly into the lung by; inhalation. Twenty-five guinea pigs in which immature silicotic lesions had been predated by previous exposure to a high concentration of quartz dust for 11 months were exposed for eight hours daily over a period of 33 months to an atmosphere con taining an average of 1.57 mg. of H-1010 per cubic foot of air- The treatment was most effective in halting the progress of the silicotic lesions. Mictbscopic examination of the lungs of the four guinea pigs killed at 13 months after treatment showed focal proliferation of 237 - > DWORSK! ^ mononuclear cells only. There was no evi dence of fibrosis (Fig. 9). Analysis of por tions of the guinea pig Jung show,in Figure 9 for aluminum showed the accumulation of 125 mg. of aluminum per 100 gm. of dried hmg tissue- The untreated quartz control animals that had been kept in & norma] atmosphere after their removal from the dust room gave some unexpected evidence of the protective effect of aluminum- Some of the animals failed to develop a degree of disease commensurate with their exposure. Gross examination of the lungs of such an animal killed six months after removal to a normal atmosphere re- that very small quantities of aluminum are sufficient to prevent progressive silicotic lesions in the Kings of guinea pigs. k. tsrscr or AtVMlWUif CoUFOUKDS ON T3E Course or Tvssacutous Inftcttox is Animals Nor Exposed so Quart* Dost Since silicosis Is frequently associated with tuberculosis, experiments were planned to de termine (a) whether aluminum compounds would modify in any way the course of a tuberculous process in normal animals in fected at the same time that the treatment with the aluminum was initiated, (b) whether the aluminum compounds would reactivate a TaplbS.--of the inhalation of Alutnirntm Compounds oh the Course of Tuberculous Infection at Animals Not Exposed to Quarts Dutl4 mm? 406 MMt StfKTV *07 wiA-vui 101* VHB OT6-VUC *r*rU* of Aatael OuIottK* Astatic *>. AJQ&lctfUB Aral B4flW GuteeajK* * B-HOC Oolaea pi* 2$ Uete&ta Ai Oataei pt IS B'1010 Oaiaopkr 9 nwio 16 BMo&U QodMM OaUKspir BtUSM A1 * Ueu&fe M 10l*rra}to. Infection *gdfctPOBM %o Ahmlwm SfriBlUneoa* &oaJUfi*ow SfetSOSUfMOH* o* S*n*o*n* ,to AftA&ium sar,4tflr tern aw. Httr.eanr for U bo. % w. afl tor* bo. (^bO, StfO. SB*. 4tf0. *po. sar.edtv torSflw, Bbr.SQy IcrSjBO- w*r.4j)y lor Uow, ubr.dta? torts mo. Htr. flea* lorU no. Boult* Spn*4tor ti4**Blofe la Sun**, Ub{icS(Uu Woe* rw>f er * SI BbainUoa tsfeetSeo TO nafcnufe fhovwt VJbetotioti* t tf&rt of voioorr,10a no duo* *"******** m?war: &o mcuvttioa OmU&c proceedad no mcevnooo Be*Ha* en*e(Uf erpknBri so reneutnUon BoaSaj uwmM mfeefir; bo reoetfenttoa Setter proeM cjpfcnt; so rurtfotUoo * 0(Tnton umc>, 4tttsB*(d bua& tuber?)* badSot, fltraQs 8); netbod of tofcrUoo, *r IsirafiUdo. vt&fed multiple areas of reaction, but on microscopic examination these foci were not fibrous (Fig. 9). These lesions suggested a partially inhibited silicotic reaction, On ana lyzing the portion of the lung of this animal, it was found to contain 36-6 mg. of aluminum per ICO gm, of dried lung. The upper limit for the aluminum content of a normal lung is 2 mg. per ICO gm. of dried lung tissue, On investigation it was discovered that the quartz dusting room had been contaminated by moving racks of cages from the aluminum room Into the quartz room without first at tempting to remove the aluminum dust that had accumulated upon the cages. Though this development constituted an unintentional inhibitory effect, the incident demonstrated 7JR partially healed or a healed tuberculous infec tion, and (c) whether treatment with alumi num compounds would alter the usual in creased susceptibility to tuberculosis created by silicosis. In Table 9 are listed the experi ments which will be briefly discussed. In the first experiment SO guinea pigs were infected by inhalation of attenuated human tubercle bacilli. Strain Rl. As is well known, this organism causes in the guinea pig a selflimiting tuberculous reaction which heals by resolution or calcification. The group was equally divided. Twenty-five animals were exposed for eight hours daily, six days a week, for one year in an atmosphere contain ing 1.57 mg, of H-lOld per cubic foot of air. The other 25 infected guinea pigs were kept TREATMENT OF SiUCQSiS BY MEANS OF ALUMINUM '* w Pig, 10,--Harmful efTeci of massive atonunom therapy os the coarse of experiments! tuberculosis. Experiment 950-11--simultaneous Infection of guinea pks by means of R1 tuberc!e bacilli and exposure by inhalation to H-IQ10 ahiminum agent eight hours daily for one year. Whole lung sections. A, fang el tainted animal in whkh ooc year ot exposure to H-1010 has resnltcd in massive fibro caseoos tobercukjsis. B, long of R| infection control without exposure to H-1010; standard reaction at end of one year, with minute, isolated, healed tubercles. cellular tubercles in the lung (Fig. 10). In a few animals the lesions were confluent. No necrosis or cavitation occurred. The results of this experiment indicated that excessive concentrations of the alumi num agent exerted an unfavorable influence upon guinea pig susceptibility to tubercu losis. Analyses showed as much as 156 mg. of aluminum per 100 gm. of dried lung tissue. Exposures to this compound in such concen trations ior right hours daily were far in excess of any that would be contemplated for human therapy. Another experiment was riinilar to the one jus! described, except that the infected animals were exposed by inhala* tion to H -1010 tor half an hour daily instead in norms! air as infection controls. In the controls the infection ran a norma! course, healing by resolution, with the disappearance of most of the tubercles by 12 months. The fmdmgs in the infected animals exposed by inhalation to 11-1010 showed, up to six mouths, results similar to the controls. In the 14 animals killed during the 8th, 10th, and )2th mouth after the inhaialwn of H-J0K1, however, all hut one showed some spreading Ptg. ll<--Transitory stimulatory effect of minimal alunuoum therapy on Ri tuberculosis. Experiment 99$--guinea pigs Infected with Ki tubercle bacilli and exposed to H-1010 for half an hour daily. Whole lung sections. A, lung at end of one month, showing a lew small gelatinous tubercles asul asso ciated lymph Qode enlargement B, lung at end of one year; a few calcific scars only may bs found foraltipie dark fod are lymphoid aggregates). Fig. 12,--Transitory tuberculDgtnk effect of metallic aluminum dust. Experiment 101ft--guinea pigs infected with Rl tubercle badlli by inhalation and exposed to metallic aluminum dust half as hour daffy for 25 months. Whoto tong sections. A, lane at end ol rise months, showing multiple spreading tubercles. B. lung at end of 12 months, showing par tial regreoMGPU of pulmonary lesions hot persisting lyrtjph node enlargement 5 of right hours daily. Groups of animate were killed at iutervals extending over a period of 15 months. In the 50 animals killed the tuberculous lesions resolved and behaved in the same manner as seen in the fangs of the controls (Fig. 11), This experiment proved that expolure to the H-1010 aluminum hydrate for haU an hour daily did not retard ibc fcealingjof tuberculosis provoked in guinea pigs by She attenuated human tubercle bacil lus, StrainjKl. DWORSKt Twenty-five guinea pigs were next injec ted with the attenuated human tubercle bacil lus, Strain Rl, and exposed to metallic, alumi num powder by inhalation for half an hour killed over a period of one year. There was no evidence of reactivation. Healing of the tubercles proceeded in a normal manner. daily- Of the 25 infected guinea pigs, 10 showed evidence of spreading tubercles in the lung. The spreading disease was observed in 5 of the 16 animals killed during the first 12 months and in 5 oi 9 animals killed during the last 12 months of the experiment (Fig. 12), Though the spreading disease was not marked and the features of the tubercles sug gested that they would have healed if the animals had been allowed to survive longer, this finding contrasted with the favorable results obtained whs exposure was to H1010 for half an hour daily. The next experiments to be mentioned are also listed in Table 9 and concern attempts to reactivate a partially healed tuberculosis by the inhalation of E-1010 and oi powdered metallic aluminum. The animals exposed by inhalation to H1010 lor eight hours daily for six months were divided into two groups. One group had been infected with the R! strain by inhalation lour and ont^half months previous to the ex posure to H-1010, and the ocher group had been infected six months prior to the ex posure to H-1010. Over the period of six months autopsies of the animals revealed no evidence of reactivation or spread of the tuberculosis. Since it was observed that guinea pigs in fected with the Rl strain by inhalation showed some spreading tuberculosis when they were exposed hall an hour daily by inhalation to powdered metallic aluminum, an experiment to determine whether the metallic aluminum would be able to reactivate an Rl infection was planned as follows. A batch ot 30 guinea, pigs was infected with the attenuated human tubercle bacillus, Strain Rl. The animals were divided into three groups, In the first group the infection was allowed to proceed for two months, in the second group for four months, atvi in the third group for six months before CONCLUSIONS The experimental data presented to this paper warrant the following statements, 1. By injecting into animals a suspension containing both quarts particles and colloidal aluminum hydroxide or powdered aluminum hydrate H-1010, it has been demonstrated that the aluminum agent specifically inhibits the characteristic fibrogenic reaction to quartz. Each aluminum agent has been found capable of completely inhibiting the silicotic reaction for over a year, and there is no indi cation that it would not have continued to do so Indefinitely. 2. The injection of the aluminum agent causes tesolufsoa asd taafog immature silicotic tissue reactions, but fibrous nodules do not disappear. However, further enlarge ment of the fibrous nodules ceases after the Institution of aluminum treatment. 3. The silicotic reaction may be prevented by introducing into the body the aluminum agent and the quartz particles, together or in separate suspensions and by the same or dif ferent pathways, provided that the inhibitor agent and (he quartz panicle localize in the same phagocytic cell Unless such intimate contact is established, protection is slight or absent. This evidence indicates that the suc cessful prevention and treatment of silicosis can be expected only when the aluminum agent is administered by inhalation. 4. Rrophylacrically, the inhalation of pow dered aluminum hydrate H-1010 limits the silicotic reaction lo the innocuous prolifera tion of macrophages in the lung parenchyma, and no fibrous reaction follows. As a treat ment for established disease, the inhalation of H-1010 causes regression oi immature sili cotic lesions, but its only effect upon fully developed fibrous nodules is to prerent their further enlargement and their confluence. the infected animals were exposed half an hour daily by inhalation to powdered metallic aluminum. The animals in all groups were 5. Normal animals, repeatedly receiving the aluminum agent by injection or by in halation, show no evidence of any toxicity or 240 TREATMENT OF SILICOSIS BY MEANS OF ALUMINUM \ of aoy chronic change that appears to affect their health. The agent is ingested and re tained for at least one year by connective tissue phagocytes. The metallic aluminum agent elicited the least cellular response. 6. The inhalation of excessive amounts of jfowdered aluminum hydrate B-iOlG for eight hours daily for one year transiently causes extension of the tuberculous process in some animals infected with attenuated human tubercle bacilli Strain Rl. The spreading infection does not, however, cause death. When the animals are exposed to H-I010 for only half an hour daily over a period of fifteen months, the hydroxide ap pears to have no stimulatory effect on the benign course of this type of tuberculous infection. 7. The transitory stimulatory effect of inhaled powdered metallic aluminum on the tuberculous process lasts somewhat longer in comparison with that caused by colloidal aluminum hydroxide under the same experi ment conditions. REFERENCES 1. Gardner, L. U.; Dworskt, U-, and DeUham, A. B,: Aluminum Therapy is Silicosis: Experi mental Study: Donald E. Cummings Memorial Lec ture, J. ladust Hyg. & Toxicol 2ft:2U, 1944. 2. Kettle, E. H-: Interstitial Reactions Caused by Various Dost* and Tbrix Influence on Tuber culous Infections, J. Path. & Bact. 12:39$, 1932. 3. Denny, ). J.; Robson, W. XX, and Irwin, D. A.: Prevention of Silicosis by Metallic Aluminum, Canad M. A. J. 27s 1, 1937; IS;2l3,1939. 4. Gardner, L. tl, and Rediin, A. J.: Sig nificance of Chemkal Examination in the Diagnosis of Silicosis, J, indust Hyg. & Toxicol. 24:125, 1942. 5. mifcy. G. F,; Hawley, J. G, and Wright, C. W,: Toxic Properties of Silica: Bronchoconstrictor Effect of Colloidal Silica in Isolated Per fused Guinea Pig Longs, J. Indust Hyg. & Toxicol. 27-.37, SW5, 6. Scbeel, L- D.; Smith, B.; Van Riper, j. and Fleisher, XL; Toxsaty tA Silica: XI, Characteristics of Protein Films Adsorbed by Quarts, A. M. A. Arch. Indust Hyg. 2:29,1954. 7. Schepers, G. W. H: Cyu&otogfcal Mani festations of the Surface Properties of Quartz, A. M. A. Arch. Indust. Health 12:266-275, 1955. 8. Gardner, i- U.: Studies q Experimental PneumonokomosU: VIII. Inhalation ol Quartz Daft, /. indust. Hyg< 24.-12, 3932, / \ 241 1' Experienced with the donlroi o^ jSilicodh in the Eeramic +3^ndudtr 0. L fFRRY, M.0^ H CaMte, H- in the raw materials, and this fact may have significance, because experimental work has shows1 that soda ash increases the solubiHty Silicosis of varying degrees of seventy has been encountered sporadically in the ceram ics industry. I have been associated for about 12 years with such a plant which has been manufacturing bathroom fixtures since 1907,; A study of the influence of aluminum therapy on the course of silicosis was facilitated by the fact that there was a very low turnover in workers- During the first 25 years of the existence of file plant, no connection between the ceramics industry and silicosis wa recognised by management. Consequently no attempt was made to keep the plant dust-free. Silicosis first became recognised m Pennsyl vania as a compensable disease during 1937, Since that time strenuous efforts have been made to clean up the plant. Dust levels aver aging less than 5,000,000 particles per cubic foot (ppcO have been achieved in the casting rooms, with a range of 800,000 to 4,100,000 ppcf, It has not been possible to maintain such levels in the mixing rooms, where lim and subsequent toxicity of quartz. Clinical studies of casting department em ployees in the ceramics industry, as a whole, have demonstrated fiat, in spite of dust counts averaging below S,000,000 ppcf, from 40% to 50% of the casters have raiological silicosis after 12 to 15 years of exposure. As the dust counts are low, the statistical finger of guilt points to the soda ash that is admixed with the silica. In my experience and that of other physi cians * concerned with the ceramics industry, the radiograms in ceramics workers are best classified as follows: Class I: Normal chest O&ss I1A: Increased lung markings bat still within normal limits Class 118: Compatible with inripkmt silicosis Class III: Nodular silicosis Ow* IV: Coaksccm silicosis Class V; Complication ited numbers of personnel have been obliged to handle raw clays, flints, and feldspars. Because of the fact that the majority of employees work m the casting department, the greatest hazard, from the point of view In grading the various cases, several groupings of the above five classes are pos sible, e. g,, IIA -fV or Ill-fV. The classes do not necessarily correspond to the degrees of associated disability. of statistics, remains here, even though there I have dealt with 139 ceramics workers is excellent ventilation and at points where continually during the past 12 years. Among dnst is generated respirators are provided these, 36 cases of indisputable silicosis were Cor the men. The respirators ate not always identified, the dominant lesions being those in use. Soda ash is employed as a defioccu- graded as Classes III and IV above. Two lent. An incidental effect of this is that the cases only of active tuberculosis were iso soda ash increases the solubility of free silica lated. Thirty-two men were it) Gass IIB. Rseordtd for publication JuIf S, 1955. Medical Director, Univei^al Ruridle Corj>. 242 Hannoo, J. W, C,, and Boxrd. P. r Personal communications to th autltor. CONTROL Of SILICOSIS IN CERAMICS INDUSTRY in 19*4, after two successful claims for occupational disease brought against the company, it was decided to treat the men by aluminum therapy. At this time dust counts over the entire plant were found to be below the legal occupational hazard level, ex To assess the influence of aluminum is the control of sjlieosis in this ceramics industry, the foliowing criteria were applied: (a) symptomatic improvement, aggravation, or stasis; (i) radiological progression, arrest, or regression. cept in the day-mixing departments, and have been kept so during the whole past decade. All employees were given the opportunity to take treatment at regular intervals and in Of a total of J39 men who received aJu* roinum therapy for a period of 10 years, the results were as follows: deed were strongly urged to do so. No one was discharged because oi failure to use treatment. The method of administering alu minum was technically identical with that described by Osmond.* The regimen of CftKS (*t B*&9toja*t}e Bw&co/.................................. . ?3 ............ H> Jnj>fOT*................................................ a Worn............................. -....... 8 therapy, however, deviated from his method in minor respects, owing to special environ mental circumstances, Sixty-five per cent of <&} EftCtcJoifefti MM*.......................... m DnrtioiBd......... ........................m Inpreiad................. Pro(t*aMd........ . i all the men in the plant received constant aluminum therapy for the past 10 years, i e., they received five to six minutes of aluminum powder inhalation once a week during the whole yeas. A total of about S650 mg. oi aluminum oxide powder per man per year was used- Another 25% of the men received sporadic treatment; i. e,( owing to illness, absences, and lack of enthusiasm, they missed many of their scheduled treatments. When the company first started to administer alumi num therapy, the men were put on frequent intensive courses of therapy,with intervening rest periods. After one year, however, it was deemed advisable to institute constant ther apy at weekly intervals. AU the men with a Thus it appears that aluminum has a markedly beneficial effect in suppressing symptoms and in arresting radiographic ad vance of the lesions of the men subjected to study- For instance, of 73 men who had symptoms at the start of their course of therapy, 62$ were improved at the end of 10 years, while only 54$ showed no ameli oration and 4% became worse in spite of therapy. RadibtogicaUy the following results were obtained: Of 139 men who started aluminum therapy in 1944, 84% remained unchanged, 14% improved, while 2% progressed. silicosis classification in Grades 3 and 4 re ceived two or three treatments per week, totalling 600 to 700 minutes of therapy per atmom as against an avmgc of 250 minutes for those without silicosis or with incipient lesions only* As an additional aid in selected cases, 1 have, since 3950, used intermittent positive-pressure breathing administered by means of the MSA Pneumophor. Phenyl ephrine (Neo-Synephrine) hydrochloride COMMENT ft was not possible to have adequate con trols in this study because of management's desire that all employees should undergo aluminum therapy. The untreated group represents the employees of Jess than !0 years' work history and does not constitute a control group for the 10-year period. Many of these men entered the service of the com and Alevaire were introduced into the pa pany dutrhg the last eight years and hence tient's respiratory passages by this means im do not fulfill the requirements of this study. mediately prior to each aluminum treatment Others left the industry during this period, session. This method was resorted to in all and thus their cases have no statistical im men with advanced silicosis or with marked portance. The only control resides in the symptoms. experience of the company management in 743 PERRY respect of the numbers of key and skilled men that were conserved after the period of alu minum therapy had been instituted as campared with the disturbing personnel losses annually experienced prior to this period. This improvement was also reflected in re duced disbursements for disability compen sation. Another corroboration of the value of the method comes in the form of sustained enthusiasm by the men during the whole 10-year period and insistence on the part of the labor union that therapy must be con tinued. suumasy One hundred thirty-nine employees ot a ceramics plant with a known alicows hazard were subjected to aluminum therapy for a period of 10 years. The average amount of aluminum used annually for the employees without advanced silicosis approximated 1650 mg. per case. Silicotks in the more ad vanced stages received up to three times this amount at the start of treatments. The aluminum therapy appears to have an indisputably beneficial influence in suppress ing symptoms, in arresting radiological advanct, and in improving the functional re serve of ceramic workers. REFERENCES 2, Denny, }. Robson, W. D, aM Irwin, D. A,: Prevention of Silicosis by Metallic Aluminum, C&nad.'M, A. J. ttsl-U, 1937. 2. Osmoud, L. H.: Experiences with die Centro) of Silicosis in a Foundry, A. M. A. Arch. Indust. Health 1*:221-22$, J9S5. 244 * > So*. tit Siiico&iA (^ontroi xperienceS wi QJd mining m X K, GODIN, M.L, 8llt<rrc, Qe*,, Coaeda h)i*i5">'r4*';'*~B>iSUieifc'rer,Si',rrmr<'i*Ti This paper deals with silicons control measures and experiences in the gold-mming industry of the Province of Quebec where there are 16 straight goId-producing mines. AU at* located in the northwesters section, in the counties of Temiskaming, RouyoNoranda, Abitibi-East, and Abitibi-West. These mines handle a minimum of 4,500,000 tons of ore annually. The free silica content of this ore averages 70^. Of a total of 4150 employees, about 2900 are exposed to siliceous dust. CONTROL MEASURES In general, the control of silicosis has received in the gold mines of Quebec the attention* which it warrants. The principal control measures are the following: medical supervision; ventilation; dust control, and aluminum powder prophylaxis. Medical Supervision.--As required by the Quebec Mining Act, every employee in the industry most have a medical certificate, issued by medical officers appointed by the Workmen's Compensation Commission, which certifies that the applicant is free from diseases of the respiratory organs. Annual control examinations are also man datory and necessitate issuance of a certificate which is renewed only if the employee is free from tuberculosis of the respiratory organs, Recorded for publication July 5.19S5. Manager. BeSfete/re Quebec Mines, limited, The results of the annual examinations are made available to the employer concerned. This is a great help in prevention work in that any employee who shows a predispo sition to a lung disease may be placed in a nondusty occupation. Many of the mines required pre-employ ment and annual control examinations with chest x-rays even before such examinations with the accompanying certificates were re quired by law. When medical control became compulsory, workmen already employed whose chest x-rays revealed some abnormal condition, varying from slight fibrosis to some degree of silicosis, were given restricted certificates which enabled them to continue working at the mine where they were em ployed at the time of the certification. These mm either were advised to leave the. industry or were transferred to nondusty occupations. The solutions to some of the problems en countered were described at the 1952 Con ference of tiie McIntyre "Research Founda tion by Fisher,* Ventilation (Consult also Appendix A).-- Adequate ventilation and dust suppression arc primary factors m the prevention and control of silicosis. Ten of our sixteen gold mines lave mechanical ventilation systems, while the other six are ventilated naturally. Most main fans are placed on surface, and special permission from the Department of Mines is necessary for the underground installation of a main fan. A shaft usualiv provides the return air circuit, especially at the smaller mines. In development headings and isolated sections, auxiliary ventilation Fisher, R. S. M.: Examination, Practice, arse? Experlences'Regarding Compensation and Certifica tion, read before Use McIntyre Research Foundation Conference. Noranda. Que., .fan 28-30. 1952, 245 t GQ&H supplied by small compressed air or electric fans, exhausting or blowing through metal or rubberized tubing, Great concentrations of injurious dusts are generated by blasting operations. Danger from this source is minimized by the feet In the mechanically vcntilatetf mines, the that before meo are allowed to return to air circulated in one day averages 50 cu> ft/ the scene of a blast much oi the dust per minute per ton of ore mined. Air circula suppressed or removed. Water sprays are tion through stoping areas varies between used for such purposes throughout the 00 and 4000 c. t vet., the average being industry. A mUt-Uke spray is produced 1 SCO to 2000 c. f.m. through a combination of compressed air and The Department of Mines employs two water. The sprays are turned on at Wasting ventilation enginms, one stationed in Que time and are left v operation throughout bec City and the other m Noranda. Them the interval between working shifts, a period duties include conducting periodic surveys of from three to eight hours. The water of the ventilation and dust-control systems spray imniratats the dost produced by the in underground workings and crushing blast, wets the walls and muck pile, dissolves plants, making recommendations following nitrous fumes, and humidifies the air. Miners these surveys, and conducting follow-up are required to further wet the working lace, surveys. They are svaikbk also to assist walls, and muck pile with a standard water in solving specific ventilation problems. hose before beginning work in a freshly Some ol the larger mines employ their blasted area. own ventilation engineers. In such cases the Drilling operations underground are government engineers verify the surveys further sources of dangerous dust concen and systems to the satisfaction of the Depart trations. Although the concentrations arc ment of Mines. ordinarily not so high as to some other Dust Ceniroi,--Primary crusldng is done underground at many mines. This operation produces the largest dust concentrations that underground nwn must breathe. 3*or maxi mum protection, good exhaust systems must be used and the dust-laden air removed to return air currents and oat rcctccutated. 1-argc and dangerous amounts of dust underground jobs, more miners are sub jected to the dust during the whole drilling shift. Wet drilling is universal practice. Most mines require the automatic air-andwater throttle, which makes it practically impossible to start or drill a hole dry. The vented front bead and oversized water tube are also in common use on present-day drills. Ore pass dumps and drawpojnts are are produced in underground scraping and slushing operations.!1 To keep dost counts al a minimum, the muck is continually further dust-producing locations. Most dumps have doors that are kept dosed except when a train of cars is being dumped. This wetted down daring the working shift. This keeps the dust out of travelways. Water is complemented, especially in scram drills,! sprays have been tried at drawpoints bm by a good ventilation system. proved unsatisfactory. Ore drawn from t Slusltmg U a method o( mfichwdcal loading cl ores.. The scraper or slujher carries the load. I* is pu/frd by a single drum hoist, operated by one mar. Another man guides (he jlnshtr and pulls It back to The face. Scraper loading employs a two-drum hoist, the scraper being pulled back to the face by a cable tVi/ouch a fixed tall sheave. Only one man is needed. t A scram drift is an opening in a slope above the main haulage drift, generally at a right angle to ft, whose purpose is to provide a passageway for ore from 'he slope * the haulage drill stopes is ordinarily moist Underground samplers wear dust masks while cutting samples. Cutting satrapies Is a procedure for taking a representative portion from a whole material for assay purposes. Underground, a sample is cut across a vein or ore fees. a mott and smgle jack hammer or more simply by means of a small hand pick. In a laboratory or assay-office cutting, a sampk would entail putting crushed material through a sample splitter, which mechanically cuts a repre sentative sample of the whole. 2r. S/UCOSPS CONTROL IN GOLD MINING Surface crushing plants are also sources of large quantities of dust. Most plants have satisfactory exhaust systems which remove the dust-laden air from discharge ends of crushers, from screening floors, and from ore transfer points. Assay-office grinding rooms are equipped with exhaust systems. The operations which produce Hrrdesfrafefc dust concentrations ate crushing, riffling, pulverizing, and screening. tains a high percentage of free silica, the average is below 5,000,000 ppef. Dost con centrations increase with the rate of mining in a given area and the tonnage of ore and waste handled. The dust counts that have been most frequently met during mining operations are given in Table 1. For pur poses of comparison, the base metal mines oi northwestern Quebecare included in these figures, showing that some of these ores Ta& I,--Average Dust Counts in bftuti Mints ej Northwest Quebec Operatic* rwaai ontor DffBtef Vtttbr Wnttt&f Screptef nr abates Senpt&f 0r ahufeWs Berapbf or tfaehbf SouBi or ibnUst CSrcfe paJBa# Chete puStof QtuW pUEtef Quite bUttis* flirnnlitr braaklei 8*eo*drr feraaktof Uadenrouad trewsta* Dodergreosd tnufcfog Under* enaablof B*tp tester k5art.be dritu L*r**ra and eir-kf anik fiimn Socket &vtt Const, lU> tJt e.OtoSBA >04 94Ur *4 RoAtl ifiiOTCl Ait dotber Ate liusbtr Shctrie abater EMHr (teaser SAW IfcO lute .9 10 to ISA auto ia auto tac Jlasctoperatod **tea Arafate ot abate*at* e&utai Arc&i or eb*te-rU Saict , , (m6ii bHrtt' , . (laBd&lette) tau> *s> jut so OpU>A aute taw mu w to *04 Ji enit&fr 1.0 Jaw ayoaber WA to ISA Jaw ember eerwutoW Meaeurter pocket 10 to wu OoBuaUBUi Hok* eoUerad rut m&4 drilled wet is drift* IU>a atopaa Botaa eoBarwl dry tor a ten aacoadsi took 01 adedoate prewar* Holw jaseraBj 3rad dry; fasptee takt* Muck 9<rt; *Jmpl taka# a M!t becJtset end drewpoBat* &7T on or vast* Or or vwte kept wet Dry seek Or a5si; (topee wafl eanUJated r>T7 or or aiit; bt*b Nuiita srodood ts pte ot food vcBURtloP Or* tsotat Ora notet Vary dry or Staple* Uka aboat t mSs. after bUn Is vali-vastftMad frtnR drift* tad acraa Oelltt otter taotc iad ekararf away la cmelra stead eskauatad ires grintt or !e eruabbf roes* food duittoQactter cy*> tea: asbaeet piped to toeJt; extent** ate babe rUod bj Irmj aJr ZteflwoOeettef Bycus bat exteoat ir ra- Witkout asp durKoUwtiJK eryetea; wr oost ofrtapsed wuk very wot or Lose; eoeut otnjetd {q wit ora eM aood tJ/eft tbroofb ioadiar eta (tea In taking dust samples, the Department of Mines engineers use the midget impinger, Tite samples are counted on a microprojector at a magnification of X 1000. There is no acid treatment given to the dust samples; &o all the dust particles are counted. The maximum allowable concentrations are 5,000,000 particles per cubic foot (ppet) of air for dust with more than $0Jo o free silica and 10,000,000 ppcf of air for dust with less than 5O5& of free silica. Underground dust concentrations have varied from a low of 600,000 ppcf to a high of 75.500,000 ppcf, the average being about 7.300.000 ppcf. In mines where the ore con- have as high a free silica content as the gold ores. Mining methods used are much the same. The dust counts in naturally ventilated mines were not higher than in the mechani cally ventilated ones, probably because min ing is done at a slower pace. However, traces of carbon monoxide can often be detected in the general atmosphere of the naturally ventilated mines, especially during the sum mer months when natural ventilating pres sures are Qften negative, In crushing plants the lowest dust count was 600.000 ppcf of air. and the Highest 247 GODIN Fig. I.--Pbpersaj of ahtnutum powder by compressed air Rector* in rmne-ciotheg sec<wn of chartgcfaouse. was 106,000,000 ppcf. Crushing plants with \try good extauA systems have less than 3,000,000 ppcf of air in the general atmos phere of the plant during the summer months and less than S.COO.OOO ppcf during the winter months. Dust counts are always higher during the winter months because windows and doors are kept closed. They are higher too when the ctutfctag machinery is first started and vary according to whether the ore is wet or dry. Crushing plants with poor exhaust systems have counts ranging from 10,000,000 to 20,000,000 ppcf of air Vn the swantt to 4O,C0O,CiCO pped or more in winter. In these plants the employees are required to wear dust ntasks until recom mended improvements are made. In mills dust concentrations are usually well below 5,000.000 ppcf of air atid do not present any hazard. In assay-office crushing rooms weli-derigned exhaost systems keep the dust counts below 5,000,000 ppcf of air. However, if the employee is careless in cleaning pulverizers by means of compressed air jet, the count may be raised to 20.000,000 ppci of air. Since the dust-producing work lasts for only an hour or two. rhe employees wear dust tnukv 24g Aluminum Powder Treatment.--Even with good ventilation and dust-control sys tems, not all harmful dust is removed from the air that rmne workmen must breathe. For this reason, 12 of the 16 gold mines are today using aluminum powder as a prophylactic measure. A minimum of 2900 ^ Fig, 2.--Devke lor measuring powder concentra tions used in aluminum powder treatments. t SILICOSIS CONTROL IN COLD MINING Taj* i^Siticosie Cases Compensated by tbs Quebec Workman's Compensate* Commission IPS1-19S3 Jadustry OoM Calais*...,............................. BaeecaeUJ mining........................ XXUSOM draft*............................ OUxa .................... ....................... PerOnt Cwee, at Vo. Total i Si e Tprp .--Gcld*Miaing Silicasis Compensation Cases: Living Miner* g{r 0! Siikosii PriBirr iScoua.............. Bcee&tUjy tUtecxBa........ CoapBeitttt afflanU*..,. itnsit Age Wbea decease Core- Expo Ooses, Scouted, sure, Ho. Sr, a.t ns * UA ns 1 3> us men are employed by these 12 mines, sad all who are exposed to siliceous dust in their work receive the aluminum powder treat ments. cases are now deceased; particulars are given in Table 3- Particulars oC the il living cases are given in Table 4. Table S shows the years in which 20 cases were recognised as claims. The atumlseffl powder is dispersed by compressed air ejectors >a themme<tehes section of the chaagehousc, as shows in Figure i. A disciiarge pressure of about 40 lb. per square iach U used, correspond ing to a line pressure of ICO Ih. Windows anddoors are kept closed during the dispersal phase. The powder concestrstion recommended is a Bomtaum of 20,000 panicles per coble centimeter for a 10minute mhaiatwe period or 20,000 particles per cubic centimeter for a 20-minute session. The powder concentrations are measured by means of a filter-paper samp'er calibrated against the thermal precipitator (Fig 2). The basis of disposal is t gm, of powder foe each SMb cu.h.ot room con tent where the average period of exposure to the powder is Id minutes. If the exposure period is to be 20 statutes, the amount of olunsimsn to be used is halved. Treatments are usually given who* the workmen are cowing on shift, but in some cases it has been found more satisfactory to administer the aluminum as the men come off shift. Disability in these cases has varied from 159& to lOO^fc. Applicants for pension are referred to the Silicosis Referee Board of the Workmen's Compensation Commission by the local examining physicians. The proce dures of this Board in examining claimants and establishing the degree of disability were described at the Noranda Conference of the McIntyre Research Foundation by Dr. Vidal,|| the Chairman of this Board. aois op xu?inxtm i smecKi* PREVENTION Because of the policy of management to attempt to suppress dust by every known or possible means, it is somewhat difficult to formulate a statistically valid indication of the specific role of aluminum in the control S1UCOSIS RATES From 1931, when silicosis was first reeogmzed as an industrial disease in Quebec, until 1953, the Quebec Workmen's Compen sation Commission compensated 230 eases, 116 cases being complicated silicosis (tuber culosis present) and 114 cases being un complicated silicosis (Consult also Appendix over the silicosis hazard. The working force is over 4000 men, and about 2900 of these are exposed to siliceous jj Vidal, J. A.: Examination Procedures for Silicosis as Practiced by the Workmen's Compensa tion Comnu*on of Quebec, Canada, read before the McIntyre Research Foundation Conference, Nor- *nd>sQ.f 3>.2S-3M9S2, B). The distribution is sltown tn Table 2. Nine of the twenty gold mine compensation Table 5.--Tears When Gcld-M\ni*f} Compensation Cases Were Recognised Tajsu: 3.--Gold-Mining Silicons Compensation Case3: Deceased Miners Year T i Casa, no. JNl ... Tear Cam. Mo. ' St*of611ie06ij Owotn*Ue*tl sTJ*Ss.. CcotplieaUrt *flJeel*. Osses, No. 8 1 Average AC* at Death. Tr. NO 60.3 Averse* Expo sure, Sr. 17.0 384 ise___ 1817,... 1 8 GODIN dust. To date we have had 20 compensation eases of silicosis. It is impossible to estimate how many men working tmder-restncted certificates will eventually become claims. Undoubtedly some will; njany will not. How ever, from the resets 10 the present time, it is evident that the control effort has been worth-while. Since 1W7, the sharp decline in new cases of the disease in Quebec gold mines has been intriguin^y coincident with the genera! adoption of aluminum powder prophylaxis in this industry. No other method of control was introduced at that time whkh caw satisfactorily account for this change. A review of the problem at a later date may clarify the whole issue. Meanwhile, how ever, personal conversations and correspond ence with the other gold mine managers in Quebec have confirmed the general convic tion that the beneficial influence of aluminum powder has been sufficiently impressive to continue its use. No ill effects have, more over, been recorded from the aluminum exposures. For assistance received In (he preparation of this paper, I express my dnetre (banks to the following: Mr. Eugene Larochelie, Secretary-General of the Quebec Metal Mining Association; Mr. W. O. Lafotmirw, Assistant Chief Inspector of Mines for the Proving ol Quebec; pr. J. E. McArthur, MetfeaJ Officer for the Quebec Workmen's Compensation Commission, and the nine manages of the go&d and: tase-metal mines of northwestern Quebec AFPBN&rx A be provided and kept in operation until stidt work ings have abandoned or ootil satisfactory natural ventilation shall have been brought about therein. Safety and Sanitary Precautions Ail buildings must be boils aud kept ifi such a manner as to secure the safety oi employees and stall be well lighted and ventilated. The operator shall cake necessary measures to insure removal of noxious gases and dusts. Atasks The operator must supply to workers masks of a type approved by the Minister and designed to protect workers who are exposed to dust, gas, and irritating and dangerous fumes. APPNDfX B Extracts raoa the Quebec Wo&jck&k's Com- VENSATttM* Act 106. In thH act, 1. ) the word "pneomoaNUosfa" stall mean a pathological condition of the lungs, due to breathing air containing siliceous dust and characterized anatomically by generalized fibrous changes in both lungs; such word includes, especially, the diseases known under the names of `'silicosis'* and *asbesttsis." 2. ) die expression "siliceous dust" shall taeao silica dust or other eompotmds of silicon, including asbestos. |21 Geo. V, c. 100, s, 205a; 2 Geo. Vf4 & 85, s. 5; 7 Geo. VI, c 27, s. 6.J 107, In order that "pneumoconiosis" may be eonsidered as industrial disease within the meaning of this act, the workman most hate been actually ex posed to the inhalation of sSicecos dust In tbe course of bis employment m the Province, during periods the total duration whereof amounts to at lout five years. |21 Cte. V, c. 100, s. JOSb; 2 Goo. VI, * 89. s. 1; 7 Geo. VI. c 27, s. S.J Extracts ntoar RigiT-attons rce me Safety and PaorECTTOK Of WORKMEN t Mj*E5 AND QtfAJt- Jttss, Estasjsbed r Oax*a-sN-CouNciL in VmrvE or the Quebec Mjhikc Act Ventilating Fans' All fans except auxiliary fans shall be above ground and shall be reversible and all fans and structures containing the same stall be fireproof, Fenttiatb* ol Workings Tfte ventilation fa every mine shall be such that (he sir in all its workings that are Jn use or are to be osed by workmen stall be free frost dangerous amounts of noxious impurities and shall contain sofficaent oxygen to insure die health of anyone employed in say such mine, in any mine workings where such condition cannot be obtained by natural ventilation, means for mechanical ventilation shall DISCUSSION On Paps&s ay Me. Dwoasat, Da. Ikwin, Db. Gskono, Pem.y, ao Us. Gtsvm ProphylBsb end Tkeropj1 ef Silteesk by Mee^rt of AImIiwb Da. Pas. G. t have been particularly interested In silicons for three decades and became interested in aluminum therapy about 1944. During the patt 10 years, l have thus tad an oppotYoraty of watching x-ray films of some 4000 or $000 persons exposed to quartz dust, some of whom have also been tmdef traatauot by means oi atardnufu ther apy. 1 have found a decrease in the rate of progres. sion of silicosis among those who have been treated with aluminum powder. I think that this is an wtes* esting and a prophetic thing to find after such a brief study, as it takes from 25 to 3d years to pro- 250 t SiUCOSIS CONTROL JN GOLD MINING tla silicosis. Tbc statement from Morris Dwor- mains in doubt is whether the results of experiments skfs discussion which impressed me most particu with guinea ptga may be extrapolated to man. The larly w* that possibly aluminum compound* are ' clinical reports by the McIntyre Fotsdation on the good for more titan prophylaxis, sinre they help to prophylactic ase of alumtiuzm have all been favor eliminate the immature nodules in the established able. They have, however, had the Haw that no case of experiments! silicosis. proper central* were set up, and there are some who Da. T. L Shipman : Have there been any studies in which a group of men receiving aluminum ther apy were paralleled by a control group in the same industry? Dk L y, D, Osmond: I do not know of any such studies, We have a potential control group in this pUfit, and I tried very hard to get five or six men in for lung function studies. They were not available. Dk. John Summers: What type of pulmonary function apparatus did you use for your lung func tion studies, and what kind of intermittent positivepressure machine? Da. F. Gascons: We followed the standard methods evolved by Sr. George Wright, of Saranac Lake, is bis studies on the pulmonary disability of the pneumoconiosis and placed greatest reliance on reason that the simultaneous improvement is in dustrial hygiene in the plants where aluminum was introduced was tin cause of the improved silicosis statistics. This confusion of issues is regrettable. The problem could have been solved ut South Africa, where excellent control facilities could have been established, but South African authorities were prejudiced agal&st the method by the pre mature criticism which emanated from Canada and the United States. Twoof the main objection* which have bees raised against the employment of alumi num have bees that ft sight facilitate the develop ment of tuberculosis and that the aluminum dost may itself cause a pneumoconiosis. There is oo eHnkal proof that aluminum provokes tuberculosis when used as a prophylactic. Tubercu losis rates xd Canada have gone down, not up, in spite of the ase of alaminom. Those who use the the blood gas levels at rest and cm exercise. We also method would surely cot be so callous as to continue studied the limits of the capacities of the men to to use it if they suspected that it provokes tuber work and compared this capacity with the pre culosis. The Saranac Laboratory has shown that dictable capacities of norma! men. We also evaluated the peccnUge improvement of the vital capacity, maximum breathing capacity, and also arteriolar overwhelming exposures to aluminum hydroxide and metal powder, probably by lowering tisaee re sistance, mildly activate tubercle bacilli of the Mood gas changes when the subjects breathed oxy attenuated R* human strain found eminently suit gen while performing work. able to probe the capacity of inhaled dust to facili Da. Kazj* Jo$g*e: What dees aluminum and tate the development of progressive tuberculosis. prevention therapy cost a company, and under what The lesions resulting from such concurrent ex conditions may one use the method? Da. J. W. G. Hahhon : There ate one or two requlrtmeots that must he falfilled before a company can ase ahamnam. First, it must be proved that management is making every effort to reduce the dost 4 the plant to the practical working minimum. Second, there must be a medical control program. Third, there is a licensing f of $i.00 per year per each man who is exposed to quarts, These dollars are paid to defray the expenses of the McIntyre Research Foundation in administering the patent, and any surplus must be dedicated to further re search ut industrial pulmonary diseases, tiud of which is silicosis. M*. T. C. Wxtat: I'd like to ask Dr, Scheper* whether or not to Us opinion as of this time the use of aluminum therapy either inhibits or retards the development of siiieosis, whether it is safe to em ploy, and whether this type of expedient may be the ultimate solution of the problem of silicosis. posure to aiamioum dost and infection by R* baaHi are transient and probably amenable to present-day therapy and therefore very different from the tuberculosis which complicates quart* ex posures. Moreover, the tt&erculogemc propensity only showed itself when experimental exposures to aluminum were excessive. Wften used io amounts comparable to tl* quantities to which the men are exposed for purposes of prophylaxis, die aluminum does not activate tuberculosis. We do sot know much about the so-called clinical cases of alunucosls. Their occurrence has been limited to but a few German wartime industries. The pulmonary lesions may have been due to con taminants of aluminum, as, for instance, stearin, No disease of comparable nature has been caused in animals. ^ 1 could not say whether aluminum is going to be the ultimate answer to the problem of silicosis. The first and most important method of prevention re mains dust control combined with proper medical Dt G. W. H, ScHsnas; The Saranac Labora supervision. But tthere are certain circumstances In tory has already produced conclusive experimental which qoarta inhalation cannot be avoided. As tpe proof that in some forms aluminum is an elective have pritna-fade evidence that aluminum can pro prophylactic against silicosis. The issue that re tect animals from the effects of quurti and as we 251  y.*' GODJti have no adequate reasoo to suspect that aluminum in the recommended dosage eu cause harm, why not at least try it in cases of jilkosissJvliile we know of nothing else that can serve as a certain prophylactic? Certain exceedingly dangerous quartz derivative* and amorphous silicas have also found their way Into the modem industrial environment, Means must be found to protect personnel against iftdf deleterSous effect, and, U engineering canto* but aluminum will do so, we have at least one method to try. M*. T, C Watbs : Are the benefits reported by patients on aluminum therapy not merely psycho* logical? Dr, G. W. H. Scsei'Eas: Psychological support ts a most valuable adjunct to any form of medical treatment; indeed, it is an objective of medical ther apy. Men who have been exposed to aluminum re port rspjd and marked improvement in weil-belng. It is possible that this Improvement may be imagi nary. It is equally possible that the alwninum helps to ecuatcraet the toxic action of the aasmukVed quartz. The experiments of Berry and Christie purporting to show that psychological improvement cooitastes the only beut to fee derived from aluminum therapy are not conclusive, as they did not prove that their control substances were them selves pharmacologically inert. The resistance to the concept that alamsotun may help as s tirerapeutic agent stems naturally from the apparent permanence of the mature nodule- i do not believe aluminum can take away eoftagenous nodules. There is, how ever, much more to silicosis than the mere de velopment of nodules Prolonged Quam inhalation leads to bronchitis, emphysema, arid pulmonary vas cular disease,. Sven though alucfcnum cannot re solve collagenous nodules which have already formed, if it can but alleviate brooehitis aud. esttphy* Serna or prevent the supervention of cor pulmonale, while retarding the formation of new nodules, its introduction will have been of great benefit to the employee. After all, except in the more advanced stages, the silicotic is not disabled by tire nodules in his lung but rather by the abovo-meooooed func tional metbannms, which are so a measure reversi ble aod therefore amenable to therapy. 252 * {Reaction C^ltromium (Compounds with $o<ly ^Jt6Stie6 anJJLif (lon&litnenfa K M. lASTI#, Sc,t>. C M. CAM*ON, n.o. i. H. CURK, 9tf4 V. BUDACZ, Ph.O,, a,Wmwe Epidemiological studio * have shown that the rate of bronchogenic carcinoma is sig nificantly bight: in inem who had btsn ex posed to high concentrations of chromium compounds In the chromate-chemical mamifactoring industry than in comparable control gfoups. In order to study the possible role of chromium compounds in lung cancer, two types of investigations were undertaken In this laboratory: (a) studies of the incidence of lung tumors and other pathological changes In several species of laboratory animals upon exposure to chromium compounds and ($) chemical studies on the distribution of chro mium In men and animals following exposure to these, chemicals and the reaction of these compounds with body tissues and their con stituents. The preliminary results from the lung tumor studies were presented at the Sixth Saranac Symposium. The preliminary results of the biochemical studies will be re viewed in this presentation. The data are not complete because the experiments are still in progress. Recorded for puMkadon June 6, 1955. Department of Environmental Medicine, Seispol o? Hygiene and Public Health, The Johns Hopkins University. This investigation was supported by Research GranI C-6G3 from the National Cancer Institute of the National Institutes of Heahh. Public: Health Srrvi. * References ! to 5. The cancers which have occurred in the chromate workers have been located entirely io the respiratory tract. As far as is known, cancers have not occurred in the skin or nasal septal membrane of these workers, although skin ulcers and perforation of the septum are very common in persons exposed to chro mates. Cancer of the gastrointestinal tract also "has not been reported, although these workers must have swallowed a considerable amount of Inhaled dust. Another character istic exhibited by some of these cases was a relatively Jong latent period between the end oi exposure and the appearance of the can cers. In view of these facts, experiment* were undertaken to determine the following: (a) whether chromium would be retained io the lungs or would be distributed to other tissues after introduction into the respiratory tract by inhalation or injection; (b) whether the presence or absence of cancer is related to the concentration of soluble and/or insoluble chromium In the lungs; (r) whether the Jungs have a special affinity for chromium as compared with other body tissues, and (d) what part of the cell is affected by chromium and what reaction chromium compounds have with the cril constituents. The biochemical studies were planned to elucidate these vari ous problems. * i DISTRIBUTION OFiTJIROMIUM IN BOOT TISSUES FOLiAWING EXPOSURE TO CHROMIUM COMPOUNDS The first scries of experiments included analyses of tissues from chromate workers who had died with and without lung cancer and analyses of tissues from animals which * 253 i * BAF.TJER ET AU had been exposed to chromium through in tratracheal, mtrayeritoncat,or intravenous in jection of hcxavalent and trivalent chromium salts. 3. The concentration of chromium in the tumors varied greatly both in different areas of the same rumor and in the different cases but was tower than that m the lung tissue. Human Core/.--Lung tissue and, in some cases, other tissues were obtained at the time of pneumonectomy or autopsy from 10 men who had worked m the chromate chemical manufacturing industry. Of these cases, six had bronchogenic carcinoma, whereas four had no signs of any malignant neoplasms. The tissues were analyzed for both soluble and insoluble chromium.f Lung tissue from 4. In all the chromate cases, the concen tration of soluble chromium per gram of wet or dry tissue or ash was greatest in the lungs. The concentration of soluble chromium in the other organs analysed was variable and relatively low. Add-insoluble chromium was not found in any organs except the lungs, tracheobronchial lymph nodes, and nasal cartilage. two persons with no known exposure to chro Animal Experiments*--In, order to study mium also was analyzed. the fate and distribution of chromium com Although the data from these human cases are meager and variable, certain general con clusions appear to be valid. 1. The presence or absence of cancer did not appear to be related to the average con centration of the acid-soluble or acid-insolu ble chromium found in the lungs at the time the cancer became evident This conclusion was based on a comparison of the cancer cases with the noncancer eases and a com parison of the portions of the lungs where the cancers were located with the noncancerous areas in the individual cases. How ever, the concentration in different areas of the lungs varied greatly, and the concentra tion in the area at the time of onset of the cancer was not known. The concentration of pounds introduced into the lungs, a number of guinea pigs were injected mtratracheally with solutions of sodium chromate or potas sium dichromate. One or two animals were killed immediately after injection and there after at intervals up to 140 days. The urine, blood, and soft tissues were analyzed for chromium. During the first few hours following the injection of the soluble hexavalent chromates, some of the ebromiurn passed rapidly from the Jungs into the red bJood cells and into the urine. After this initial period, the rate of elimination of chromium from the lungs de creased, and the excretion in the urine ceased. A considerable amount of chromium re mained in the lung tissue for some weeks. chromium in the bronchi was lower than that The total amount of chromium in the blood in the Jungs. cells decreased rapidly in the period between 2. The average concentration of acid-solu ble chromium in the lungs varied approxi mately with the duration md extern of exposure. On the other hand, the concentration of the arid-insoluble chromium did not show any very definite relation to either of these factors. The mosl significant finding was the 30 and 60 days alter injection as die blood cells were destroyed. Although the total amount Lrt the spleen was n&U, the concen tration per unit weight increased rapidly dur ing the first 30 days after injection and re mained high for some weeks, undoubtedly owing to the destruction of the red cells. presence of considerable water- or arid-solu ble chromium in the lungs many years after the end of exposure. In the analyses completed up to the present time, no measurable amount of chromium has been found in the bones. fThe micromethod used for the analysis of chromium in these experiments was a modification of the diphenyl cartazlde metl>cd developed in (his laboratory by Sudan. Experiments are now in progress to study the retention in the lungs and distribution to other tissues of trivalent chromic chloride when injected mtratracheally. 2M REACTION OF CHROMIUM COMPOUNDS WITH BODY TISSUES AFFINITY OF LUNC TISSUE FOE CHROMIUM In order to determine whether lung tissue has a special affinity for chromium, sodium chromate and chromic chloride were injected intravenously and intreperitoneafly into guinea pigs. The animals were killed 24 and 72 hours after injection, and the tissues ana lyzed for chromium.The lungs did not remove more than a very small fraction of the total amount of chromium which reached this organ through the blood, and the concentra tion of chromium in the lungs was no higher than that in the liver or spleen. The amount of chromium taken up fay the lung tissue from the blood was approximately the same as that which remained fixed in the lungs four months after intratracheal injection of solu ble chromates. Since bronchogenic carcinoma has occurred in man in response to chromium chemicals hut has not faeeu produced in animals, it seemed likely that the lung and bronchial tissue of man might have a greater affinity for chromium than that of other species. This possibility was investigated by suspending fresh slices of human, rat, and guinea pig lungs in dilute solutions of NaaCr04, KsCr2Oi, and CrCl*. Liver slices were simi larly treated. Preliminary results Indicate little quantitative difference in the behavior of lung tissue as compared with liver or in the behavior of lung tissue from different species toward CrCU. Human lung tissue seems, however, to bind hexavalent chromium to a less extent than does the lung tissue of gumea pigs and rats. Further experiments will be necessary to see whether this differ ence Is significant. These experiments indicate that the lungs do not contain any component which binds chromium to a greater extern than other tis sues and that lung tissue of man does not bind trivalent cationic chromium differently from the manner in which lung tissue of the animals tested binds such chromium. There may, however, be a real difference in the manner in which the lung tissues of the vari ous species react with hexavalent anionic chromium. BEACnOW OF CHROMIUM WITH FROTEIHS ANO NUCLEIC ACIDS Combination of Chromium with Nuclei* Acids.--A study of the ehemiaf reaction of hexavalent and trivalent chromium com pounds with pure deoxyribonucleic acid and ribonucleic acid was made. At a pH of 7, an immediate precipitate was formed when CrCU was added to either of the nucleic add solutions, but no reaction was observable with the hexavafcnf chromates at this pH, and no precipitate formed until the pH was lowered to the point where the nucleic adds themselves predpitate. Analysis of the re action product of CrCU with the nucleic adds indicated that two moles of chromium com bined with one mole of add. Reaction of Chromium Chemicals tw'/fr Proteins.--reaction of the hexavalent chromium salts, sodium chromate and potas sium diebromaie, and the trivalcni sak, chromic chloride, with bovine plasma albumin has been studied. Aqueous solutions of this albumin have their isoionic point at pH 5.4. When these hexavalent chromates were added to protein solutions at a pH above 5.4, the solutions remained dear even after the chromate was removed by dialysis, showing that the protein was not denatured by contact with hexavalent chromates at a pH above 5.4. However, the hexavalent chromates were partially reduced to the trivalent state by contact with the protein, aa some trivalent chromium was found in the dialysate. On the other hand, when hexavalent chromates were added to the albumin and the pH adjusted to a value below pH 5,4, a heavy white precipitate was formed. When the chromium was removed as completely as pos sible by prolonged dialysis, the residual pre cipitate contained approximately 1 mole of chromium per mole of albumin, was stable over a wide pH range, and was presumably denatured. When trivaknt CrCU was added to the albumin solution at a pH greater than 5.4, a precipitate was formed containing protein as well as chromic hydroxide. At a pH below 5.4, the solution.* remained clear, but when 255 BASTJBR ET AL. the chromium was removed by dialysis, a precipitate was formed, indicating deoaturatioa of theproton. This precaphaie contained 16 to 18 moles of chromium per mole of albumins Although such a reaction would not occur at the normal pH of the body, it might occur under some local conditions of reduced pH, sue* as in inflammatory areas. Dr, Baeljer is indebted to members of the De partment of Pathology erf the Johns Hopkins Hosfatal, to Dr. Russe!) S. FSsber, Chid Medical Examiner of Maryland, and to others for providing the tissues included in this study. REFERENCES 1, Machie, W,, and Gregorius, F.: Cancer of the Respiratory System h the United States Chromate- Producing Industry, Pub. Health Rep. 6$:UR mi 2. Bafttjer, A, M.; Putavowy Oaexnoe* in Chtornate Workers: 1. Review of the literature and Report of Cases, Arch, Indust. Hyg. & Occup. Med. 2:4*7, 19S0. 3. Baetjer, A. M.*. Pulmonary Cswom w> Chromate Workers: II. Incidence on Basis of Hospital Records, Arch. Indust. Hyg, & Occup. Med. 2:#5,1950. 4. Gaiaiw, W. U,: Health <d Wwkess Chromate-Producing Industry, Publication 192, Federal Security Agency, U, S< Public Ilealth Service, 1952 5. Mancuio, T. F., and Hueper, W. C. > Occupa tional Cancer and Other Health Hazards in a Chromate Plant: A Medical Appraisal: I. Lung Cancers in Chromate Workers. Ifldust. Med. 2: 35S, 19SJ. 256 A Bioc&enkttl Costf&atkn The results of these experiments arc given LfSm P. SCNEEL, Pfeb., Seraue Lake N. Y. to Figure \. These results show that the rate of solution of the glass particles is decreased by the addition of the sodium silicate, even though the solution is alkaline and the rate The detnonstration by Gye and Purdy* of solubility of the glass is greater than the m 1922 that colloidal silica was toxic led to rate of solubility of quart*. the theory that the fine particles of silica dust dissolve in tissue fluids and cause precipita tion of a toxic colloidal silica. The first reac tion which must occur at the surlact of qvsana particles to bring about such a result would be one of hydration. The "soluble silica" theory may be a pos sible one if io the living tissue the silkic add were to combine with some constituent and accumulate until gel formation took place. To test this idea, protein solutions contained to a dialysis bag were exposed to silica solu StOs-f-HiO^HjSiO# tions and samples of the silica solution were Scbeel* Fleischer, Klemperer, Smith, and Van Riper f found that if quart* particles !* to 3/t in size are exposed to distilled water for 15 days continuously, 0.18 mg. of silica is dissolved. If, however, the solvent is changed each day, 032 mg. of silica is dis solved In 15 days. If instead of distilled water a salt or a protein solution is used as the solvent, the amount of silica dissolved is much larger. To teat the possibility that the analyzed at intervals until no further change in silica concentration took place. In these experiments it was found that there was no demonstrable interaction of protein molecules with monomolecular silicic acid. However, it could be demonstrated that if colloidal silicic acid formed in the protein solution protein precipitation took place after about two days. It fiten became necessary to determine the sotobU&y of geV rate of solution of silica may be inversely proportional to the silicic acid concentration in the solvent, the following experiment was performed. Pyrex glass was fractured in a mortar *nd sieved to remove the oe and coarse particles. The frag* marts, about 1 m in diameter, were placed in a gkas ftc and washed alternately with 2% sodium carbonate solution and J% hydrochloric acid tstiil the amoont of glass dissolved by expo sure for five minutes to the 2fe sodium carbonate solution bee&nte constant. Small amounts of sodium silicate were dies added to the 2% sodium carbon ate solution, and the amount of sflka dissolved sn five minutes was determined. To do this, dry silica gel was suspended in water, apd the solvent analysed at intervals ior silks content by the molybdate WuC method. In another bottle a solution of sodium silicate which }i*d beet) titrated, to pH 7 was allowed to gel and to equilibrium. The colloidal siikxc add was removed by filtration through a diai/sis membrane in a centrifuge and the filtrate analysed The results of this study are presented in Figure 2. The equilibrium value of 166 mg. per liter of soluble silicic acid in equilibrium with silica gel exceeds the values reported by King * for the solubility of silica to body fluids. Animal experiments conducted by The ' Recorded for publication June 6, 1955. Saranac Laboratory have failed to reveal4 The Saranac Laboratory. any toxicity due to silica gel or molectdarly '* References 3 and 2. dispersed silicic acid, because the silicic t References 3 and 4. acid is rapidly eliminated from the body 257 t m SO, DJ90U 5B M W CUSS N S MWTSS& FIGURE | SCHEBL fluids by the kidaey. The tcaa&formaxG of silicic acid solution into colloidal silica gel is inhibited by the presence of alkali salts and protein in the solution. It i$ extremely unlikely that solution of particulate silica could produce a concentration of silicic acid sufficient to form colloidal silica at any point within the animal body, It became necessary, therefore, to study the surface reactions of quartz particles to determine the toxic action of this material when trapped in animal tissue. The nature of the pathologic lesion, a nodular growth limited to an area containing particles, suggests that the tissue stimulation is limited to the area containing the particles. In considering the experimental approach to a study of the surface reactions of quartz partkks, definition o( the nature oi the sur face of the quartz is pertinent. The crystal line structure provides a uniform surface pattern in all particles. Further, each oxygen atom is linked to two silicon atoms, and when the crystal is fractured, the new surface cre ated must undergo a readjustment of forces within the surface. This readjustment of forces within the particle surface results io a certain residua! stale which is called surface . 5,0/ l * FIGURE 2 2$fl SURFACE PROPERTIES OF QUARTZ DUST tension or surface free energy. The quart! surface has one component of this surface free energy which can be characterized. This component is the negative charge of the partide in water solutions. This surface charge is a colloidal characteristic which is a static expression of the nature of the distribution of forces in the surface of the particle. How ever, this static charge can exert a field effect on polarizable materials, just as an electrically c^rged condenser can orient a polar ized metal object. sorbed wiU be proportional to the concentra tion of the protein solution.. In 0.01 crys talline egg albumen solution, about 1 mg. of protein is adsorbed per gram of 1? to quartz particles. If the concentration is in creased to S% egg albumen, the amount of protein adsorbed increases to 120 mg. of pro tein per gram of particles. By altering the hydrogen ion concentration of the protein solution, it is possible to give the protein molecule either a negative or a positive charge. Thus one can test the effect . WSTOBTKJf* OF PftOTEIW KOUCOUS fit ADSOBPTIOW Protein molecules are polarizable in an electric field and as such might be affected by the surface charge of the quartz particle. To test this idea, crystalline egg albumen was chosen, because it is a protein obtainable commercially in a reproducible state of purity. Further, egg albumen is a protein which produces in the rabbit specific anti bodies to the native and to the denatured sate. Thus it might be possible to determine the state of the protein on the surface of the particle if adsorption took place. Our previously reported experiment * showed that quartz particles 1* to 3* in diam eter cart tenaciously adsorb protein to their surface and that the amount of protein ad- of the charged silica surface on the adsorp tion of protein molecules bearing various charged states. The alteration of hydrogen ion concentration in the suspending solution will not affect the nature of the silica surface forces. The amount of protein adsorbed may be expected to increase uniformly as the neg ative charge on the protein decreases. When the protein. molecule becomes positively charged, the amount of protein adsorbed in creases sharply. Thus the charge on tlie sur face of the silica particle plays some part in the adsorption of protein molecules to the surface. In an attempt to characterize the nature of the protein adsorbed by the quartz particle, 259 SCHESt rabbits were immunized to native and to de natured egg'albumen. Quart^pamdes were then coated by exposure to native albumen solutions, washed thoroughly, and tested tor agglutination by exposing them to the anti* bodies of immune rabbit serum. It was found by this test that the particles reacted with particles was planed at each injection &e. A similar quantity of wteoated qoaru particles from the same batch originally suspended in saline was injected subcutaneously into the other rabbit ear at the same tone. The site of injection was removed at isttemla (com ibt n&H ear by means ol a sharp cork borer, fixed, sectioned, and examined microKOpfcaJlf. both native and denatured albumen anti bodies. To determine whether the alteration in the protein characteristics during adsorption on The result of this experiment confirmed eytobiologicaliy the presence of tbe adsorbed protein layer.* the surface causes a permanent change in the protein structure, some of t!*e adsorbed egg albumen was eluted aod tested with the im mune rabbit semm. The eluted egg albumen was teund to react only vrith native anti bodies. Thus the structure of tgg albumen ad sorbed to the particle surface has been shown to be altered only during the adsorbed state. Evidence for tiw solubility and surfaceactios theories of the actios of quartz is re viewed- The cate of solubility of glass is greater than that of quart*. There is no demonstrable initraction be tween protein molecules and monomolecukr silicic arid. This effect may be schematically presented as shown ta Figure 3. Thus in the adsorbed state the protein molecule is distorted to such an extent that the surface presented to the immune anti bodies Has lost Its structural specificity-. Silicic add is rapidly eliminated via the kidney, thus preventing its concentration to form colloidal silica. Quartz particles have, because of their sur face characteristics, the faculty of adsorbing and denaturing protein. This description of protein adsorption and The effect of this adsorbed layer of protein alteration is evidence for the formation of a new surface on the inhaled quartz particle which is presented to the body as a result of the protein content of the interstitial tissue fluid. In an effort to determine the effect of the protein coat on the tissue reaction, the following experiment war carried out. Quarts particles Ip to 3* in diaweter were sus pended in a saline solution at a concentration of 1 mg. per milliliter by boiling under a reflux condens er for four horn's. The particles were then coated with rab&t eerem fay adding 2 mi. d serum to 20 ml. of the suspension of quartz particles asd agitat ing the mixture gently lor eight hours. The stmpen sion was centrifuged and the supernatant solution decanted and discarded. The protein-coated particles wtTt washed *>,< times by resuspending them h Id ml. of saline solution and separating them from the wash by centrifugation, The washed particles vet next suspended in saline at a concentration of 10 mg, per milliliter, and this suspension was injected sub cutaneously *mto the rabbit ear so that l mg. o/ on animal tissues was. experimentally inves tigated. REFERENCES 1. Gye, W, E, and Purdy, W. Poisonous Properties of Colloidal Silica: Efiects of Parenteral Administration of Large Doses, Brit. J. Exper Path, 9 57S, 1922. 2. Gye, W. and Purdy, W, }.: Poisonous Properties of Colloidal Silica, Srit. j. Exper. Path. 6:23$, 192< 3. Scheel, L, D.; Fleisher, E, and Klemperer, F. W,: Toxicity of Silica: I, Silica Solutions. A, M. A, Arch. frsdem. Hyg. $:564, 1953. 4. Scbeel, L. D; South, R; Van Riper, }<> and Flrisher, .: Toxicity of Silica: If. Characteristics of Protein Fihns Adsorbed by Quartz, A, M. A. A?ch. IwUnt. Hyg. *., S9S4. 5. King, E. j.: Solubility of Silica, 1:1236,19i$. 6. Schepers, G. W. H.r CytobJoJogical Manifestafsosis of the Surface Plenties of Qojrrir, A. M. A. Arch, indust Health 12:266-275, 1?SS. 260 * SCHZPSfiS Fig. Reseticrt to quartz introduced Mdxtfeaacously tats rabbit ears j*wtr). A, *,RGotte4 qwrta*. seven hour;; initial hx\ii of reactlce. B, pfatdn-eoattd quartz: swen tetitv, ;oifel iactwn snbies Field A. C, tincoaced quart*: nine days; iimd, circumscribe teroi* necrotic rcsidouen, D, orotcio-eoaAtd <^m: nine toys; expanded, proliferative, fibtpcellutar ^raaafcraa. While these major lesions are inttsesdng 10 contemplate, ?fce essential dances are more readily observed under high-power and olMmmersiof: microscopy. Typical features at the quanta mass center, at the edges, and in the ftunofcudmg tissue? have been assembled in Figures 2 to 4. dal zone the eo&fuopbifes and histiocytes and occasional plasma tells, lymphocytes, and 6'orocytcs are migrating toward the primary lesion. There Is a little hyperemia subjacent to the dust focus, but this is not a significant feature, and there is no extravasation ol erythrocytes. SERIAL TISSUE BSACTtOfcS Okos'(*--Seven Bows.--The basic reac tion is iveil defined within seven hours. At this stage the essential process consists of marked aggregation, around the mass ol par ticles of eosinophilic polymorphonuclear leu cocytes and histiocytes with a small propor tion of plasma cells and lymphocyte* (Fig, PA), Interstitial edema, may be seen for a distance of abo\ji 2 mm. ah around the quartz deposit, and in and beyond this circumferen ce* Where the dust is well contained as a cir cumscribed focus, a decisive wall of deifur cation separates it from the circumjacent edematous tissue (Fig. 'SA), This containing wall is composed of amorphous matter (al tered tissue protein) in which come fibrocytes and collages may be seen, The cells appear to be relatively Healthy in this zone. More centrally, necrosis has commenced and mani fests itssif essentially as disintegration of *ome ol the eosinophiles, whole granules and nuclei being scattered among the quarts par- t Fig. 2<--CytocIa4tk processes it the carter of the quartz mass (oil immersion). A, uocoated quartz: seven hews; commencing cril damage; dominant ceils are eoain^phBes with a few lymphocytes. B, prottie-costed quarts: seven hoars; no lymphocytes present, C, uncoUed quartz: 12 hoars; extensive protein precipitaticfli demonstrated D, protein^oated quarts: 12 hoars; ceils are better preserved and tissue protein denaturing less advanced. E, oncoafed quartz lesion: 24 hours; celf approximation and darrege. F, proton-coated Quartz: 24 hours; greater survival of cells and nuclei. C, wicosted quartz: 72 hours; marked necrosis. H, protein* coated Quartzi 72 boors; some karyottbexis presotc tides. The lymphocytes, plasma cells, ami histiocytes are more resistant to injury by the quartz (Fig, 2A). Protein-Coaled Quarts--Seven Hours,-- At the corresponding seven-hour stage, the tissue reaction provoked l>y the introduction of 1 mg- of rabbit scrum-coated particles of quartz ibows many similarities to the reac tion to uncoated quart* but also differs from it in several significant respects. In both instances there is a marked aggregation of cells in relation to the mass of foreign par- tides, and a surrounding hak> of edema is present in which cytotropic effects are to be seen. - Though the' protein-coated dust deposit remains limited to the site of injection, no decisive line of demarcation kt respect of cyfologicat response is noted- The new cells cwcrSow the edge of the panicle mass and shade of! gradually into the surrounding tis sue. No degenerated formed elements are to be observed (Fig, 3#}, ` 263 4 m ivr*i* N.>: ..* *.* / / iSf rv- lC..f .*.* CtfFA5 Fig, 3.--CeiWar phenomena at the edge of the site <rf quart* detrition {fields A--Ds high power; F&ds --??, oil immersion). A, uncoated qoarlz: seven hours: sharp dfnarcMiou oi reactive zone. i?, protein-coated quartz: seven hoars; absence of sharp edge delimiting the reac tion to the quartz mass. C, uncoated Quartz: 12 hours; commencing htsekeytic invasion of borders; D, protdn-eoated quartz; 12 hours; zone of transition obscured by migrating Quartz* fitted tstts, E, ssiteamed Quartz: 24 hours; ffcrocytaa and histiocytes advancing on quartz mass, F, protein-coated quartz: 24 hours; eosinophils, lymphocytes, and histiocytes, G, uncoated quart*: 72 hours; ftbrocytes aggregating together to form a continuous capsule H, proteincoated quartz: 72 hours; particle-filled histiocytes with intervening fibrccytes. Once more there is an accumulation of coated quartz particles. Occasional fibrocytes eosinophilic polymorphonuclear leucocytes may also be seen, and histiocytes among the proteio-coated quartz particles (Fig. 2B). This time there are, however, no plasma cells or lympho cytes ; norArc the fetter ceti types to he seen in the surrounding tissues. Though eosinophiles also predominate at the center of tlxr Though there is some suggestion of necro sis within the denser areas of cells, this cliange has by no means attained the stage seen m the sites of uncosteri quartz. Once more this necrosis is limited to the eosino phil* polymorphonuelears. The histiocytes, on the contrary, show ingestion of the pro lesion, there is now a higher proportion of tein-coated particles to a marked degree with histiocytes migrating toward the mass of out any apparent injury. l` 264 CYTOBIOLOGICAL MANIFESTATIONS OF QUARTZ \ Fig, 4.--Sequence oi eytologicaJ changes in the peripheral zone around the quartz site (oil immersion). A, wicoated fluam: 12 hours; phalanxes of eorinophUf* advancing on the lesion, B, protein*eoa(ed quartz : 12 hours; sparse presence of histiocytes, C, tmcoated quartz: 24 hours; fibrocytes abundantly present. D, protein-coated quartz: 24 hours; histiocytes, lymphocytes, and eosioophiies. E, uncoated quartz r 48 hours ; admixture of fibrocytes and histiocytes, P, protein- coaled quarts: 48 hours; pirtidc-fied histiocytes, departing (ran the quartz ate, passing fibrocytes and histiocytes advancing toward it G, tuicoatcd quartz: 144 hours; subsiding cyto- lopcal response. H, protein-coated quaitt: 144 hau.lv, fibrocytes interposed among emigrating particle-fdkd histiocytes and immigrant histiocytes. * Quariz~~T%uehe Hours.---After 12 hours, the reaction to the tmcoaied quartz has ad vanced, The particle mass still retains its circumscribed character, but the whole is now cut up into multiple units by interposed cellu lar elements, the lesion giving a reticulated sectional effect. There remains & sharp line of demarcation between the focus of reaction and the surrounding edematous zone (Fig, fC). However, this edge is no longer formed by a peripheral condensation of cells or formed elements, as the whole of the center now has opaque amorphous protein frag ments evenly disposed throughout it (Fig. 2C). i M the periphery of the lesion aod farther afield the cytological response now is an al most pure1 eosinophile outpouring. Solid phalanxes pf these cells may be found ad vancing on the quartz mass, and more such i 76$ SCHSPERS . Iq (he surrounding tissues there are but few cells, and these are predominantly histio cytes, though some eosinophifes are yet being attracted. No plasma ceils or lymphocytes are m evidence and but lew frbrocytes (Fig', 45). Quarts--~Tzventy-jour Hours.---At the end of the first day (24 hours), the edema sur rounding tlie quartz reaction has receded to some extent. This emphasises the sharp litve of transition between the necrotic cellular zone which is coextensive with the mass of quam particles. The majority of cells within the lesion are now necrotic (Fig. 22). The injury they sustain is limited, however, to the cellular cytoplasm, and nuclei show pyknoste and karyorrhexis to a limited extent only. Much of the fluid within the lesion has been with drawn, so that the cells are densely crowded together. At the edge of the lesion fibrocytcs are accumulating (Fig. 35), At the petipljcry of the lesion great num bers of large fibrocytes and even fibroblasts may be found among the eotioopbiles and histiocytes. Such fibrocytes are present even at a considerable distance from the dust mass (Fig. 4C> Protein-Coated Quarts -- Twenty']our Hours.--The lack of definition of the edges 266 of the protein<oated quartz lesion Is further emphasised at the 24-hour stage (Fig. 3f)< It is quite evident that this dust is being dispersed beyond the confines of the initial site of deposition. At considerable distances from the lesion, therefore, histiocytes may be found which have phagocytosed the particles and art transporting them away from the original site. More histiocytes art to be sttn advancing on the dust site (Fig. 45). The accumulation of these cells may account in some measure perhaps for the preponderance of histiocytes over eosinophifes, but it seems certain also that the number of the latter type of cells has fallen off somewhat, In the center of the primary site there Is some additional evidence of necrosis (Fig. 2F), but it is apparent that the cells and formed elements remain well protected against the nocuous effects of the quartz as a result of the inter posed ptotein layer. Qwat*~-Forty-eipht Hours.--By the end of the,second day there are few cells surviv ing intact in the center of the injected area. At the edge of the lesion rafber more are seen which have not undergone too great a change. At the periphery of the lesion fibrocytcs are now dearly the dominant cell type (Fig. 4B). They may be seen advancing on the quartz zone in large numbers. Occasional histiocytes and eosinophifes lie among them. Many of the fibrocytcs have taken position around the quartz arcs, and others have pene trated ijrtu it. The edge of the lesion has become somewhat irregular through the emergence of dust-filled histiocytes from the central area. Protein-Coated Quartz -- Fvny-tiphi Hours.---In the case of the protein-coated quartz, on the contrary, the periphery of the lesion shows bo! few fibrocytcs, and*the dom inant cell still remains the histiocyte. A larger proportion of these cells are now filled with particles and, judging by the constant posi tion of the nucleus tn station to the particlefilled cytoplasm, may be presumed to be departing from the quartz area while the distended cells advance on it (Fig. 4F). The CrrOBtOLOGJCAL MANIFESTATIONS OF QUARTZ edge of the lesion is cow a little better de fined, owing to the accumulation of a zone of nuclear debris around the necrotic center. cytes progressively come to lie between these macrophages so,that ultimately the interme diate capsular zone consists o a mixture of Cell destruction has advanced further during the past 24 hours and has reached the stage the uncoated quartz had already brought about a whole day earlier. distended histiocytes and fibrocytes. This zone increases progressively, and by the 10th day it equals in width the residual central! necrotic core. Capillaries have now Qaarls--Seventy-two Hours.--The most also penetrated into it, and along extensive distinctive feature marking this stage of evo stretches this zone is sharply demarcated lution of the quartz lesion is die incipient from the center by layers of fibrocytes. The emergence of a capsule (Fig. 2G). This com necrotic area cow consists largely of an ponent tends to consist of two elements, acidophilic granular celt debris within which namely, a circumferential multilayered zone nuclei may persist. Quite a considerable and an internal layer, intermediate between amount of quartz is still retained within it. Use fibrous capsule and the central necrotic urea consisting mainly of greatly swollen, dust-filled histiocytes. A large: number of fibrocytes have also >esietrated Into the edge of the necrotic mass, and it is plain to see that the essential process h now that histiocytes carry the dust to the The superficial fibrous capsule has not de veloped any further. The whole terminal lesion is now relatively well circumscribed and about equal in size to the original area of reaction. At the periphery the cellular reaction has become relatively quiescent (Fig. 4). outer edge, while fibrocytes insinuate them* selves refo the necrotic area. A small locus of ccttular debris remains in the center (Fig. 2<?>. Protein-Coated Quarts -- Seventy-two ^Vbilc there is now a comparable tuiKtency toward peripheral fibrocytic aggre gation, a decisive capsule is not yet being formed, probably owing to the greater dis persal of ihe dust-laden histkxytes into the surrounding tissues. Indeed, it would seem that at this stage almost more protein-coated quartz fMtilscles are confined within greatly distended 'histiocytes outside the original focus of injection {Fig, ZH). The central portion of *h<i lesion appears consequently denser because of closer approximation oi the cellular cotnponents to one another through withdrawal of the particles (Fig. 2H). Protein-Coated Quarts--Fourth to Tenth Doy<-~0wing to the initial greater range of peripheral dispersion of the quartz particles through the centrifugal migratory propensi ties of the histiocytes and the diminished cytotoxic effect and the delay in fibrous reaction at the edges, the cross sectional area of the ultimate lesion provoked by the pro tein-coated quartz particles is almost four times as. extensive as that due to the un coated quartz, and the residual necrotic center is all but resorbed, sis edges merging with the surrounding cellular zone with no tendency toward the deposition of interven ing fibrous layers. Nor is the outer zone too clearly defined from the surrounding tis sues, a decisive fibrous capsule never having been laid down. The edge of the whole lesion is now rather better demonstrable, however, by virtue* of the marked contrast between its Quarts---Fourth to Tenth Day.--The final intrinsic jhighly cellular character and the pjoccss of coping with this mass of foreign relative, acellularity of the surrounding tis particles appears to consist of a progressive sue from, which the intense eosinophilic and increase in the number of dust-filled histio histiocytic reaction, previously so much jn cytes in the zone between the peripheral eridencejhas been conspicuously withdrawn. capsule 2Jid flie central necrotic area. These The mam mass of the granuloma now con cells appear unusually well preserved despite sists largely of particle-filled histiocytes and the presence of particles within them. Fibro fibrocytes (Fig, 4#). Owing perhaps to the SCtiEPERS 5act that the histiocytes had traveled farther aad'become better spaced apart, relatively greater cumbers of Bbrocytes and other ceils intervene among the individual histiocytes. Capillaries are also more numerous. Occa sionally eosinophiles are yet present- A fairly considerable amount of fine collagen has been deposited between the histiocytes, especially at the edges. The residual central debris is now much more of an amorphous basophilic mass than U the case with the pore quartz lesion, tn Both forms of quart* immediately attract to then) a Urge and equal number of histio cytes sad eosinophilic polymorphonuclear leucocytes, the latter initially being destroyed almost as rapidly as they reach the quartz masses. Very soon, however, it becomes evident that the pure quart* particles are the more destructive, and the initial necrosis, therefore, proceeds the more rapidly in rela tion to them. The protein coating of the quart* in the relevant lesions, on the con- Fig, S.--Differential connective tissue cellular reaction to uncoated asd protein-coated quartz particte, showing manner of evolution of eccapsulated and proliferative lesions. which nuclear structures are still distinguish able, the cytoplasmic remnants of the cor responding destroyed eells imparting an aci dophilic character to the area. Virtually no quant particles survive here. COMMENT The differential effects of uncoated and senun-coated quant in the rabbit ear sub cutaneous tissue art apparently explicable m terms of the relative rales at which cytolog ies! events follow one another and have been schematically summarized in Figures 5 and 6. 26$ trary, affords an initial protection to the leucocytes. As a result ol the marked local toxicity of the pure quartz, a peripheral protein barrier is set up which defines the lesion from sur rounding tissue. The protein-coated quarts docs not provoke this interstitial reaction. Instead, the line of demarcation Is soon lost. The latter change is accelerated by the behavior of the histkicytcs. In the Case of the protein-coated quartz, these histiocytes are not immediately as seriously injured as are those which phagocytosc the pure quartz cyzomoiociCAi manifestations or quartz particles. Consequently the histiocytes mi grate beyond the confines of the protdncoated quartz deposit, whereas this change it aot seta to any great extent to the case of the quam deposit. this manner the protein-coated quartz is immediately more widely dispersed. At the same time greater numbers of histiocytes advance out of the zone of the protein-coated quartz deposit and take the place of those which have es caped outward tutty charged with their par ticle loads. The uncoated quartz attracts fibrocytes more readily to thetr vicinity, and thus a fibrous capsule is more readily thrown up which further limits the spread of the lesion, the whole subsequent process must now pro ceed within the confines of this capsule, which tends to limit or retard the entry of histiocytes and to determine the strong ional differentiation which ultimately ensues. In the case of the protein-coated quartz lesion, virtually ail the quartz is rapidly withdrawn from the original site by the phagocytic histiocytes. This feature deter mines the final absence of a line of demarca tion between the cortical fibrocellular zone and the residual central amorphous center. The generous subsequent deposition of fibrous tissue between the histiocytes may perhaps be explicable on the supposition that a fibiogenic stimulus is gradually released from the quartz particles contained within the histiocytes. The final conclusion which may be arrived at is that these different effects are entirely explicable in terms of some barrier action which the protein coating, which is adsorbed onto the particle surface, exerts. This barrier for connective tissue ceils which the quartz may thus modify the selective chemotropism panicles exert. The uncoated quartz immedi ately attracts eosmopbiJes, histiocytes, and fibrocytes. The coated quartz has a stronger tropism for histiocytes, lire delayed attraction of fibrocytes by the protein-coated quartz after ingestion by histiocytes may perhaps be explicable on the supposition that the protein layer is slowly digested off the quartz and tnttabolized, whereafter a histiocyte filled with such p&Ttides would not differ materially from one initially filled with uncoated quartz. At this stage the quartz would commence to exert 269 SCHBPERS its full deleterious influence oa the living cell components, ' The greater migratory property of the protein-coated-ffuartz-filled histiocytes may perhaps also be explained on the assumption that such cells are protected for a short while from injury by the quartz, which mani fests ftself only after the protein layer has been digested of?. The whole phenomenon affords good con firmation that protein is indeed adsorbed onto the quartz particles and sound evidence that such particles exert their harmful influence on tissue cells by virtue of the physico chemical phenomena which operate at the quartz particle surface. suatUASY Serial cytobgical responses to the subcutaiKiWs introduction tA protein-coated and uncoatcri ty to Sy quarts particles arc described. The adsorbed protein acts as a barrier which selectively retardsand modifies chemo* tropic and cytociastic responses to the pres ence of quartz. The quartz, is consequently more widely dispersed by histiocytes, with a resultant exuberant fibrocellular lesion. REFERENCE 1. Scbeet, L. D,: Study of the Surface Proper ties of Qitfru Dust, A. U. A. Arch. Jndust. Heahh 12:262.265, >9SS. ^4n xperimentai.Study. tlie dd^J^ectd 4QUW,,oi on nimai <jCuny4 G. W. K SCHCMItf. M-0,, 0.3c and ANTHONY B. DZLAHAHT, Ur**ac Ufc, H, Y. The increasing modern industrial applies* tion of glass fibers in the production of rein forced polyester resin plastics has revived interest in a series of experiments on glass wool and glass cotton in which one of us (A. B. D.) participated during the period 1939-1947s These studies were conducted In The Saranac Laboratory under the direc tion of die late L. U. Gardner, M.D,, whose unexpected and lamented demise prevented the publication of reports on the results obtained. Three samples of glass wool were studied ty the intratracheal Injection technique. The experimental animals were guinea pigs. In addition, a long-term inhalation experiment was conducted, using glass woo! during the first phase and glass cotton toward the end. This study involved the use of guinea pigs and rats. INTRATRACHEAL STUD* The diameters differed in the three glasswool samples. The first batch (Batch A) ranged from 3#* to in diameter, with an average diameter of 6f*. The second batch (Batch B) was approximately S/i in thick ness, and the third hatch (Batch C) meas ured 3/* and less in diameter, a large propor tion being in the 1#* range. The desired length of the fibers for the intratracheal studies was Recorded for puWlealion July 11, 1955, Director (Dr, Schepers) and Research Associate (Mr. DetahanO. The Saranac Laboratory. Photomicrographs of three batches of glass wool after reduetke for purposes of intratracheal injection. A, reduced about % from mag. X 100; B, reduced about Vi from snag. * 300; C, reduced about Vs from mag, X 300. 20p-50p. The fibers were prepared by pre liminary grinding in & carding mill and were passed through a 200 trresb screen, ground Kghiiy in an agate mortar, and separated by sedimentation in water. Two of the prod ucts were then prepared as 5% suspensions and the third as a 0,5% suspension by weight in isotonic saline. All three were thereafter arooldiaed at 100 C for one hour. The Figure illustrates the physical appearance of the glass fibers from the three batches. The glass fibers were introduced imratradwaJly in three doses of 03 cc each at weekly intervals in each case. For Batch A, five guinea pigs were used, and all survived the process for a year. For Batches "B and C, there were eight animals each. Two deaths oeeurred in each group, and there were, therefore, enough animals in each group to permit 271 i SCHBPBRS AND DELAHANT Tabls lr-Pvb*>*ary Bffecltof Glass-Wtel Fibers Intratracheal .Experiment 905 ~+ CtftM Oflift** Su> DM wool, Tn run, Nw. Vgp '*- $r* Fb1sob>7 Be**se Otb*rtowewo*bfr*t lrttdebU*Jtoff*l Lm iwnmk toes tostotoJeo trta So* i4tt tniti fefe* it* faruue Peeusof etelaeUeU NMUl M3 nseaiMl* irltb otcretfe an*s 6um*I nd lABaTawtMeuwwDfOtaeantM 4?HU BooU MtfsulMt* *# WaetoM gigamttsa **r HfoertMn Utons 9t M> PtwffntfotBclMe ,t*a*hw -- ufr ' PbwBbqbIs *wd Brill* ' fectl ticketMi * Oae toen 1 iWnMi , An* t aftfswfs la #** mtoSSaacf samplings at 4-, 8-, 17-, S3'-, aod 52*wtek interval*. Ic the cue of Patch B, animal* were 76 and K weeks after the mlliai injecticn. insai-atiok srunv The fibers of the glass wool used in the inhalation study approximated 6p is diam eter, The materia! was dispersed from a modified dutt hopper in a dust room measur ing 8 by 8 by 8 ft, The dust concentra tions inside the cages ranged from 0.143 to 0.146 mg. per cubic foot, as determined by the electrostatic precipitator method, Impinger counts gave reading* ranging from 1,400,000 to 2,200,000 particles per cubic foot of air by light-field count These were die maximum concentrations obtainable by this method of dissemination. Chemical analysis oi the parent mateml yielded the following percentage composition: Co0>|MB<9t BIO............................ ............................. JttO*................. AbO, ......... ............ B ...................... .............................. 0*0 ............... . jfcO ..."........... KQ.................. .. HtiO ...................... SWJ ................... .. H0 ........................ % t# UA bsziired gwwea pigs were exposed to fix ' The results of these intratracheal studied love been summarized in Table 1. It would appear tiuie glass wool of the first type, A, was relatively inert. No animals died, and the gi& wool for a period of 40 months. However, at aboot the 20th month, the nature of the dsrtlog agent was changed from glass wool to glass cotton, with a naxijoum fiber diameter of and a esnccBtratn of 0.03 to 0.07 mg. per cubic foot of air pulmonafy Stsiswn were rrmnmaS: This resist may have been anticipated iri view of the relative thickness erf. component glass fibers. - In the case of glass wool type there were no early reactions except for fbd of atekcUsis. However, in the animals lolled j^fter the ,75th week, major pulmonary dam age- was revealed,' - vij\. ; Glass wool of the third type, C, whose component fibers were relatively slender, was maintained. The experiment was ther^fter coodnoed until the end of the 40th month. A series of 50 white rats were likewise exposed to glass wool m the same chamber far 20 months and subsequently to glass cotton dust until the end of the'24th month. . Animals were killed in batches of three to six at 2-, 4-, 9-, 12-, 38-, 24-, 36-. sad 40mon(h intervals. The observations are re corded in Tables 2 to 5. appeared to provblce mainly focal atelectasis. ; The prevalence of focal atelectasis is ex ceptional- i this series anti may represent a specific type of reaction to the introduced glass wool fibers of the caliber and length used in these studies. It is to be noted that no fibrosis was macroscopieafly perceptible in relation to these areas. OBSERVATIONS Attention may first be directed to the differential mortality rates for the guinea pigs and rats, respectively. Seventeen out of one hundred guinea pigs and twenty out ! fifty rats died during these experiments. It should be recalled too that the guisea pig experiment was carried along for 40 months. 272 EFFECTS OF GLASS WOOL ON ANIMAL LUNGS Table 2.--Effect of Inhaled Gloss Wool end Gloss Cotton on Guinea Pig Lungs Spontaneous Deaths Table A,--Effect of Inhaled Glass Wool and Gists Cotton on Rot Langs Spontaneous Deaths tom** pHmi. Son WT Cauar of Death Duet BeaeUea as K ,o 1 61 ss ee f at : Nfi 10 tfB Bowel c- > Isolated fod of brows i/n tOvk nltnaflUdos O m Pneumonia Bwaaonoc up lot m SsterlUa twm tT its Geometric patten ot pJnwotatioa anteri orly, wf(A isolated; foci ekewton tS us : ;, uc . * i r?v m , S ;imu * FbeumoaJe % CooseaOos.wItt Jteeer sad load plrnest*UOB Dark trees tart* dl* cma fod ot pimee< Utlte aawrlorty- wKB rroaHfr tod postedorly OOeeured by paeetBoota preceee Dark grcea foelot alg< meauttoa urtertofij . ^vHfctlie rat exposures terminated after 24 tnonths? Only nine guinea pigs had dlfed by pie did pi the 24th month. The ratio bet^reert gtrinea pig and rat deaths under identi cal environmental stresses, therefore, comes to 9:40. U In all but. a few instances deaths were attributed to-pneumonia in the case of the guinea'pigs, while the rats likewise died of pulmonary inflammatory states in the major- 8 f oases' In tig case of the guinea pigs, $>3eathai/are irregularly dispersed over the tyhple 40-month period, and ,there is no ` '' >* $"abe'3.--isffect of Inhaled Gloss Witel and Glass -C^ton on Guinea Pig Lungs Serially Killed Animals'- , ' yvrv!"W!!!!!!!aaa!;:M maag ` A. / BDIaC' - '' Gofeea/bPwfcMtt. ftfj, No. Wk. Grose Fetoceart DuAftcecttoe :*.* }. "'I -wi/ ,1,1 *. . fA kUr*ln! auketatfc im S*n^-. a s*> n laoUted subpleorsl fod of blade plgneot, wiia pleural mrmetioo }im J'oti of'gtetetssli: eoettartd to eoafl;teot plg7Bi*UoB, vita SM Incipient geometric pattern }*?t toi5 I \ Ud 40toM.W.flO] Snell discrete fod of dark two pigwatBUoa aaterforiy out TS-ftl Si,84J m MM--............. Dsrk: men ptfUKBtatfeB. wlta sriy 8m*tric patient orlj sad wMeir scattered tw isted fod elsewhere ButBata. **, 80. wt n 10 It 0 IS <8 K2 41.41 tl. U a so AS U S K u at R 44 as O >0 * sa rr as as 46 m/ *?' m B ' 104 eCtDaevawUi PBcataocda t PMuaoaft Sttcabeeeaa Qroee Feh&Q&*n DuitBeeetloB na Uttotc fod ot ptc< HamtaOoB Pieora'. ptgmBto3 pleouei < LBBsebeceee Abdominaltugor 2U OoUapeenluog tadcoatralaieral OBybyeema Tmf abeew Scattered aoduSto Lieu ebiifwr - SSe sUod Arone f . NO Pfrueaud loci aoG pEwraJ plague* FXMBBO&ia t .t Nil focue ot pigEBCDt pieoral piciaeoted pUgwa mortality pattern which could not be ac counted for readily by normal chance and the influence of age. The majority of the rats, on the contrary, appeared to die after the first year of exposure, and there is a maximal or peak death rate between the 50th and ?0th weeks of survival. ; It should also be observed (Tables 4 and 5) that lung abscesses were relatively com mon In tire rats (109&). On macroscopic inspection, these abscesses resembled tumors. Comparable lung lesions were not found to the guinea pigs. In this group of animals there we signs of regional alimentary tract obstruction with distended stomach or large bowel in 7% of-the pigs. This lesion, on |Tasle 5.--Effects of Inhaled Glass Wool and Glass Cotton on Rat Lungs Serially Killed animats muot RlU, HaWreak, MO. . Wk, Grose FuBoonary DustBeacffoo 1,1 a, 4,s .f,s n 17-tD.SO fc 4?A9 16 S9 B 7 % in } lMllad 10 xoodcretc number* ot BtlaaM pigmented foci Spare* Neck fod tea ties 1 mm, } vltb afekeutk art** Panao&k em Id Rat IS Soane focal plgareatattoa Bat es-rtrostc upper tote tumorSka abMeas present 273 SCHBPERS AXD DELAHANT further analysis, appears, however, to have affected animals during the 30th month oi tBesr survival and probably has toothing to do wfh the glass wool, probably being due to a dietetic factor or imercUTTem infection. Id the guinea pigs, dust reaction iod were not detectable by macroscopic examination until the 40th week of exposure. However, by the fourth month marginal atelectatic areas were already manifest, and these are presumed to be signs of glass-dust action because they appear definitely to be related to pigmented areas at a later stage. It is of interest to note also that the earliest pigmented ioci appeared subpleurally and were more frequent anteriorly, while a geo metric pattern first made its appearance causal relation between these occurrences and the experimental dust exposure. In this connection caution should be ex pressed against applying the information derived from this study too directly to the problem of the modern glass wool or glass fiber industry. Since experiments were started, many technics! changes have been introduced into the methodoi preparing glass wool or glass fibers, and the product cur rently available to commerce is considerably lighter in caliber than that used in the pres ent study. The results of a current study oo one such produet will be ccnummkated at a later date. summary toward the 138th week of exposure. Ulti mately dark green foci of pigmentation .appeared. Ip the' case of the rats, on the contrary, .ihe hztgs were remarkable for the paucity M evidence of either dust pigmentation or , reaction. Indeed, though foci of pigments. fidn appeared, these were less in evidence in , the ammals which had died spontaneously than m those serially killed. The results o( three intratracheal experi ments with glass wool aad one inhalation experiment with glass wool and glass cotton are described. Focal atelectasis was the dominant Icdofl in the animals in which the glass wool was introduced intratrachcally. The severity oi the reaction appeared iO be inversely proportional to the caliber of the glass fibrils. comment These gross pathological phenomena will he .further elucidated elsewhere,1 It would appear from die foregoing, however, that the . effect cin the pulmonary tissues ol animals oi . glass woof of the caliber and fiber length used in Che experiment is not wholly inert. While the fiber* are not fibrogenic, they do r .Appear to be trapped in the lungs, and though they provoke no macroAcopicaJly detectable ..reartio^the prevalence of`pulmonary infec tion. at $*e, rat partteuldtly and the frequency ;..wjth,which focal atelectasis was seen in the* .. guinea ptg more especially suggest a possible The inhalation experiment wM attended by s relatively high mortality from pulmo nary causes in the rat but with little gross evidence of dust reaction, lo the gunw* pig, the glass wool was observed to be focaljy deposited and retained in animals that survived long enough m the dusty environment, No macroscopic evidence of fibrosis was adduced. REFERENCE 1. Schepert, G. W, K. The SfoSogted Attkss d CUi* Wool; Stodies on Experimental Pulmonary Histopaifxrfojfy, A, M. A. Arch Intuit. Health IS:280*287, 195$. 274 DL BioLycJjtdion of QU Woo? ;W bperiartetel Mnoaacf' Hjmpetbehfy i'W. H. SCHEHRS. M.D., DJic, Snmae Lake, H.Y. The .observations flowing, respectively, from the intratracheal and the inhalation experiments described by Schepers and Delahant * wit! be presented separately. IHT*A?&ACBAL STUDY; 20*49* GLASS WOOL Glass wool is fabricated by ejecting molten One month after the intratracheal intro gi&s by means of supercharged steam into a duction of glass-wool fibers, areas of lung chamber where fragments varying from 25 'tissue are demonstrable in which the alveoli td 30 cm. in length falH During the process contain numerous multinucteated giant cells fi manipulating this product in the mania- * in which glass fibers may be found. Some rf$/6f_textiles, fragments are releasedv alveoli may contain several such giant cells, o'the jer'and have.bqen known to act as1 and in others'the giant cells are so large irritants,* but they have not . been m- as to 0 the greater part of the alveoli. The erimmaied^s a cause of pulmonary fibrosis,* smaller the fibers introduced, the larger are occasional cases have been cited m the associated giant cells. Ho free-lying I * , connection with which the inhalation ofglasswool dust has been implicated as a contribut- * mg cause of pulmonary disease of variable se- ^ -verity.'. At the meat, these reactions have . been' attributed to mechanical irritation, as glass does not contain any free silica. Pow^dered'giass has been shown to be inert for glass fibers could be observed. The alveolar walls are infiltrated by macrophage cells and occasional polymorphonuclear leucocytes at numerous points. There is, however, no appreciable hyperemia, and only isolated glass fibers have penetrated into the alveolar walls, either separately or in a phagocytesed subcutaneous or ocular tissues. The 'increasing exploitation of glass w0* and oTgiass fibers in industry and the simi- state. Many of the longer fibers appear also to have either extremity embedded in an adjacent alveolar wall {Fig. 1A). ,tarity- bfeween glass spicules and asbestos At several sites these islands of phagocytic 'Kb^fg necessitate constant vigilante con- reaction involve the lung lymph nodes, which centiiig*^w properties of these glass fibers. are considerably hypertrophied, with lym description of the pulmonary lesions phocytes overflowing into proximal alveolar f. resufting-fronTthe introduction of glass wool into guinea pig*,.lungs will serve to show r i THhat,jhough the silicon,element in the gUas walls (Fig. IB). Glass fibers arc not, how ever, found in the parenchymal lymph nodes. The hilar lymph nodes show some endo- ' is`jSresenfas a'silicate and thus does not theSokiceil hyperplasia and prominent lymph provoke the characteristic nodular disease follicles in which macrophages, with minute associated with quartz inhalation, glass fibers glass'spicules, may be found, of the caliber and length used in this study, The king fields intervening between these when effectively lodged within the lung tis affected areas appear relatively normal, sue, arc nevertheless capable of producing except for a measure of incipient atrophic quite remarkable lesions. emphysema. Recorded for publication July II, 1955. Director. The Saranac Laboratory, Around some of the smaller bronchioles the cellular infiltration may be quite abundant, 275 1 SCHEFEKS FJg. 1.---Acute pulmonary tissue reaction to long-fiber glass wool--guinea pigs: tmrairacheal injection el 20*-jD* fibers: result after one month. .4, giant macrophage filled with glass spicules, some ol which are sew to penetrate the alveolar walls and bleed vessel walls. B, proliferation of lymph nodes and extension of the cellular reaction into adjacent alveolar walls. C, ptribrontbiob? cdtutaf inflammatory reaction, with epsthelialtzation of adjacent alveoli. D, wide rone of cellular infiltration around a bronchiole, which is distorted and linked to atrophic alveolar ducts; degenerative changes in adjacent vascular bundle BIOLOGICAL ACTION OP CUSS WOOL and the fining epithelium shows considerable hyperplasia, with some superficial desqusmacos. Very occasionally, glass fibers may be seen adhering to the surfaces of the bronchial epithelium, but there is do mucosal reaction to their presence. These affected bronchi and bronchioles occur in proximity to the islands of 'parenchymal reaction <Fig. icy. At isolated sites there is a broad reactive cellular zone around the smaller bronchi, which completely obscures the pulmonary bistioarchitcctonics. The trapped bronchus may be distorted and distended (Fig. !). The tracheal epithelium tends to be somewhat hyperplastic and is covered by a thin layer of exudate which contains polymerphonudeaf leucocytes. Two months after die introduction of the gta-woo! dust, much of the reaction seen within the first month has receded. There now are fewer parenchymal Islets in which glass-filled macrophages occur within the alveoli. More frequently, these macrophages are to be seen diffusely scattered throughout the lung tissue. Isolated foci of intense, and even confluent, interstitial cellular infiltration also occur. atrophic alveoli, and the larger, fibers are to he found m the alveolar walls. The bron chiolcs show some superficial epithelial dev quamation (Fig. 2A). Occasional bronchioles may be. trapped within hyperplastic areas and appear stecosed These areas differ from those demon* strated after the first month in that there axe many more fibrocytcs than inflammatory cells and the tissue has a poorer blood supply {Fig. 28). In the lymph nodes, the glass is now condensed into formless focal deposits, with no evidence of macrophages but with some cellular condensation around them (Fig. 2C). The lymph codes of the lung parenchyma are normal once more. At the end of 13 months, the interstitial parenchymal reaction may yet persist but now minimal in degree. Glass fibers arc now but scantily represented and occur mostly in the alveolar macrophages. Some glass rods may, however, be displayed within the interstitial tissues, and some arc still seen to transfix aivco&r walls. The main afess?mality now concerns the bronchi sod bron* chioles which tend to be regionally distended and display many crypts and papiSae cov* * A new feature is the abundant presence of eosinophik cells within the alveolar walls, fhe peribronchial or perivascular tissues, and also sometimes within alveoli or bronchiolar iumina. The bronchi and trachea show no material pathological deviations at this stage. The lymphatic reaction has become modified, and the lymphocytes nowoccupyperivascular artd pericapiliary positionsmainly. This change is fairly diffusely disseminated, The hilar lymph nodes show no further reacJjon. d by s thin lining of cuboids! or squamous cells. This bronchiectasia and bronchioiectask had already commenced at 12 months, but the crypt and papillary formations are later trends. The condition is more marked wiffi exposure to the shorter, narrower fibers (Fig. 2D). whalatiok expekke*-?-. <* kho less mzts The essential difference between the result the Introduction of glass wool by means of a sfe*fe intrairadreri injection and the slower inhalation of the fibrous particles under experimental conditions is quite strik- At the end of !2 months, a considerable amount of glass still persists within the lung tissue, and there are isolated islets of confluent cellular pneumonitis. More of these fibers are now to be found within the interstitial pulmonary tissue in ateas where such proliferation persists and such fibers tend to be relatively long. Generally the short "& There is no acute response of the bronchial mucosa to the inhaled glass-wool spicules which impinge upon its surface (Fig. 2A). Very little reaction occurs before the fourth month, whereas m the intratracheal e*perimem the maximal effect is achieved within the first month. By the fourth month ! , . ^-rO}ni5 pulmonary reactfcwte kfr.fibcr glass wool-gumea pigs: intratracheal ",**< ?/ fibars: result at 12 waofat- perauton Jomtnaatfy ccBulsr reaction i> I'#. >i . .. < 2?% BIOLOGICAL ACTION OF GLASS WOOL Fig. S--Early response to inhaled shortvfiber glass woo!--gubet pigs: inhaiaiioe stud? of Jess than 6* fibers. A, presence of gi-:?*wool dust within a bronchus on the Jfeh day. showing absence of immediate reaction. B. cellular infiltration of alveolar walls, with hyperplasia of parenchymal pulmonary lymph nodes {reaction at four months). C, epithelial hyperplasia and peribronchiolar fibrocellular reactIon, bringing about progressive narrowing of the lumen {reaction at four months). V. epithelialtcation of Ibe alveoli adjacent to a bronchus (reaction after a year). SCHEfiBRS These are separate cells, and ihwe is very effect (Tig. AA). A considerable degree tittle oi a tendency to giam^ccll formation. of bronchial epitbefia! hyperplasia has super EosiecphiJes are fairly. numerous now, vened, and the lining shows marked rugoat? whereas. they appeared fetw stmly in the btraCrache&l experiment. Glass fibers, on the contrary, are very scant, and because the inhaled substance contains fibers less than 6* only, they ate limned to short spicules, all of which ate intratritelar. En the lung parenchyma, tiiere are patches of almost solid, cellular reaction around the lymph nodes wltose proliferating ceDs over do* into adjacent alveolar walls, while the presence of large numbers of macrophages within such alveoli contribute to the impres sion of a diffuse pneumonitis (Pig. 3F). "There is no hyperemia. The hilar lymph node? show no particular reaction. In tiw bronchi, there is considerable epi thelial hyperplasia and cellular desquama tion, a&d a tendency to papilloma formation U present In the smaller bronchioles,. with cnucosal hypertrophy in the larger air pas and incipient metaplasia. There is no ulcera tion or submucosal infiltration (Fig. dF). The parenchymal islets of reaction are composed of thickened alveolar walls, with muitirmcleated giant cells and macrophage* occupying the majority of such alveoli and containing many glass fibers. Occasional eoainophik cells are ta be seen, but there is no hyperemia ot ccllageftosis (Fig. 4C>. In the vfeitmy oi lymph nodes, there h considerable dissemination ol lymphocytes iitta adjacent alveolar wafts. Many blood vessels also are ensbearbed m fairly thick col: feecoos of lymphocytes. Some such arteries show medial myohypertrophy. The hilar lymph nodes arc enlarged, owing mostly to medullary endothelial hyperplasia and iofiltration by means* of macrophages, many of which contain glass fibers. sages. Ttere tends to be marked peribron By the 13th month of glass-wool dusting, chial cellular mbitradon st this stage, with the pulmonary tissue pathology ceases to & evolution of multiple bronchial glandular reveal any significantly new features. cysts and mucosal papillae. A tendency tawafd feronchtectasia and bronchioJeccasta has commenced (Fig. 3C). &y the end of nine months, glass fibers commence to make their appearance in dus ters vvfchSn alveoli as well as in the koaiopheres, The bronchiokr crypts are more prevalent, a3 there is fairly considerable peribronchial and perivascular cellular in filtration, with some collagen deposition. A year after the commencement of the glass-woo? tfrtjalaticn experiment, the guinea pig lungs show a bronchitis and bronchiec tasis, wkh marked local cellular pneumonitis. The bronchial (bronchioiar) disease con sists of epithelial proliferation snd distention of the lumina, with extension of the bronchiolar epithelium over the walls of the proximal alveoli. This produces a very characteristic lesion, comprising a dilated bronchiole .sur There Kill is intense alveolar wall thicken ing due to macrophage and plasma cel) in vasion, and there is aho almost universal minor capillary hyperemia, with conspicuous perivascular macrophage infiltration. In nu merous areas there u merely abundant intraalveofer macrophage formation and no alveo lar wall 7caction of any consequence (Fig. AD). The parenchymal lymphatic tissue still escapes, even wfum lymph nodes may be almost completely surrounded by an exten sive accumulation of macrophages. The bron chitis persists and comprises mainly epithelial hyperplasia, with increased goblet-ceil activ ity and cellular catarrh, and there is also con siderable peribronchial cellular infiltration. Glass fibers are present everywhere. In stained sections they may be difficult to see, rounded by a aone of epitbefialired alveoli but scattered giant cells arc to be found (Fig, 2V), A fibroceliular reaction about within alveoli. Dark-field examination of un these bronchi may enclose such epithelialized stained sections show* up the universal dis alveoli, creating a spurious adenomatous tribution cf the glass to good advantage. BIOLOGICAL ACTION OF GLASS WOOL Fig, 4.---Chronic reaction to inhaled short-fiber glass woo!--guinea pigs: inhalation study of less than 6* fibers. A, peribronchial fibroceliular reaction which has surrounded epitheiialized alveoli, thus producing a spurious adenomatous appearance (reaction at one year). B, hyperplasia of bronchial epithelium without inflammatory reaction in the mucosa {one-yar result), C, fcca! parenchyma* cellular reaction, with alveolar wall reaction and macrophage catarrh (one*year result), D, giass-fibf'"filled macrophages, occupying alveoli whose walls show no significant reaction {result at 18 months). 281 SCXEPB&S observation in relation to oncogenesis needs These irhralxacfrcal and inhalation studies further clarification. ; with glass wool have ccRftaned^Iajrly con clusively that glass is cot fibrogenie vibes retained in the iaag'ttaue. At the same time the gravity of the type of bronchia! lesion provoked necessitates caution in dismissing glass wool as innocuous. Indeed, it should ' be regarded as a potentially harmful sub- SUMMARY AND CONCLUSIONS When introduced Jtitrairache&lly,. tongfiber, medium-caliber glass-wool dust pro vokes early marked bronchiolar damage, which persists for more than a year without leading to well-defined fibrosis. nance in dreumstances leading to the inhala tion of large quantities of the type of prod* uet studied in these experiments. Other Some of the glass wool is transferred to the hilar lymph nodes where It accumulates without inducing local fibrosis. modem types of glass wool or fiber glass Inhalation o! short-fiber, medium-caliber may not have any comparable effects. gius wool produces a retarded pulmonary In several respects, the polsrioaary reac tion to glass wool is sinnbb to that produced ; by asbestos fibers, which the glass spicules reaction, comprising partly an interstitial pneumonitis but dominantly aft endobtonchiolar and peribronchiolar lesion. resemble. However, despite the prominence A tendency toward bronchial epithelial of glass spicules in the King tissue, no "glass- hyperplasia arises under the infiuetice of pro " wool bodies'' were observed which could be longed short-fiber, medium-caliber glass-wool c compared to "asbestos bodies.* St is there- inhalation. . fore not the shape alone; of the asbestos fiber ' ^fjich leads to' the formation of asbestos bodies. .... It is to be noted also that asbestos fibers are intensely fibrogenic, whereas the lung , tissue reacts to the glass fibers by means of - a cellular response chiefly. This contrast again emphasizes the fact that the physical resemWattces between glass wool fibers and asbestos do not determine fhrir respective 'patfo^i^ propensities. Obliterative damage te the bronchioles REFERENCES 1. Dhera, V.; Vvnfonm'de la fibre de verre, Arch, m&l protest. ?:39-Zk 194$. 2. Pellmr, and Cou&n, J.: U dernuxose de la lame de vrrre, Arch, mat profess. 7;23-2? 1W6. 2 Roche, L.: L danger pulmouaire dans 1'lndMtrie de* fibres 6e mre, Arob. mal. profess. 7:2*28. J946. 4, ICahlau, <5,*. Tbdttdw Pnetiroonie such Classtaob inhalation dutch Ver*beitUfiR eines Ktssslstoffes aus Claswolfc, Frankfurt Ztschr, :143- and the proliferative reaction. of the bron- ISO, 1W. chiolar and bronchial epithelium are ob 5. Schepers. G. W, H, and Delahant, A. S.r viously the. more important._lesions caused ,-by *h glass wool. There is. but. a limited !,r^ngfi.of substances which;can provoke, epi^ theliftl hyperplasia iu experimental animals, ..and .the specific effect of glass wool thus . extends. the list. The significance of this An Exberaaemal Study of lha Effects pi Glass Won. on Animal Lungs, A. M. A. Arch. Indast. 'Health 11:276-279, I9S5. A Schepers, C, W. H.t Tiw Biological Action of Tungsten Carbide and Cobalt; Studies on *periffwntai Pulmonary Hutopatholcgy, A. if. AArch. Indus!, Health I8U4M46, S9$k <-_> . >-' 2n A Critical Utb* W. R. FRANKS, Taront*, Outada The use of animals for the biosssay of dust hazards offers certain difficulties which arc peculiar to the pneumoconioses, St, established that the hazard to man of aoy particular dust depends oa a number of factors. These include the chemical and physical nature of the material, its concen tration, and the length of time over ^hich the exposure is spread; in the atomic age radioactivity has also become recognized, Jo addition, the incidence ol acute and chronic infection superimposed upon primary lesions may alter significantly the actual hazard. Since any one of these factors may be de finitive, it is obvious that the bioassay of the total hazard to man becomes more complex than the controllable assay of such materials as drugs or hormones, for which well-defined methods have been worked out* It is not surprising, therefore, that the accurate dettRntn&ticn of the even more complex inter action of various modifying nmechanisms, be they accentuating or antidotal, requires even more care. Despite these difficulties, if is obvious to anyone reviewing the literature within re cent years that laboratoiy experimentation has greatly enhanced our knowledge of the subject. Any danger from the possible mis interpretations of these findings from a prac tical stastdpqmt true* fmea the to. that, we have seen, we are usually dealing with a Rtcotded for July U, 1SSS. Ranting and Best Department of Medical Re search, University of Toronto. 'References \ 2. Dumber of often unrelated factors, any one of which may vitally influence the dimensions of the hazard. These may likewise empha sise independently species-difference in sus ceptibility. In addition to these etiological complex ities, the clinical nature of the resulting mor bid slate may vary considerably, even with the same material. Thus we may adopt as criteria of disease such widely diverse effects as the following: bss of physiological func tion of the lung resulting in limitation of ability to carry on woric; intimate nature of the pathology produced, e. g., camifas tioo, fibrosis, or necrosis; or susceptibility to intercurrent infection, with prejudiced outcome or, even more recently, the develop ment of malignant new growth. All these clinical cod-points have been used in the experimental assay of various dust hazards. It is, however, noteworthy that survival per $e has seldom been adopted as a criterion. Apart from clinical experience, a gamut of species of experimental animals has been used. These range from cockroaches to human criminals (their use has been sug gested). To make interpretation even more difficult, a further gamut of methods of test ing has been employed. In addition to dust- rag, materials ..have been introduced into veins, trachea,* lungs, peritoneum, eyes, testes, buccal pouches of hamsters, and sub cutaneous tissues and given per os. Studies have also been inducted in vitro on tissue culture*. Ml tijtse methods have yielded useful information toward solving the prac tical problem. They can, however, provide conflicting information if due notice is not taken of the conditions governing the ex periment. ) 283 FRANKS It is obvious from a practical standpoint that the active moiety of any duH wist be -contained is that fraction which penetrate* into and is retained in the lung otthe workerConsidering first the physical attribute* of the aerosol, such attributes as partide size, particle mass, and particle shape are in volved. It is possible that electric charge, temperature, and color (photophoresis) may play some role in dust mention, but these have been generally assumed to be negligible. Radioactivity is certain instances is ol im portance. Tbe interrelation oi sire and specific grav ity has been well considered recently by Wat son* The possible importance of particle shape is wei illustrated by the extreme case Df asbestosis. There can be little doubt tbar tbe longest dimension of the asbestos fiber that is retained is tbe lung is several tunes greater than the similar dimension lor more symmetrical dusts. Returning to the problem of animal ex perimentation, we cannot help but be struck by the relatively good agreement that has bees found in regard to the size distribution ci dusts retained in the lungs of man as com pared with the various experimental animals that have been studied, this despite tbe rather Urge diStiewe Is gross anatomical dimen sions among species. This agreemoTt may be an expression of anatomical consistency is microscopic tissue design, since tbe lung alveoli perform essentially the same function in the various species. .Alveolar deposition of dost of various sizes--human data compared vwnal data Cwvc } {man) Brown, Cook, Key, and Hatch, 1950 (china clay). Curve 2 (man) Wilson and la Her, 1948 4 <NaJ4G). Curve 3 (man) Ei*abod alter Uii&bi, S*SS` (tripfcenyl phosphate). Curve 4 (mouse) Shoshkes, Banfield, and Rosenbaum, 195G,S (tom oil). Curve S (guinea pig) Palm, 1954* (various dusts to give range). Curve 6 tmeokey) Palm, 1954* (various dusts to give range)- 284 SUSCEPTtBUJTY OF ANlUASS TO OUST To illustrate this comparison, the findings of a cumber of investigators who have exsauced the jwobSem in mao or in laboratory animals have been superimposed is the Fig ure. The curve of the per cent huourt lung retention of particles plotted against.thrir size was determined by Wilson and a Met * Further corroborative data of this con sistency of behavior are gives by the findings of Barrett, I^win, and Seism00$ u with the use of cadmium oxide fumes of estimated s*ean particle diameter of 0-V Using as criterion the chemical assay for cadmium retained in the lungs, these authors found by using Na**0 mists dispersed in glycerin that "the average percentage for retention and estimating their expulsion by measuring over a wide range of dosages is remarkably the radiation. Brown, Cook, Ney, and constant for all species tested and amounts Hatch* studied the retention of china day to about 11 per cent" as measured 24 hours in humans and measured particle retention after du*t exposures which varied from 15 by comparing the changes in dust concentra to 30 minutes, The species studied included tion in the alveolar air as identified by the mice, rats, guinea pigs, rabbits, and monkeys. CO3 concentration of various fractions of As pointed out by Palm * this species con the expired air. The third human curve it sistency of retention is limited only to tb based on that recalculated by Escnbud* fraction of the dust which is retained over from various data of Landahl aud associates7 a period of rime. That deposited is nares and using triphenylpbosphaie tlouds and esti the upper respiratory tract does not show mated similarly by measuring the concen this degree of species agreement, but since- tration changes in alveolar air fractions. It the latter fractious are generally not retained, will be noted that the latter data show a they are not therefore concerned with the considerable discrepancy below 2? in size as development of the pneumoconioses. compared with the other observations (con sult Landaid and associatesr for discussion), although good agreement is found with fee remainder of the curves. This discrepancy is considered to be an artifact by PaUu 00. the grounds that the periods of observation in Landahl's experiments were too short to It is obvious, however, that only that frac tion of the dost deposited in the alveoli which is retained in the long over an appre ciable period of time is capable of playing any rigm&cazrt role in fee development of pneumoconiosis, with the possible exception of acutely toxic dust of of materials that are allow equilibrium to be established. carcinogenic or radioactive. The information ft will be noticed that these data agree available on the score of eventual dust re essentially with the earlier findings of tention is less complete. Cember, Hatch, Drinker, Thomson, and Finn,* who found a Watson, and Gfueci ** have reported on the total tetention of approximately 55Jo of fate of particulate radioactive barium sulfate dusts varying in sire from 0.15** to Gp, i. t., injected as a hydrosol intratracheally into within the size range titat is chiefly concerned rats- Each anhnaV received 0.55 cc. of fee- in penetrating into the lung alveoli. mixture containing a total of 25.7y of BaSO. The findings on human subjects are com pared with those obtained in animals in the Figure. The latter include the data reported by Shoslikes, Baaficld, and Rosenbaum " using com oil in mice, and by Palm * in guinea pigs and monkeys using china clay, carbon black, antimony trioxide, and dark clay of various sizes equated for difference The curve of retention of the material wife time showed an initial rapid disappearancewhich was complete within approximately six Hours, This phenomenon was interpreted as being due to elimination by the dliaied epithelium. The rate ol disappearance oi the remainder which was considered to hsvepcnetrated to fee lower respiratory trWt ifi densities by conversion according to equalled approximately one-fifth of the ma Stokes' law. On the whole, the agreement terial per day corresponding to a half-life between the alveolar deposition in the vari of 3.5 days. These authors remarked that the ous species, including man, is striking. latter rate is more rapid than expected. Fur- 385 FRANKS ther data have been supplied by Palm1 who marked silicotic lesion, might have been fore studied the clearance rate from the lungs of told. These negative results confirm the guinea pig* of inhaled antimony trichloride validity of translating animal test assays into dust, .s. g, 5A in diamttet. The animals human terms in regard to a given dust when were exposed for 12 minutes to a concentra lung penetration may be the single limiting tion of the order of 100 mg. per cubic meter. factor. The guinea pigs were killed at various inter From the foregoing it is possible to make vals ap to IS hours postdusting, and the dust a rough calculation of the actual amount of retention was measured chemically. Palm's dust retained by the lungs of an animal results agree with those of Cember and asso when exposed to a given dust. For example, ciates17 in that there is an initial rapid loss using First and Drinker* figures M for dusty of material from actual "Jung" samples which mine air of approximately ICO mg, per cubic is more or less complete within six hours. meter (3 mg. per cubic foot), equivalent to This author likewise infers that this repre something of the order of S,000,000,000 sents the removal of material winch bad nor particles less than V * diameter per cubic penetrated beyond the area of ciliary action meter, it can be calculated that a 250 gm. and makes the point that, to estimate the rat that breathes approximately 50 liters of true alveolar deposition, a six-hour holding such aft atmosphere in an right-hour day period should be allowed after the dost ex would inhale about 5 mg. of dutf. Of this posure, The disappearance of the antimony size range, as we have seen in the Figure, after 6 hours is likewise at a slower rate, and something of the order of 30%> would be the point on Palm's curve foe 18 hours agrees retained in the alveoli. A rat would thus be very well with the MJb retention figure required to handle approximate^ 1.5 mg, of found by Barrett and associates " with the material within the space of a normal eight- cadmium aerosols. The data of the latter hour day's exposure. This dose rate, al authors hx> included rats and rabbits. We though approximate, serves to orientate our may conclude, therefore, that the relative thinking when it comes to the experimental agreement of eventual alveolar retention study of the biological hazard of any parrie- among various species may legitimately be tilax dust. extended to include these types as well. Pats, In the bioassay of a human dust hazard by guinea pigs, and rabbits thus behave similarly means of animal tests, the physical limits of on this score. the mechanical methods of lung clearance, On the whole, therefore, wt may conclude be they by ciliary action, by exudate, by that, as compared with man, Ovt alveolar dust lymphatics, or by phagocytosis, must be con retention of various experimental animals sidered. The available data leave much to be shows a reasonably good agreement, at least desired. AU the above references include to the first approximation. This would indi tests carried out foe relatively short periods cate that, from the standpoint of dust men of time. Undoubtedly, if an occupational dust tion, various animal dnstmg experiments hazard exists, the duration of exposure is might be expected to yield relatively reliable, one of the dimensions of the trauma. Little data in terms of the human equivalent. The teal evidence of the relative behavior of man variations among the various species studied and various test animals Is available. and the human are not much greater than There U, however, abundant information that reported, for example, by Lsndahl and on the size distribution of particles found is* associates' foe various humans under vari the silicotic lung, which has been culled from ous breathing patterns. human postmortem examinations. All this It thus becomes evident that the human mfurmaricn agrees remarkably well with the experience with natural dust with particles findings on animals in the relatively acute greater than 10/< in diameter, such as in the experiments stunmsrited m the Figure. Sahara.'* which fa I to produce a svell- Nevertheless, it must not be forgotten that 226 SUSCEPTIBILITY OF ANIMALS TO DUST the actual dust exposure is measured by the balance of dust deposition vs. dust removal jo the long over a period of rime. 'When we with each other; yet when it came to meas uring the actual toxicity of the material retained, the L. D. varied from 500 min realize that Cember and associates ** only followed a single injection of 28? of material in the rat lungs and that Palm's exposure* only lasted for approximately 12 minutes, involving the probable deposit of a similar utes per milligram per cubic meter exposure for rats to 30 times that figure for monkeys, with other species ranged between these extremes. Only mice and rats showed evidence of an agreement within 100% of amount of material (30?), the need for cau L. D. dose. tion in applying these results to the long term problem becomes evident. These re marks likewise apply to experimental studies where amounts of material of a converse order of magnitude have been employed, eg., 1000 rimes or more.** The difference of the effect of inhaling various chemical dusts as among species usually depends oq differences in systemic susceptibility to the poison rather than on differences in the local lesion. In order that any great confidence may be placed on re As important further parallelism between sults with animals, preferably at feast two experimental animal and human behavior in criteria should be met, namely, first, the respect to dust retention is to be seen in the fact that the lung in neither case ever comet into equilibrium with the dustiness pathologies! and physiological nature of the resulting experimental lesions should closely resemble that found in man and, second, of the environment during a normal life span. This is well shown in the case of humans by the findings of Belt and associates M who there should be a demonstration that the lesion produced is predominantly local in character and not due to the systemic ab showed that the amount of residual ash re sorption of a poison. covered from human lungs increased con It is obvious that uncomplicated silicosis tinually with age. Experimentally in animals is an example of a human disease that largely it has bees a universal finding that the fulfills these criteria. The experimental le amount of dust retained in the lung in sion produced resembles closely that found creased progressively with duration of ex clinically. The course of the disease in dif posure, even in experiments where the dust ferent experimental animals is comparable concentration must be regarded as excessive within close limits, and the disease is largely by any standard. The eventual limit of lung limited to the local lesion. capacity to retain dust has yet to be discov There remain, however, the possible dif ered. ferences in the influence of the time factor, When the chemical activities of various dusts are considered, the dose response of various animal species, as is well known, may differ widely from that for man. Teleky ** has been prompted to conclude that as I have pointed out. We have generally assumed that the rate of production of a silicotic lesion in the smaller animals is more rapid than in man and is possibly somewhat akin to their relative metabolic rate. Well- the value of animal experiment1; has been paired quantitative data, on this score are overestimated in determining the human hazard and points out that indiscriminate deduction from animal experiments can be misleading, citing differences in lead sus ceptibility among species as an example. There can be no question but that this criti cism is warranted, unless due caution is exercised. For example, Barrett and asso ciates11 found that cadmium dust retention lacking. The relative metabolic rate of rats, guinea pigs, ribbits, and man is in the pro portion 90 to *80 to 45 to 25 Cai. per kilo gram per 24 hours, respectively. It thus will be seen that the rat metabolism is approxi mately twice that of a rabbit and three and one-half times that of man. If the rate of development of the silicotic lesion were directly proportional to the metabolic rate, by various species agreed remarkably well there would an obvious advantage in 287 4 PRAXKS using the smabest axums? that will give a iu the experimental assays differs widely, characteristic response, i. e.r the rat or the and their relative sign?Seance among species mouse. However, it has begun to be recog cannot be stated with certainty. nized that this relation may not bold, is It would appear, however, that by the use view of tiie accumulated reports of acute of suitable animals a reasonably .reliable silicosis developing in mas under toodvuorvs measure of the dust fraction actually de of extreme dust exposure and the realisa posited in the lungs of workmen could be tion that in most experimental situations the inferred from animal exposure to the actual animal exposure has been of an order far beyond that occurring tn industry, both in respect to time relative to life span and to atntospheric concentration. The intratracheal insufflation within the space of a few min utes of even 50 mg. o silica dust into a 250 gm. rat constitutes a trauma equivalent io approximately one month's exposure of tight hours daily to a dust equivalent to 3,CCQ,000.000 particles per cubic meter. Ytt ibis accentuated dose rate even in a rat re quires approximately live months to pro duce >; weft-defined silicotic granuloma-18 Wlten we consider the dimension of this degree of insult both in concentration and in respect to amount and time, these rates M development cl the silicotic lesion are not so far out of Une with reports of acute silicosis that has developed in mart under conditions that approach these in severity. There can be no doubt but that the acute experiments in animals have provided use dust conditions. If it can be established that the role of development of silicotic granuloma as among species is not propordor<ate to thrir respective metabolic rate, then indirect evi dence wifi have been produced that the meclianism of the silicotic lesion is probably through an extracellular reaction or at least one in which some other factor than the re action between the silica and the rate of production of any metabolite is concerned. Is ihe development of the simple silicotic lesion, the phagocyte and the fibroblast prob ably are the chief cellular structures con cerned. In this respect it is noteworthy that the physical dimensions ol these cells as among spedes show relatively Bute varia tion. The rat monocyte and the human analogue are essentially the same sire. If these similar cellular elements remain dimen sionally constant, it b not surprising that ful information, particularly when compar such factors as particle size appear to play able materials are being compared, but such a similar role in various animal experiments results must he regarded as qualitative when and in man. The size of dust particles which applied to the actual industrial problem. are found to be active m a rat f is similar Aciuaily tittle work has been done on animals to that found clinically at postmortem exam* with exposure to dust concentration which mation in man. An unfortunate circumstance, parallels the majority of human exposures which undoubtedly plays a role in the de today and which show clinical signs of velopment of many of the pneumoconioses, producing rilieosis. In fact, King and asso k that the particle sUe which penetrates to ciates l$ have shown that with the insuffla the vulnerable tKmciliated alveolus is likewise tion technique little frank rilieosis can be of a size which is "biologically" active in re produced tn the rat within the normal life lation to the phagocyte and other host cells. span ol this animal with doses of silica dust such as are liable to be inhaled by even the dustiest trades in the %M of modem venlilaricn procedures. Are we eo conclude, therefore, '.bat these measures Have removed entirely the hazard to man? The answer from the animal experiments, unfortunately, Reverting again to silicosis, it <*n be said with considerable assurance that, if there are differences among species in respect to their tolerance of any chemical activity of silicotic dusts, then these differences are probably small. is not unequivocal, because the time factor f References JS arid J9. 2SS SUSCEPTIBILITY OF ANIMA1J TO DUST There is some qualitative evidence f of response can be measured. At species difference as shown by differences tempts to estimate the degree of change io production of ashestotis bodies experi microscopically have been carried out in a mentally. Thus in the classical experiments number ol laboratories, but all are subject of Gardner ** h was found that the formation . to the judgment of the observer. The grading of asbestos bodies encountered in the lung of the experimental silicotic lesion on a 1 of guinea pigs in every way resembles the to 5 basis of the Hammersmith school well golden-yellow beaded or haustral rods pic illustrates this point.'* Undoubtedly this tured in human cases. In the rabbit, how procedure is useful in judging results, but ever, bo typical bodies were found, and in no one suggests that the development of the the rat this occurrence was extremely rare. pathological process proceeds in a stepwise Since there is good evidence that the develop manner. ment of these bodies depends on a charac teristic milieu, these differences may be taken as a qualitative measure of difference among One cannot help but be impressed, there fore, with the usefulness of the recent de velopment of a method by Aterman * of species. This phenomenon is quite possibly estimating by quantitative chemical means rebted to the degree 0f hydration or reaction the amount of collagen deposited in a given between the host tissues and the dust. Gard tissue. The application of this procedure to ner considered that this lack of reaction in the study of the pneumoconiosis which is the rabbit was associated with at least a characterised by collagenous deposits, either delay in the production of fibrosis from the within the lymph nodes, in the parenchyma, dust, as compared with the guinea pig. or even in the vascular tree, should provide When the tote of superimposed infection a ntw dimension to Wtt study ol these dis is considered, the difference among spedcs eases, as Stacy and King have been quick susceptibility again becomes evident and to recognize. The method apparently is capa makes difficult the accurate laboratory assess ble of providing useful information even in ment of a clinical dust hazard. However, as retrospect, since it itwy be applied to tissue the classical experiments of Gardner with samples after fixation. Similar methods to the tubercle bacillus superimposed on sili measure other parameters of the pathological cosis have shown, the effect of the latter may response to dust exposure would be welcome. in many respects reduce the species variation As might have been expected, the influence in regard to the former. of dustexposure load rates on the develop Similar remarks might be made concerning ment of pathological lesions in the lung be other pathological complications, such as the comes increasingly evident when the rote development of lung carcinoma. Species of antagonistic substances is being studied. differences in the ease with which this dis In such circumstances relative rates can ease can be induced experimentally are well become definitive. Thus io the experience known. It is now evident that real differ of King41 it was found that the influence ences can exist even with different genetic of powdered aluminum in preventing the strains within a given species. development of the silicotic lesioss was not In the bioassay of any response, it is axio matic that mote information U to be gutted if the results can be measured quantitatively. The mere recording of the presence or ab sence of silicotic nodules following a given dust exposure does not yield as much in so apparent following a single intratracheal injection in.rats as compared with the find ings of Denny and associates44 using dust ing. The further finding that aluminum oxide is active under the former conditions of ex perimentation accentuates the point.4* Ani formation cither in regard to the nature of the development of the process or of the eventual dimension of the hazard as can be gained from criteria in which art accurate mals which receive at one instance a dose of dust similar to what would normally be spread over a period of weeks, even in a very dusty atmosphere, are presented with 239 FRANKS a challenge which may differ significantly when measured in relation to an antidotal process which may in turn have t#e* limiting factors of relative solubility, motecufar diifusion, adsorption, or even chemical inter action. The conclusion to bo drawn from such experiments must of necessity be limited to the condition of the experiment and ifetrafei'the fact that, when jiving processes are being studied, the one relative to the other, dose rates may be critical. In the last analysis, the process of dust Inhalation and retention would appear to be one of the essential dimensions of a pneumoconiosis hazard. logical efficacy of such substances depends on dose rate, REFERENCES I. Roach, S. A.: Method of Relating the in cidence of Pnewnoconrosis to Airborne Duu Ex posure, Brit J. Iwhist Med 10:220, 1953. Z Wright, B. M. *, Importance oi the Time Factor in the Measurement of Dust Exposure, Brit. /. Indus*. Med Iff:235, 1953. 3. Watson, H. H.: Dust Sampling Jo Simulate the Human Lung, Btk. J. Itvdust. V4, l$v93,1953. 4. Wilson, I. B, and la Mer, V. KL; Relent!on of Aerosol I?ankles in Human Respiratory Traci as Function of Particle Radius, J. Indus*. Hyg. & Toxicol :26S, im conclusions ;*li Available data would indicate that there i#**a reasonable agreerfient iurtdng various ahinasd aridJ^fosnan Qscdies in Vegard to The dustreiaioctfm the'lung. The'use of experi- nsisrttV anfmSs'in the blossiay of* dust haz ards'Would therefore appear to' be valid in th&r&jfect. . . 2...0e to.large species variation, however, 5. Brown, J, H.; Cook, K. M,; Ney, F, G. and Hatch, TV, Lrv6ww:e of Particle Sue upon Retention of Particulate Matter is the Honen Lung. Am, j. Pub. Health :4SQ, 195Q. 6. Eisorfnid, .M.::Retention, Distribution afld l^tnurtation of Inhaled Partictstaes w'rth particular Reference to. Evaluation of Radiologic Risk, A H. A. Arch. Indust Hyg. :2t4, 19SZ 7. Landahl, H. D.; TraceweJJ, T. N., and Lassen, W. H<: On fee Rci<raft of Ait-Bonw m , regard, bofe, to..tbe .Uix]ity. of various substances and iQ .the;TeUtw susceptibility jo concomitant infection, animat bioassay erf industrial hazards has to be interpreted with caution, 3. Neither m man ridr in experimental stutriafs dbeS tHe lu&g tome info equilibrium ^tlrjh^ustiriftss <>f tfti environment. The P&ftieul&tes* m the Human Long, 0, A. W. A. Arch. Indust. Hyg, 1*359, 1951. & Palm, P. E: Thesis, University of Pitts burgh, 1954. . P Drinker, P.; Thomson, R. M., and Finn, J. L.: Quantitative Measurements *A the lohalatroo. Retention, and Exhalation of Dusts and Fames by Man: f..Concentrations M 50 to 4SG Mfc per. Coble Meter, /. Indust Hyg. 10:13, 1928. cdfitMaoffg Scton^ulation of foreign materials iri lhe lung would appear to have increas ing importance with the increasing life span, A givftn'dbSt hazard must thus be judged iif^elatidfl' to the iutvival tirrit T^ative to tl^!^$uK.*bjrxtly or indirectly it, cap be anticipated that fee' pnenmoco^jose? will 10. Shoshkes, M,; Baafald, W. G,, and Rosen baum, S. J.; Distribution, Effect and Fate of Oil Aerosol Particles Retained in Lungs of Mice, Arch. Indust Hyg. 1:20, 1950. 11. Barrett, H. M.; Irwin, D. AH tM Stsftwons. E.: Studies on the Toxicity of Inhaled Cadmium: I. Acute Todty of Cadmium Oxide by Inhalacwv J*. Indust Hyg, & Toxicol 28:279, 1947. be of increasing interest to the gerontologists. 4. Newer, chemical method^ yielding, a quam*tiyeumeasure of tissue response offer effective jpes^es to.improve the. bioassay of dust, hazards, i>oth clinically and experi mentally. . : ... -$'* Where telative rates of socb factors as^aoJabiiily, diffusion, or adsorption play a tote fa antidotal activity, the apparent bio- 12. Cerober, H,; Hatch, T. F,; WatsoR, J, A, and Grweei, T< B.: Pulmonary Penetration of Particles Administered by Intratracheal Icsuffbti<m, A. M. A- Arch. Indust Hyg. 10:J24, 1954, 13. Polirard, A., and Collet, A.; Deposition of Siliceous Dust In Lungs of Inhabitants of Saharan* Regions, A. Id, A. Arch, lorfust Hyg. 8:527,1952. 14. Fie st, M. W, and Drinker, P.: Concentra tions of Particulates Found in Air, A. M. A. Ascfcv. Indust Hyg. S:387, 1952. 290 SUSCEPTIBILITY OF ANIMALS TO DUST IS. Ray, S. C; King. E. J, aad Harrison, C* V,: Action of Variable Amounts of Quartz on the Lungs of Stats, Brit J. Indust Med. 8:62, 1951. 36. Bril, X, tf.; Jnvin, P, and King; B- J.: SUicem and Oust Deposits kt the Tissues of Persons Without Occupational Exposure lo Siliceous Duets, C&nad. M. A, l 84:125. 1536. 27. Teleky, U; Uber ceuere Forschangsmethod u*d Forschu&gen auf dem Gebict der Gewwbekrankheiten, Klin. Wehosehr. 27:249, 1949. Iff King, E_ }<: Scientific Basis of Medicine, Lw>4cft, University of London Press, 1-tA, 19S3, VoL 2, p. 108. 19. King, E, }.; Uohanty, G. P.; Harrison. C> V, and Nagelsdsmidt, G.: Action of Flint of Variable Size Injected at Constant Weight and Constant Surface Into the Lungs of Hats, Brit. J. Indust. Med. 16:76, 2953. 20. Gardner, ` L. U, and Cunmangs, D. .: Studies 03 Experimental Pneumoconiosis: Vi, Inhalation of Asbtttos Dust: It* Effects upon Primary Tuberculous Infection, J- IndusL Hyg. 12:65, mi. 21, Aterinan, 3C: Studies in Fibrous of the Liver Induced by Carbon Tetrachloride: 1L A Quantitative Study of the Effect of Cortisone on Fibrous of the Liver ki Pats, A. M!. A. Arch, Path. A?: 12, 2954. 22, Stacy. B. D, and King, E. }<' Silica and Collagen in the Ltmgs of Silicotic Rats Treated with Cortisone, Brit, J. Jadost Med. 11:192, 1954. 23. Denny, J,** J.; 'Robson, W. D, and Irwin. D, A.: Prevention of Silicosis by Metallic Aluminum, Canad. M. A. J. 46:213, 1939. ,,t ^ ExperimentalEtudp ojthe Ejects $ctre Ehzrthi on ji,,anal cd?un<p$ G. W. H. SCHttTO, ->., Wfc. ANTHONY 8. OOAHfcHT end ANPKPW ftCDUN, Sereaec Ukt, N. Y, During the last few years of )ys life Dr. L. U< Gardner, then Director td The Saranac Laboratory, became wotteodwasly interested in the problem of radiological changes which were discovered in workmen from Fostorm, Ohio, who were exposed to dusts containing rare earth oxides and fluo rides. Dr. Gardner's observations led him to the conclusion that many of these shad ows could be caused by the high atomic densities of the components of such rare earths * To elucidate both this postulate and the posable biological action of the rare earths, Gardner conducted two series of experiments in which he sought to contrast the aciion'of the Jofiowuig blends: , j * , , -BlcMl' ' * ' .. .P^Otot Csito. /. ~i.. ;/,.*-s,'.vYk"" i#.. S a' eri strife ftoo*4. ./.....*<. oxldea.,...*..'.;.,...j , 7t4M&Ba- mltm ...4,....... 4 'W4* OsrPvfe....'. :..s.>< Quptiu fits* tfcrti ftscftfc*. J2;*. * |Ur Mrtb oats**:.,, r foUtsttBS * ft!(fe ,'. If, ' * r as < Recorded for ^ablk&tiea Jvdy U, 1955. ; CDr. .Scbet>ert),"ECTiich Associate (Mr. Delahsht), and Chemist (ifr.' 'Reditu)* The Saranac La&rvory. . * Hie compounds commonly included flndfr.,tbe Stooping 61 '*sare earths'* include the telemtnts Us&aaam, ctrasm, praseodymium, . neodymium, samarium, europium, 'gadaKafom. .-teifehaft dys- prosium, bohoium, erbium, germanium, .tfoUwe, ytterbium. a#d4u.tSu'm, ',5. ... . The studies with these substances included intratracheal and intraperifoneat injection experiments with both blends, which were commenced during 1943. An inhalation experiment and a study of the tuberculogeaic propensities of the latter mixture were begun during 2945. Before these investigations could be brought to a conclusion. Dr. Card* ner died. Two of us {A. B, J>. and A. J. R.) who had assisted with the project had the rapoesibrthy of completing the study. le the present account the results of Ihe infratracheal injections and the inhalation study are reported for the first time, USTHCOS For the intratracheal technique, the individual ingredients were prepared separately by grinding in porcelain bail mill for as long as was Bteeasary to obtain the desired sises, 3m and under. They were titen mixed in (he foregoing proportions and adjusted to a ltf% sospenston in isotonic The euspentlon was then &mo5di?ed a* 100 C for ose hour. A.'doss: of 1M mg. was admm&ered mtratracheaply to two groups of nine guinea pigs us two equal amounts at seven-day intervals. For the inhalation study, 75 guinea pigs were exposed to an awosol of Slend 2 in a mom measorihg approximate^ bby S by 8 it The exposure period was for eight hours dafty, and tax- half days per week for three years. Dust diwsfcm anas accomplished by (he hopper method. Bart ceocentraGoes were very high in (be early weeks of the exposure but leveled off (hereafter, to the order o 3M,0,<0 to 300,0%CCO particles per cubic foot of air, as deteimwed by Vigbt'SeW count. The eaicukred particle size Ip to 2m. i'." , ' JMSVLTS fcFor easy reference the sesults obtained have been aawnhkd iu Tables \ %o 4, Commpnts in this paper-will he limited to the 292 EFFECTS OF RARE EARTHS OR ANIMAL LUNGS TAftLfc i.--P*d*i<nary Bffedt of Rare Earlk Osid*4 Intratracheal ifeihod OgfcH Sfc w. tajwttoa r CM or EDM DP u tt 08 xr IX DP ?mx t is B + M vs tn 2$ in Dt Mm E 8 *0 a Grot* PttJaooaefr Beaeuea 0aUM vfu clock k.ts* eoeatMoerat* *e4aBafierta*Ba 04QACAW6 Wfe A tbfk lere* eoMlnnerAW kewn CEestd ltA Ates of (otHUdaUM isfl a etajffe coocXotsentte teca 0*e Um pkek mo. tteto*r*u hofee To KttjJoatrA* kioea wfu Ciflaet OWk ^fpRBtetioa Soft blark eonaX*rt Jotioa Soft Wftfli nbpkonj ftaxeuuaa L*tt* eoafoAMnte keAieji <*ub coashA&n* wetun Qm lartt&Mek tott eca- (XoDe'ACe Map anti ovo^lt* ^corM aj. WAtoo *Dw3 a/Ur teeoad istaruop. D>--EMcd el po*uo*l*, Ite-tt" ol l>pbM. a-jHiiq. gross pulmonary features which were tecorded at the time of autopsy. The analysis of nacrosccpic features win be presented elsewhere^ Reference to Tables 1 and 2 indicates that three of the guinea pigs died of pneuawnia shortly after receiving the first mixture, in which there was a relatively high proportion of rase eanh oxides, whtie lour died simi larly though after a slightly greater interval xn the case of the mixture with the high rare earth fluoride content, ft seems likely that dine pneumonic casualties may have been at least partly aserihabk to the chemi cal substances introduced. The remaining animals survived the initial presumed trauma associated with the intro duction of the foreign matter, Two of the animate from the fiist group and one from the second experiment died subsequently from rodent typhoid which decirttated the ani mal population of The Saranac Laboratory f References 1 and 2. at the beginning of the winter of 1944-45, It is a sigzrifKaot fact, though, that animals survived to the end o{ the experiment, J. e., 540 days after the first injection. Macroscopic inspection of the lungs re vealed the presence of large, black, soft to slightly firm conglomerate ksioas. These masses, which were commonest in the caudal lobe, were usually well circumscribed. lo addition, an occasional animal exhibited small discrete foci of black dust pigmentation b<iteath the visceral pteora. Few differences in the character of tbe te&kms were seen grossly in any of the animals in cither group over the entire 540-day period. Nor were there any metastatic foci of reaction in any other rg*st, though some of the dust had become deposited m the ovedi&siteai tissues and pleural space in isolated instance* in a manner suggesting minor pleural ruptures at the time of the Intratracheal injection, la the case of the inhalation experiment, the casualty raw was comparatively high. Taslk Z--Pitlne**ry Efttti of Rare Edrth FIhdtvUs Intratracheal Method OulDM Dat Ptt*. Wo. IrUaettofi ir* U sw x&s Ov U Dp * DO t>P x X w tT5 w n ST MO MS E*. > S l y X k fbJaentry JteieUoa OaMvrttu) *M ceoftoU- wfifc oefl Ur*v eeacfeSMMU Itftw 0*** *fu> % alack coaslun. Wt iMtofi <VrftK>BtUoc vttb tor epajfaramMi am Jrffca* Z+itt fcUek lU feefoas Qe* Ut*a eaaltw*te ieAon tad a*w1 c&tQ 4o ui p'amsi' uUra Vtfr toa uul aoatoa< r*tA Mtoe* AidwtAjla ABtf pifiaes. URon el hit mait\ lob* L*n* Wat* **it twtflota. wu bdectf Uit ten buiIob' arete Mm# * OMC fr *wv>o4 injection, !>{>-DJfC of poeUBoaf*. Dt-Z>fc<J < typboJtf,. s-swo*. SCHEPER? BT AL TaszX X--Puim**try BffecU of Rare Bank Fluorides Inhalation Method? Animals Died Spontaneously delect Pig*. Sdrtkil, no. Wk, Cm* ol peatS' ZS& * Otom PuMMosrv Sewifos J, JJ. s rBeUQObl* Zartj &8>m cm *4*- ti *oj*Uoe W<& WUM ptfBICOC*' (toe e n TBatireofllB UMvr o?sbm w*ck iU' 1*4, Si, so Beurrt (f) veouUoa Geometric et A6t.91, .n ,w B9 & >Beiiino0la ft JP*flumoofa trtkv) Ufttit |pt(ftoMU' (Job VifiOb* W*Ck Uob wflb toe*! eoseoU- a'EoV CeueaUta tea*? bi*c!t %aotoeUU j**tons iu. * V'ets^w* Votorelippus >ua* with ssarW p!^Bauctoa MKlacBttMd b)Mk M X no ZbauboM* UnkffS 9>CMAUttoB ia.n,a? ue PBTOftOUi* Wti eosMOto setters eteim U*te p* B>eotUas vftfc eoo/es- floo % iso ZWwftMJ* Waek ptfCBast* ttoe w(to tfUereta foei ta4 eoMWtoe aomenon, i. e., that for an inhalation study of such extreme duration the survival rate of the guinea pigs was relatively high. The gross observations (Table 4) re vealed an ever-increasing pleural pigmentatsoo. Pale gray diffuse pigmentation was already present in the anterior portions ol the lungs at two months. During the suc ceeding two years the gray shade gradually deepened to black and slowly spread to the lateral and posterior pleura} surfaces, FinaHy the anterior aspects exhibited a black geometric pattern or heavy diffuse black dust pigmeotatiott, with a diffuse dark gray dust pigmentation of slightly lower tnutnsky in other portions of the lungs. No lesions of comparable kind occurred in any other organ. The chemical analysis of the lungs at the same Vising periods is also of interest (Fig,). Determinations of the ash derived from the desiccated lung tissue and of the silica and rare earth content of the ash, expressed as Thus, during this kagthy exposure, 25 guinea pigs died of mtercorrem causes. The remaining 50 animals were killed in groups of three, every two months, for the first two years and at more widely separated intervals during the last year, i. e., at three-month aad, finally, six-month intervals. In the majority of instances the deaths percentages, are plotted against the duration of exposure. It may be noted that there was no increase o! silica content of tl lung ash over a period of three years, as could be expected, as there was no extraneous source of silica in the dust chamber So winch the animals were confined. No significant in crement in the lung ash could be observed appeared to be due to pneumonia (Table 3), but an episode of apparent scorbutic fa talities appeared toward the end of the first year. Grouped in half-yearly casualty rates, a histogram with the following percentage .Table 4,*--Pulmonary Bffetit pf Rare Earth Fluoride* Inhalation Experiment: AswraH Kitted for SJisiological *rv3 Chemical Stody ,v:::,.i.f;;::v,','T.v.v....li^i^xasrTTrr:11 ;;:!' .i:^=gj'.'T.v.v;;,;ni ,v,y- peaks seems to emerge from this study, tkaih* 5 XI 2 * * Months 0 12 IS 24 S3 This suggests a slight crescendo terminal mortality trend. There may be no patho logical significance to this phenomenon, as it must be recalled that after three years in & dust chamber the effect of norma) aging processes would begin to influence the rate of death an such a group. Indeed, this rec ord would indicate perhaps the opposite phe294 OcE&ea 6mpl!D* Hfl, Ttoe So. Wk. a is.u 8 jSl,tifsc.lB., *i*a, w. <t. a, i 8T.fitf.4D, W.? ir tfi KS (3 40Q 75 ST i9n* m Vtfj m Otmj Puhoeoarjr BeUe &t*bt rr Wcwi*U, tetrfer asterto/i? Bark *t\r WroeauDoa ** tertotlj, bgfet r7 dtr*&crv Hater bJsek ditto# vifmtalttioo aaearlorir. drtr eta? efetwteft: mail fvc) ecuaol0oaa at liutk pisiptai Co^rfmt besvy 4&ttt tivj Ulfcrb )(* wpfKB5W>"*3 jreonwlrfe putter oceasu&*> Uu- e*s* black toeaJ *aflaJaUoc* EFFECTS OF RARE EARTHS ON ANIMAL LUNGS Graph showing the progressive retention of inhaled rare earth compounds in guinea pig lungs over a period o! three years. which could not be accounted for by age changes. There was, however, a progressive *ccoTft\datkjn o$ rase earth compounds m the lung tissue, which matched the progressive pigmentation of these organs, SUMMARY Two blends of rare earths in which the oxide and fluoride ratios were reversed were introduced into guinea pigs by intratracheal injection. conclusion The precise nature of the pulmonary tissue response to the rare earth dusts, introduced into this series of 93 guinea pigs, becomes Apparent only when the histological fea tures are analysed.^ The gross observations indicate, however, that these two blends of rare earths with carbon and potassium sul* fete act as relatively inert substances. The progressive accumulation of the earths could have been suggested from the steady- increase in pigment in the lungs but was finally con firmed by chemical analysis. That the pres ence of this foreign mattei, with Its high atomic density, would cast radiographic shadows was adequately confirmed by other experiments to be reported on a subsequent occasion. t References 1 and 2. An inhalation study with the mixture hav ing a high rare earth fluoride content is also described. The earths are progressively retained in the lung tissues. Apart from evident deposition of the earths in the lung tissue, no gross patho logical changes could be observed in the experimental animals indicating any form of pneutnoconiotic fibrtfct*. REFERENCES 1, Schemers, <*. W. K,: Biological Action ct Rare Earths: J, Experimental Pulmonary Kislopathology Proceed by a Blend Having a Rela tively High Oxide Content, A. M. A. Arch. Jndust Health Sii20lW, 1955. 2. Schepers,* G. W, H,; Biological Action of Rare Earths: II. Experimental Pulrootary RtsM* pathology Prorfcced by a Blend Having a Rela tively High Fteoride Content, A. M. A. Arch, frsdust. Health :<t:306-J16, J9SS. 295 f. Tts Eapcrfateetel Hittpetfcteey frerfucce by a Stead e fsttvly Hiflb Oidtic Cestmr G. W. H.SCHEfEtt, M.O., 0S^, Sattmac Lake, N. Y. Around the air passages there were variable degrees of cellular infiltration (Fig. 15). The alyeolar walls appeared prominently The rationale and method of this esrperi- thickened, owing to remarkable distention iweni have already bees .clarified.* Despite and engorgement of the capillaries. There natze imtiaif losses <4 animals ffom presms'' was,* however, no tendency to intra-alveolar "v ably cbemfcs% induced pneumonia and later. exudation or erythrocyte leakage. faftUtiss tail totercurrent causes, a sufS- Among tbeat distended capillaries there ciently representative series o*-gui?xea pigs were numerous swollen septal cells and a - survived to render posrible a histologkir fair number of eosinophiles, These were of explanation far the pigmented artas found two types, viz., mononuclear and polymor in the Jungs* The effects of the rare earth phonuclear. None of the latter were present blend which had the high oxide content can in the alveolar spaces. The macrophages be men property evaluated also by contrast' i showed instead a marked tendency to acido ; ing *thg microscopic appearance with those philic staining of their cytoplasm, and they found in the experiment-with the high fluo were inclined to be applied to the walls of ride biend * >t the alveoli, and some could be secs to have \ . JWLKQNABy SttpOPATBpLOGY penetrated Into these walls. The mononuclear addophiies, therefore, dearly represented Within s month from the time of the sec- these macrophages after they had found their . and injection of this dust, a distinctive histo:lcgi^I^sttew::d lesions was found in those way into the interstices between septal cells ! animals`that survived*,thp immediate toxic and capillaries of the alveolar waBs. : ` * . 'S'-.*' '. A year after the introduction of iiw dust, some of the initial tissue responses had been ; 'Fhe?e occurred,, fifst, a tendency to focal. completely reversed. The capillary engorge I aggregation of the pigment.^ankles' within, ment, for instance, bad given place to an k atrfcphic alveoli su(rOtmding;or adjacent to1 ischemic state.* Gills were now relatively -> terinftBtl bronchi end fetoa&iolcs/ For the ' inconspicuous within the alveolar walls u greater'pirt such pigment was intracellular,, .except where the alveoli abut onto one an* being confcdned within large .giant cells.. 'ether. Here macrophages, polymorphonu Some '.oi the jartidts also beenrred within' clear -eosinophils, and fibrocytes wore con < the'alvcoiar walls (Fig. lA).k / . gregated. Collagen was found to be sparsely The corresponding bronchi or bronchioles' hud down with* the afaeotar walls, and some showed fairly extensive epithelial swelling, of th? latter tended to be ruptured. '.ticeratsofi, and desquamation, the majority of the fumtna feeing filled with cellular debris. Some of the peribronchial and subpleura] macrophage accumulations persisted. For Recorded for pubSkaiion July II, 19SS, the most part they had disappeared, but when Director, The Saranac Laboratory. present the macrophages were stilt markedly 296 i A Fig. 1/--Anion of rare earth oxides on the gwne* pi* Jung--intratracheal ia|tionr one month. A, focus of iwra-alveolar aceoraoUtion of pigmeM; most of the dust has been engwif by macrophages, and scene is being transported to perira&colar lymphatic*. Br area of penfronchiolar pneumonitis, with fod of cellular proliferation; bronchtolar epithelial catarrh and swelling of alveolar walls are present. Fig. 2.--Focal depositron of rare earths--result after one year. A, massive parsbroochial pigmentation, with minimal ckatriodon. B, minor psrabroochbiar earth deposit. a fair amount of whkh Is contained within macrophages. SCHEPBXS eosinophilic and tended to form giant cells through confidence. In relation to the sites of dust deposition, no sigusfic&ht cellular reaction could be found. Host of these de posits were parabrooch&l, snd in some i&sl&rtces the corresponding bronchus was surrounded by oar tissue (Fvg. 2A and B). The parenchymal lymph nodes showed some central "endothelial cell prohferattosv, with perilymphatic fibrosis. The hilar lymph nodes displayed considerable medullary and follicular endothelial cell hyperplasia, pig ment deposition, irregular fibrosis, and marked eosinophilta. The main histopathoiogical trend beyond the first year devolved on progressive hyper plasia or cellular infiltration of the parenchy mal lymph nodes and hilar nodes. At the end o( 540 daysthese structures had acquired an almost granulomatous character (Fig3A). The lymphocytes had been progres sively displaced or even replaced by large endotheliokj ceils, fibrocytes, and occasional pigmented cells. Collagen was found to have been laid down in sparse irregular bundles, but the nodes were fairly well vascularized and remained well demarcated from the sur rounding lung tissue. Not only did the main lymph nodes of die parenchyma show this incipient granulomatosis, but comparable changes occurred at a multiplicity oi pulmo nary sites, generally parabronehia! or para vascular in distribution. The hilar lymph nodes Uktwise showed marked medullary infiltration by means of solid phalanxes of partially pigmented, faintly acidophilic macrophages. The amount of pigment now present in the nodes was quite considerable, but there was no significant aceurmsUtion here of fibrocytes nor was there any depo sition of collagen (Fig. 35). COWtfSNT Several issues of significance are raised by the results derived from this analysis. Points Peg. 1--fW&5( reaction to rnwatratbeafi? introduced rare earths--ruH at 570 days. A, dominantly cellular paravascular pulmonary granuloma without conspicuous pigment content 5, hilar lymph node showing focal aggregation of the rare earth dust without associated reaction to its presence. ,1'? fh''*1' 'r-\y,S l'a; :i /w* 'UK V 1.1>4 298 BIOLOGICAL ACTION OF RARE BARTH OXIDES of possible industrial medical significance cootera the conspicuous absence of fibrosis oi aoy material degree and the focal aggre gation of pigment in atelectatic alveoli. The lack of fibrous reaction immediately directs attention once more to the funda mental contrast between the malignant effects of quartz dust at one end of the scale and the benignity of other dusts. There is a growing body of medical opinion which re gards all dust as harmful, and few authorities will be found who would be prepared to deny this axiom provided that no limit is set for the range of dust levels to which It applies. But, dose for dose, it is dear that dusts vary markedly in respect of their fibrogemdty, and the rare earth blend under review must be classified as inert except for its capacity to provoke some chemical pneu monitis. There was too little potassium sul fate in this blend (3?&) to have played a significant role as an inhibitor of fibrosis but the carbon (31 %) may have reduced any intrinsic pathogenicity which the earths may possess. It is in theory possible also that the ratio of rare earth fluorides to oxides would nullify any sclerosing influence of cither component. Such leads naturally need to be followed up. The injurious action of any dust may also express itself by way of its effects on the bronchi,and alveolar membranes even when no fibrogenic stimulus goes forth from it. However, in this series of rare earth expo sures neither bronchitis nor bronchiolitis persisted after the initial irritation caused by the introduction of the du suspension, and no terminal emphysema could be dem onstrated. The prolonged focal persistence of tare earth deposits may furnish a clue as to the reasons for radiographic mottled shadows whkh may be demonstrated in men who hsve been industrially exposed to these sub stances under conditions facilitating the in. halation of dust. Discovery of such shadows in plant personnel should dearly be inter preted with some caution; they would prob ably correctly signify a benign underlying condition comparable to barifosis or argy rosis rather than a disease associated with fibrosis or asy other progressive process. The fortgoiag cfesfoctiou requires one specific exception. The delayed effects of the rare earth dust appear to include a propen sity toward granulomatosis of a kind some what reminiscent of that already well popu larized as a chronic lesion associated with cAe inhalation of cc/tam bcryUfttn com pounds. Apart from the intrinsic significance of this lesion, the presence of such granulo mata could possibly cast additional roentgcnographie shadows. It is of significance to note that the granulomata first appeared when the rare earth components were bring progressively with drawn from the pulmonary tissue. Inciden tally, no study was made at the time as to whether beryllium compounds were or were not present in the rare earth blend. Attention should also be drawn to the fact that the granulomata developed within lymph nodes by a process of substitution for the lymphoid tissue. This process is somewhat cootrary to the apparent sequence of events in beryllium disease where granuloma forma tion may oftener than not commence in alve olar walls or at the angles between separate alveoli while lymphoid tissue mostly escapes early involvement. A further point of con trast concerns the marked lack of the fibrogenic action in relation to these granulomata is the rare earth ensure. The marked eosinophilic reaction is appar ently a distinctive phenomenon in this case. Not only did eosinophllcs occur early and persist to the end of the experiment, but they varied from polymorphonuclear cells to monocytes and could be found in the lung parenchyma as well as the hilar lymph nodes. The presence of ebsmophiJia has recently been reported in connection with the experi mental exposure of guinea pigs to cobalt metal,9 It also an early manifestation In the reaetkm to quartz dust,* the difference bring tha^ quartz is acutely toxic to the eosinophiles whereas the rare earths do not appear to destroy them. A final point of interest concerns the pro gressive transport of the earths to the hilar 299 SCHEPEftS lymph nodes and the delayed reaction at this site- Byanafegy this occurrence might signify that, given enough subsequent tim^in normal air, industrial personnel who had inhaled the dast and In wbo lungs suggestive Tnttiat? rsdiopadties had become established may anticipate ultimate amelioration of this sign, ft would be of interest to know whether such extrapolation is permissible. SUMMASY ANI CONCLUSIONS When introduced into the lungs of guinea pigs, a blend of rare earths with a high oxide content produced fatal delayed chem ical hyperemia in a third of the animals. In those that survived the introduction of the dust, cellular eosinophilia was a prom inent feature... `'Most oi^he.. dust was trapped within focal atelectatic areas, aa4 no material chronic cellular reaction or fibrosis occurred in relation to these deposits. Isolated cellular vascular granulomata were found after a year. Most of the pigment seemed gradually to be transported to the hilar lymph nodes but eansed no significant reaction there. REFERENCES J. Stfhepers, G. W. H.; Ddahant, A. B,, asd Rediin, A. }.: An Experimental Study of the Effects of Rare Earths on Animal Lungs. A. M. A. Arch. Indus*. Health 15:297-300, W& 2. Stfcepers. G. W. H-: The Biological Action of Rare Earths: II. The Experimental Polaooary HistopaShology Produced by a Blend Having a Relatively High Fluoride Contest, A. M A. Arch. Indust. Health 15:306-316, 1955. 3. Scbepers, G, W. H.: The Biological Actios of Particulate Cobalt Metal: Studies os Experi mental Pulmonary Ktstopadtology, A. U. A. Arch. Indust Health 15:127-133. 1955. 4. Scbepers, G. W. H.: Cytobiological Mani festation* of the Surface Properties of Quartz A. M, A. Arch. Indurt. Health 15:266-275. 1955. 300 lL Tk* ExpetswaWl ?tnoflary HoyIaq e ftetetaeh Hijfj FIsorJ* Crtfe*t hi e 8la4 <k W. H. SCHItm, ^D. P3c,Sflreee UU, N, Y. Although the blend of rare earths with a relatively' high fluoride content was not significantly more toxic when introduced mtratracbe&Iiy than was the blend with the higher oxide ratio, to judge by the mortality trends,* the histological lesions provoked differed considerably * In the present account the pulmonary lesions produced by the high fluoride rare earths, both on intratracheal InjdfctiOn and alter a prolonged period of inhalation, will be described. These experi ments have already been outlined.1 PULMONARY HSSTO*A?eOL IKDUCtT by INTRATRACHEAL EXPERIMENT The immediate pulmonary tissue response to the intratracheal injection of 100 mg. of this dust manifested itself as a marked paren chymal hyperemia and as bronchitis and bronchiolitis. This acute reaction was still present at the encTof the- first month after the second injec tion and was seen to consist of massive dis tention of capillaries, some being so engorged as to completely occlude the alveolar spaces,. There was, however, no material tendency to leakage'of serum or blood cells from these enlarged blood sacs. The bronchitis and endobronchitis per sisted in a subacute form at the end of the first month There was considerable tpitbeJial necrosis and desquamation, and plugs or debris filled the lumina of some of the air passages. More spectacular was the promi nence of peribronchial cellular infiltrates, Kecorderf for publication July 11, 1955. Director, The Sar*c Laboratory. comprised mainly of lymphocytes and mac rophages. Eosinophiles were not prevalent. Dilated blood vessels were found lying among these cellular deposits. The bronchial muscular layer had become hypertrophied even at this early stage, and the alveolar daces tended to be dilated. This suggests that a state of bronchial spasm and obstruction to |dr Bow had prevailed in the preceding weeks. Regional peripheral emphysema also was in evidence (Fig* M). Around the smaller-Mood vessels there were marked lymphoid concentrations, and the parenchymal lymph nodes themselves showed some marginal proliferation. Scattered pigment deposits were present The sites of election for these were in close proximity to. bronchioles, more frequently in relation to those that had become partially plugged by mucus and cellular detritus. Most of this pigment was extracellular, though some was present in macrophages and some had entered the alveolar walls. Koniophores were, however, relatively scarce within the alveoli. - The enlarged hilar lymph nodes showed marked medullary endotHelial-cell hyper- plasia ahd'dafiitTation by naanspf acidophilic pigment-bearing macrophages (Fig. IF). The leniency to capifiafy distention per sisted regionally even after the expiration of a; full year. This phenomenon was most marked whpc there were conspicuous dust deposits, Aj such regions scene cellular pro liferation m the walls of the containing alve oli also ctxad be found. More generally the alveolar waits had al ready become attenuated, relatively acellular and avascular, and contained very little pig ment or koniophores. There was. however, | 301 ')>*);WmJ' SCttSPSW ). * oi O ;y< fX3 Fis. 1.--Early and delayed reactions to iofratracheally introduced rare earths--100 mg. dose; pgs. A, limp: marked hyperemia with bronchiolitis (one month), fl, hUar lyms* node; fconsopfcwe inrmration in the medulla (one month), C, massive parabrorxhiaj deposits' dust trapped within atrophic alveoli around a partly regenerated bronchus (17 months) D, hiiar lymph node; focal accumulation of pigment without regional fifoem or vascular flamae* (17 months), * 302 V XL BIOLOGICAL ACTION OF HARE BARTH FLVORIDF.S . oo ^trophic vesicular emphysema .'through epithelial ceils of bronchi and - bronchioles njpture'bf adjacent walls, but in some areas contained' black granules. This observation the alveoli remained relatively distended. constitutes a most unusual phenomenon m The cellular infiltration around blood ves dust .experiments and seems to signify an sels had receded, leaving an insignificant undue avidity of tissue cells for this dust. residuum of cellular collars encircling smaller A variable degree of cellular proliferation vessfeau .The bronchioles arid alveolar ducts or accumulation occurred within the alveolar were ujdined to remain distended. There was walls and consisted almost wholly of mac some trend toward crypt formation suid epi- rophages with occasional eosinophilcs and theiiaiization of proximal alveolar walls. The plasma ceils. Many of the alveolar walls ap lymph nodes showed marked medullary mac peared completely normal; yet many others rophage infiltration but no distinct fibrosis. showed marked capillary engorgement. Yet ' Healing proceeded very slowly, and by the others seemed to have become dcvascular- enfr$l|570 gays regional hyperemia, cellular: ized. The latter appearance could be related infiltration, bronchitis or bronchiolitis, and to the fact that many of the smaller arteriole* atrophic emphysema could still be found even were closely ensheathed within dense collars though`very;few dust particles remained inv- of macrophages and plasma celts which en the. parenchyma! pulmonary tissues. All i croached iUpcm'.ihc vascular lumina. such master appeared to be withm the occa-^f Nodeosive'txiSkd toward regional aggre skffial kbmophores which were present. At* gation of.the pigment deposits or the cellular * isolatal sites where the dust had been heavily'' accumulations could be discerned at such an 'deposited around bronchioles, the lack of early stage. The parenchymal lymph nodes fibrous reaction could be well seen (Fig, 1C). showed no proliferative response, but the The affected bronchioles showed some dis hilar lymph nodes were found to be swollen tortion but had become partially healed. The through moderate medullary hyperemia and hilar lymph nodes also showed marked macrophage infiltration. This reaction was medullary infiltration by acidophilic macro out of proportion to the limited amount of phages and some fibrocytes, but there were pigment concentrated here. no materia! collagen changes despite heavy The bronchi and bronchioles tended to be focal deposits of.rare earths <Fig. ID).' a little distended, but the epithelial surfaces were norma! except for a tendency to absorb niSfCiUWiCAL CHANGES RESULTING FROM pigment. * INHALATION EXPERIMENT At four months from the onset of the in When the dust was introduced more slowly halation experiment, the tissues revealed a and caused--to accumulate progressively decisive change. Now numerous areas of in within the pulmonary tissues by means of tense cellular accumulation could be found the inhalation experiment, certain essential m subpleural, perivascular, and peribronchi- differences in' the tissue reaction could be oiaror parateondifola;'locations. At some observed. rites tm: swollen alveolar walls had become Tiie particles were readily phagocytosed virtually confluent (Fig. 22?). The main com by alveolar macrophages and evidently as ponents of these areas appeared to be mac- rapidly transferred to the alveolar wails. In- rophagps and plasma cells, but some lympho deed^t the end of the second month as many cytes and polymorphonuclear leucocytes were dust-filled koniophores could be seen within also tojbe seen, and vascular capillaries sur the alveolar walls or at the interstices where vived within these consolidated areas. No different alveoli meet as could be demon eosinophiles were present. strated within the alveolar spaces or within For tiie most part the capillaries were en free-lying koniophores (Fig, 2A). Pigment gorged^ and at isolated points the distended could be identified within the cytoplasm capillaries had ruptured, with extravasation of the alveolar septa) cells, and even the of erythrocytes into the alveoli. t m V SCTIRPEftS Fig. 2.-~Eaeiy pulmonary response to inhaled rare earths--guinea pigs. A, alveolar walls showing pigment-filled macrophages applied lo and penetrating the alveolar walls (two months). B, dvSose awl local tblas preUkmh*. Vn jmlmotiV'y parenchyma Uour months). C. pccieaseuJar accumulation of intracellular pigment (12 tnomhs). D, stibpleurai focus of cellular infiltration (12 montfss). 304 V BIOLOGICAL ACTION OF RARE BARTH FLUORIDES .An interesting feature regarding die dust pigment concerned Its marked predilec tion for incorporation within enormous koniophores, which showed distinct pseudopodia by means of which they adhered to adjacent alveolar wails. Distended though these koni* ophores were, nevertheless they managed to insinuate themselves into the interstices of the alveolar walls, and many could be ob served partly imbedded within the alveolar septa and partly protruding from them. The lymphoid tissue in the lung also showed some marginal proliferation, with ceils infiltrating into the adjacent alveolar septa. At this early stage the hilar lymph nodes did not show any marked change be yond that already noted. By the end of the first year the foregoing pattern of reaction to the inhaled dust had become well established, and certain addi tional features had been added. The progressive accumulation of particles within the alveolar spares and around smaller blood vessels was now much more apparent. This pigment occurred as large masses in relation to which macrophages were not al ways detectable, though it may be presumed that some cytoplasmic elements were cement ing the particles together (Fig. 2C). Cellular masses were .now more prevalent in the subpleural zones, and within the cen ters of some of these areas some necrotic changes were noted. Frequently these cellu lar tones were also markedly hyperemic, and hemorrhages occurred into and around these regions (Fig. 2D). Quite an advanced degree of atrophic vesicular and hypertrophic focal to bullous emphysema had supervened at a multiplicity of sites toward the end of the first year. Some of the former types of emphysema could have been due to degenerative changes in the alveolar membranes, but the latter variety was almost certainly related to asso ciated changes in the bronchi. , Chronic bronchitis and bronchiolitis had become well established. The essential lesions comprised epithelial necrosis and desquama tion with attempted papillary regeneration, but a mucosal reaction was not a prominent feature. The air passage distention seen at earlier stages now constituted a distinct bronchiolectasia, and a certain measure of crypt formation was present. Desquamated detritus occupied some bronchi. Toward the end of the first year the in flammatory type of reaction had almost com pletely subsided. The lessened alveolar wall hyperemia even gave way to apparent ische mia. At isolated foci there still was some evidence of cellular infiltration, and areas of almost complete lobular consolidation by macrophages could be found. No fibrosis was observed m these areas. This type of reac tion did not increase as the experiment pro ceeded, and the presence of these reactive zones could have represented residua of earlier more extensive inflammatory reac tions. Throughout the subsequent two years of this inhalation experiment, the rare earth dust slowly accumulated in the lung tissue. The maximal deposition occurred subpleurally and as paravascular and parabrooebiat condensations. The pigment was found not only in macrophages applied to the alveolar walk in these regions but more particularly accumulated in lymph spaces and nodes in the hang. The hilar lymph nodes, however, showed no significant progressive infiltration during the second and third years, beyond the stage, already reached by the end of the first year; nor was there any focal cellular or fibrous reaction to the presence of these pigment deposits. The emphysema which had become evi dent at a.quite early stage of the experiment evolved ipto a characteristic and progressive disorder |during the second and the third year. The atrophic vesicular phase receded in significance once tee inflammatory stage had subsided. In its place the hypertrophic focal variety evolved into a multifocal bullous disease. This change was most marked at the lung periphery and in the apices and bases. Many ofHhe bullae became so large that they comprcsled adjacent alveoli. Though their walls became extremely attenuated, they did not readily rupture. In some instances epitee- * 30S *4 4 SCHEPBRS Fig. 3.---Genesis of focal hypertrophic emphyseaa--inhalation of rare earth*!: guinea pigs. A, bronchiole with distended alveolar ducts (12 tnoaths), B, duster of distended alveolar ducts aroand a blood vessel (16 months). C, alveolar ducts dilated at the expense of adjacent alveoli which they compress (24 months), D, perifoal emphysema through deposition of pigment in relation to blood vessel (30 months). 30b BIOLOGICAL ACTION OF RARE EARTH FLUORIDES Fig. 4,--Genesis of focal hypertrophic emphysema--iohatation of rare -nhs: guinea pigs. A, incipient distention of alveolar ducts wSfi normal alweoti w*d.$roiv9uo1ei (two months). B, sphincteric narrowing at point of juncture >weea alveolar ducts and bronchioles (S$ months). C, distention of alveolar ducts and bronchioles with, some mural rupturing (36 months). D, distention of peribronchial Wood vessels a&<i sphincteric nawowing? at points of bifurcation oi bronchioles (36 months). , SCHSPBUS lialixation <A these bullae proceeded outward from the proximal alveolar duct* and bron chioles, many of these alveolar ducts them selves having become markedly <tistended kept of any possible associated cor pulmonale. Distention of fee bronchial vessels vras demonstrable at fee end ot fee three years of exposure (Fig, 4Z>) and may possibly have and resembling bullae, Wltere the bullous spaces invaded areas of`cellular proliferation, a very characteristic honeycomb effect was produced- The evolution of a characteristic cluster of bullae has been traced in Figure 3. As is evident, the distention of alveolar ducts commwKtd at an early stage and preceded en largement of the alveoli, which became plowed open from the proximal to the distal portions. The distending alveoli then became clustered about the parenchymal vascular system and by compressing and displacing intervening alveoU eventually abutted di rectly on the vessels. At this stage, reached toward fee end of the second year, the emphy sema cannot yet be classified as the penfocal variety. However, during the final year of die experiment, fee intrapulmonary pig ment increased markedly, and by infiltration around and in relation to the blood vessels, the characteristic grouping of bullae round a focus of pigment (Fig. 3D) is seen. The walls of these distended spaces ap peared to be very thin but apparently did not rupture readily, though some interrupted septa could be seen toward the end of the third year (Fig. AC), Cuboids! eyafedium lined these spaces partially, and it is dear some relation to fee evolution of fee restricted pulmonary circulation and fee possible estab lishment of a collateral circulation. The respiratory passages revealed a series of interesting changes. Fusiform distention of the bronchioles and alveolar ducts was demonstrable within two months from the start of the experiment, shortly after fee acute bronchitis had commenced to change to a more chronic phase (Fig. AA). By the cod of the first year chronic inflammation had be come associated with the development of prominent epithelial rugae and sphincteric contractions of the lumen at points of bifurca tion of the bronchial tree, Isolated saccula tion* of fee wails of bronchioles and cf fee alveolar ducts were also present (Fig. 45). The scars of earlier periods of more acute inflammation could frequently be seen to dis tort bronchial walls at points where fee tnus* calaris was Interrupted (Fig. Sj4 ), That even at this delayed stage (18 months) the bron chial mucosa was still actively participating an the retention of fee rare earth dust is evi dent from Figure $B. The masses of pigment demonstrated-ate contained within koniophores. It is not dear, of course, whether the pigment was being extruded by this route, after haviog been trapped within the alveoli that these cells were remnants of normal and transported by the lymphatics to fee constituent* of the Sung, having been derived bronchi, or whether fee pigment represented from the alveolar ducts which had changed into these bullae. Considerable pulmonary vascular medial new dust recently absorbed diftetiy by the bronchial epithelium. While some of fee alveolar ducts had be myQhypertrophy, apparently associated with come grossly dilated, others ol these duct* this emphysema, had supervened toward the end of the third year of exposure. Capillary circulation through the walls of fee alveoli appeared unimpaired for a prolonged period persisted among the bullae as relatively atrophic structures surrounded by pigmentladen alls (Fig SC). Toward the end of the third year of exposure, the focal deposition of after the initial phase of engorgement. To ward the latter months of the third year of the inhalation experiment, alveolar wall ischemia became partially evident, and it is, of course, possible that these regional changes may be related to the muscular hypertrophy in the blood vessels. Unfortunately no record was fee pigment in relation to the sphincteric narrowings, which lie proximal to fee dis tended alveolar ducts, had become dearly demonstrable (Fig. 5D). These regional nar rowings were not necessarily associated only with bronchi which were the seal of active chrome inflammatory reaction. 308 BIOLOGICAL ACTIOS OF BARB BARTH FLUORIDES Fig, 5.--Bronchial changes induced by rare earths--inhalation method: guinea pigs, A. peribroflcnial infiltration and minimal associated distortion of walls (18 months). B, pigment-laden cells infiltrating around distended blood vessel. Into mucosa, and between bronchial epithelial cells (18 months), C, distended alveolar ducts resembling alveoli but partly lined by cuboidal epitheKum; one atrophic duct surrounded by pigment-containing cells (18 months), D, deposit) of rare earth particles in the adventitia of a bronchiole opposite constricted annular zone of transition to alveolar duct (30 months). * f'X* SCHEPERS comment the rare earth blend which were capable of The wsulU *3? this experiment with rare provoking tlit mild degree of chronic inflam earths in which the fluoride salts predomi matory reaction would possibly act chemically nated raise numerous issues Seyond those on the pulmonary system of innervation and specifically concerned with the toxicology ol particularly at the sensitive synaptic junc rare earths or of fluorides. tions. The latter are present m the lung as The dominant pathological effects provoiced are the bronchial changes and the emphysema. The explanation of this tmphystma phe nomenon appears to reside in the sequence of changes affecting the bronchioles. Indeed, as the bullae on final analysis really are disten tions of the alveolar ducts, the disease process truly remains limited to the respiratory pas ortbosympatbetie relay stations; assuming for the moment that the parasympathetic fibers of the vagus are not as readily affected by the chemical agents, as they have no syn aptic relays such as are known to exist for the oribosympathetic nerve fibers, the possi bility of a focal inversion of autonomic bal ance would arise. This would then be an instance of a chemically induced neurogenic type of focal emphysema. sages. Which came first? The widening of the alveolar ducts and terminal brorechw^es com menced as early as the second month of the experiment, before there was any possibility of mechanical (actors as a cause either in the form of obstruction or distortion through local pigment deposition or fibrosis. On the othcT hand, the regional valve-like or sphiocteric appearances cannot be ignored as pos sible mechanisms in the final phases of the genesis of the emphysema. Morphologically speaking, these sphincters do not appear narrow enough effectively to block the r flow past them, and any obstruction rigid enough to achieve the latter result would It is but ooe step from this experiment to Heppleston's1 concept of focal emphysema in coal workers. Coal has such a diversity of substances within it* composition that it would cot be surprising to learn that the essential components in the high fluoride rare earth Mend which produced focal emphysema experimentally are present also in coal and thus would perhaps be the causative agents of coal miners' emphysema, it is perhaps not even necessary to have the identical chemical agents. I have recently shown * that several unrelated heavy metals appear capable of producing comparable lesions. more likely lead to regional atelectasis. !t is Why then has focal emphysema not previ possible that the prominent rugae near these ously been experimentally induced by coal narrowings may act as selective check valves, dust? Species specificity may partly account which are (oiced againsi the strictored seg for the phenomenon, Thus, while coal may ment of the lumen on expiration but move produce emphysema in man, it will not neces out of the way on inspiration. Some of the sarily do so in animals. By the same token, flaps demonstrated. m this series could pos one cannot extrapolate the results obtained sibly act is such a'maaoer, but others would by theipresent experiment directly to man. have the diametrically opposite effect, to* Not until emphysema does become an indusjudge tly their anatomical disposition in rela- . riially significant disease in workers exposed tion to the stricture^ aone. -The more,likely to rare earth fluoride dusts, would the present explanation seems entirely speculative aod.H findings od guinea pigs become applicable as an explanation for the human disease. based on the demonstrated deposition of thi * * rare earth particles'in juxtaposition to the It is possible also that experiments on coal, sites of the autonomic ganglia and nerves via. carbon, or graphite have not always been which the motor tonus, peristaltic waves, and. carried through for a sufficiently long periodother rhythmical contractions of the 'fironchj Emphysema, became clearly established as a and bronchioles are regulated. It may be pre- . dominant disease in the present experiment sumed that the same chemical cofjiponents ol ..'References 4 and 5. 330 ' '' *'C'*'7V ` '' "t .BIOLOGICAL ACTION OF RARE EARTH FLUORIDES attei a period of prolonged expoc. sure. Even in The Saranac Laboratory in- haiatkra studies have no* always been pro longed for three years. Perhaps repetition of the si experiments cr*e* swh a prolonged period would bring about the desired result. It Is possible too that no significant changes are produced in the hilar lymph nodes, be cause the particles are not necessarily perma nently retained here, bring redistributed to tiie rest of the reticuloendothelial system as fast as they reach the hilar nodes. A further significant discovery which has relevance to the problem of coal miners' emphysema concerns the observation that the focal distention of the alveolar ducts preceded sumuaby 1. When introduced by intratracheal in jection, a blend of rare earth compounds the massive deposition of the dust in the lung. It has generally been assumed that in coal miners the anthxacosis precedes the emphy sema. A study of autopries on coal miners who died from accidents in the early part of their career might reveal significant relevant data. dominantly composed of fluorides provokes an acute transient chemical pneumonitis, subacute bronchitis and bronchiolitis, and residual deposits in relation to which no reaction occurs. 2. The dominant bistopathological changes which result progressively from the pro It should be pointed out too that in this blend of rare earths there was no silica. The opinion is widespread that quartz is the cru cial factor m the generis of disability of coal miners. Evidence seems to be at hand that the causative agent in coal need not necessarily be longed inhalation of the rare earth high fluoride dust comprise focal hypertrophic emphysema, regional bronchioiar structuring, and subacute chemical bronchitis, figment is fiscally retained but provokes no fibrosis or granulomatosis. the quartz but may be some other ingredient. The evident avidity of the komopbores for the rare earth blend in this experiment con trasts with the minimal degree of hilar node 3. The results furnish clues concerning the mechanism of coal miners* emphysema. REFERENCES involvement in the Inhalation experiment. The presence of dust-laden cells in the bron chial mucosa and epithelium furnished a hint that the route of elimination of the dust was partly via the bronchial mucosa, so that the hilar lymph nodes were bypassed. The capac ity of the koniophores to gorge themselves with the rare earth particles until they had attained up to 10 times their normal dimen sions may have led to the implication that such Juggernauts could not be transported all the way to the hilar nodes, dying on the way and ultimately accumulating locally in the lungs. It is also possible that such en gorged cells may have blocked the finer lym phatic passages after they had ceased to be able to change their shape by ameboid action. I. Sehepers, G. W. H.; Delaham, A. B.f and EedEn, A. J,: Ac Experimental Study of the Effects of Rate Earths on Animal Lungs, A. U. A. Arch. Indust. Health 12:297-300, 1955- Z Schepers, G. W. H.: Biological Action of Rare Earths: L Hie Experimental Pulmonary HistopaihoSogy Produced by a Blend Having a Relatively High Oxide Content, A. M. A. Arch. Indim. Health 12:301-305, 19S5. 3. Hepplesfon, A, G.: Pathological Anatomy ri Simple Pnewnckotttoris ar Coal Workers, J, Path. & Bact 25:235, 1953. A. Schepers, G. W. H.: Biological Action of Tantalum Oxide: Studies on Experimental Puboo nsry Hlstnpathology, A. M. A. Arch. Indust Health 12:121-123, 1955. 5. Schepcri G. W. H.: Biological Action of Celtic Oxide: Studies oh Experimental Pulmo nary Hbtopathology, A. W. A, Arch. Indus*. Health 12:124-125,1935. 1 322 ^xperimentaiStud^ oftie C*j!$ect6 of ^Da,$c <2^utt on -*$nima$ ^Jbdue e. w. a scHints, m.p,, d.sc. oai T. R CURRAN, W.L, Sotsmc Loke. N. Y. nent substances. In these experiments the mineral, or mixture of minerals, in the form of 9 dust suspension was introduced into animals by the intravenous and by the intra The occurrence of a scries of deaths from pulmonary disease following -exposure to tak tracheal technique. Rabbits, guinea pigs, and rats* were used, but not both techniques were employed for each species. Minerals selected mining in upper New York State caused for their purity were used, and in some in The Saranac Laboratory to inquire experi stances contaminating substances were re mentally into the precise causative agent of moved, or reduced in amount, by sedimenta this form of pneumoconiosis. This series of tion in heavy liquids. ;expcriments,.jn -which one bf us (T. M. D.) participated, ^as conducted at The Saranac Laboratory under the supervision of the late Leroy V. Gardner, M.D., during the period 1937-1941, and the results ate now reposted for the first time. They have lost neither The progressive and essential steps fol lowed in conducting these experiments are summarized in the accompanying Tables. A separate control study with quartz was at* performed, as the effects ol this substance had already been established by previous ex their relevance nor importance, as instances periments at The Saranac Laboratory, and of talc pneumoconiosis recur sporadically, thoseexperiments serveas a controlstaadatd. and a recently resected lung apical lobe from a paper-mill worker, suspected to be suffer ing from tuberculosis, revealed on study by The intravenous method of introducing dust into animals was used in an investigation in whkh the mineral dast, ground until the one of us (O'. *W. H. S.) that talc dust may particles were 3> and smaller in size, was in cause lung disease in the most unexpected of jected into the vein of rabbits and of rats occupations. ... . A study of the dust to, which eight fatal cases* were exposed and of the minerals re covered from their lungs * showed .that the . mineral tak.is but one-of the components of . commerciaf;talc, to which the^.were exposed. Along with sthe talc there occur' in variable proportions' tremotite, anthopbyllite, quartz, serpentine,* and dolomite. The animal ex- ' periments were, therefore, designed to probe the specific effects of each ;of, these compo (Table 1). Both species were used in the studies with talc, soda tremolite, and serpen tine, and rabbits only in experiments with soda-iron tremolite, anthophylhte, and dolo mite. The intratracheal technique was employed in three sets of experiments. In one set (Table 2), the four minerals studied were injected in the form of particles aud less in size, and, in addition, two of the minerals (tremoTite and amhophyllite) were used as a dust composed of particles 20/ and smaller ReconW for publication July II, 195S. in diameter. In the second set (Table 3). Director (Dr. Schepers) arid Associate Director which was conducted with fibrous minerals, (Ur. Durban). The Saranac laboratory. the material was crushed and then separated * 312,.'. r" JsWCrJ 0^ TALC DVST ON ANIMAL T/SSVE T*ats 1^-inirtevewa Injection ErporimonLc 9ith Talc and Auociated MinoraU * *e*u*, .u:'.2>j,v# >.. ,r ` , * .?-# tas or '^fT&vHfpeau&SBAooaOJstfecjtaeMd tnntmJ ,v " i"' (. dMAtiTtetO 9 oqotf ditto f**ft dfloe *U UHo Ut.ttf Ttdft. `' '' :.' '**?? ***$ tWWJ4dtAf oonnootteerrtt dof ddccoo** llaoj}ecttaadd vat I Ac. 4M6td fete a 4om A*f^M *t 04 stf. ffijBrcy*'*:*% MtttM) teju* rwt anttlorun j**** `M VUcfeLAalBota Were BjMi'Untnr.M tDtem*ftf4 te * . . V-*** * or f.te# a*atfl IMhlur. afe _ to s* # otter Weetfoe -*7v Aatoalrf ^ , ,-i- ' ' **,' j" oraieorf*):...'-.,.' Ho. ^.v' fP-i;4 2onK* * . tuda. codorterfta* pndforu*. *9xwnrtHn'tetewb. pfesrof tfefekoUa* ^ _;_r_i__H___ ' ,,/ .*.. fpa38a'{tefe)}../;. ..../ ut AO0_- **> a <T onb'Ub 10* $4 4w"^ca^>asasw>2 SoIoib^..3yj;'./'^'^'L-. im ^ (> t uiktu-.s u f&fioii .' ^WooiferiKfex feffitntei toflJCtM# rteudoatte :/' 'Tnu^^ftofooTtoott mmS tenant* }\ MinoraU *&'***#"* dosi^w^j ad. Um toAtBatrfkr^H^#pc8^EtiSF ta (Oaortia) TW............. ' 'BtO>1 ....................... >' IdSWA.- : " ytrtiao sue.A 860 S tod Ha .' sa&dte* TranSlii {iftt} loaodiees ^?ce *Ti >' --y, *:y<'I*' vr' :.rf:V' Utcasat aMiAba'.rv^^oV:? ^4FHSteti' d oao - rs~>^. -''ri. t-.mr^a-t^-r ittlaetfo* Hazfnt] .. SuirftJ * After Lat AoV lajaetHb, HtU Ho.. U9 . 4 .' *. m . u * u Brooetdalae(aHa aad bm&dkJSa; wdaMidar oad partbroochia) aoUotar prolitoatiMa aad flbtoila; flbtoeE^iar-pk^nl U>rx^ 7%am4(St tnomvban rooMlos aad perbUtost ofiao^flla: parlTWRflUi *M soaftrowUti ina- pboeyUe laflUMHea Lartptan bmoelitolaetaJ* aPd pcrfbriMh(B3 0bn>> BarfomaoHr IsaiU'CUA |)^BU* - *. ---' 'aaoaaim^ < JU t6^#aV /J..W -> - '!* `*' *?/.TaU 1--/n*mrArtf InjetlifM.* ExPfrim ^=if== Dum \Jtt?RWed ol Bn0*MetMU.^ - . * M toui ot <W*t tajaeud u , aav&t doM* <ocb Aettt **> M ni j ; aajwtiou of uaaaffw tad .too' of c&tfcepfaySf [ 0*ed: Oat&M pits. a'"' r T^zffkt t./WUeb AedaoS* 9 SIM: for tM^obco 1, .Sad li roosth* ontr Wi HJecttoD. /' Hirtaa) X v. ,' SartkaJ ( r]<^ -<AJp) PlbM iwortofi, Leoplb. a Aoteab He. J&60 -8 B I^ f. Aou&phr*""> SCHF.PBRS AND DVRKAN Table 4.--hUratrtxhsaJ Iniictien Experiments Mixtures cf Talc Miaerals and Quart* Sou**: to total ttaocBt of deit iojanod m m*. dltistd tow am **nJ deaea (ate* Mo* fu e* atf. or * 6% aupaotiw) S3t*4 ank apart. APfaaaJj Pad: SrIm* plr*. Prtad* at WfefcB anfmrt Wcrr DIM: XSn& i, t, JS, ud j* uostM alWr Uat Islactleo. Uatl MUCBN Tafc................... .. Qvtrtt.................. fV 0mt t* Si TwaeUt*............ Qbbtu.................. Aotb&pbylBu.... Qeutc.................. a a T*WoOto........ AjrfKhOpAv&tt,.,, TBit............. ......... TnaeSw............. AatfeopBrtf<.... TBit...................... OUBTU-,........ K SO 63 2D 3? tt M pBrtWe BfeW.i siev* DuMiJaa tB-60 ttodieu tv,dim **fe t bbD tau SBBdfca *> Saadtei Sue leas MbHiobI fcar*lid iiur Ufl Aa). JaJarstoa, out* MO. 6 ia a it 8 22 SmiU MalUpfcJ&raeB'MartrBsQbataau: bfOBfAColiiU mkJ brwa*tietoeUM: me. Uoo; pcritMaaiU* ue O'aspfcoie Msams bt*ct*iab e bum *avr3 merafe aaft ptxfphml moct flfcrwla; tnuartot bwo^fiitu KhiM eoafiout rebpJwrO, aJvo!*r ffiunU aaM pari9Bulr eitultr pfofcfmtttm: muimtl aw. *M; bn'Mhfefarttal* bwS bFMicfiJUg SubWrarai. pertwoaeWoiar, aj jxiWaacutar bs ropbe aod fibrvcjtfc roU/rtiou e U |faBiIr enteraAt n*<ropl>|g 8C>po<tVi Uu> Mr pmUferBUee: WootWoiaeUMJ* BOd DroaUUU*; ti` t>roU by sedimentation in alcohol to isolate fibers approximately 2$. to 50* long. It is reported that the mineral uk say exist in fibrous Serpentine,--When introduced into rab bits by the intravenous route, serpentine dust produced withia three months a moderate form,* but attempts to obtain talc samples suitable for preparing fibers 20* to SO* in length were unsuccessful. The occurrence of talc as a long*fiber mineral would appear to be uncommon. degree of alveolar macrophage catarrh, with septal cellular proliferation. Cost particles could be seen particularly within perivascular macrocytic accumulations. Sn the case of the rat there is no comparable alveolar catarrh The third set of intrsttwcbeal experiments (Table 4) was specifically designed to mimic the dust exposures of the upper New York State industries and particularly to probe the influence of quartz oo the combined or sep arate pathogenicity of the other components of commercial talc. The effects <if these sub stances may now be scrutinized, EFFECTS OF TALCANB OF ASSOCIATE* at 12 days, but there ate some macrophage and eiultmudeated giant-cell accumulations at the angles between atoeoUx septa. In both the rabbit and the rat small isolated granuloraata, composed of muUsnuckatcd giant cells, well-charged fconiophores, unpigmeated macrophages, plasma cells, lympho cytes, and fibrocytes with intermingled capil laries, may be found at 12 months. These foci have a perivasculaf and peribronchiolar MINERALS ON TlSStnj distribution. Dolomite.'--The intravenous introduction of dolomite proved toxic to the rabbits, some dying while the injections were being made and others within a few days. Such animals showed a macrophage reaction in the alveoli by the third day, with perivascular and peri bronchiolar cellular accumulations. Occa sional eosinophile infiltrates were to be.seen. The lungs of animals surviving to 24 months showed no abnormality, a condition suggest The intratracheal introduction of serpen tine in guinea pigs provokes within the first month bronclual epithelial hyperplasia, with submucosal and adventitial cellular infiltra tion and scattered imra-alveolar koniophores. By the end of a year this condition has sta bilized as a chronic bronchitis, with bronebiolectasia and distortion. There is considerable epithelial desquamation, with some papilloma formation. ing ehber a complete recovery or a lack of Tale.--When introduced into the rabbit by chronic response in the first instance. the intravenous route, talc produces within 3J< 1 EFFECTS OF TALC DUST ON ANlUAL TISSUE cat month numerous focal areas of .alveolar macrophage catarrh and pleura! thickening through superficial fibrocytic and macrocytic hyperplasia. The talc spicules are universally distributed throughout the pulmonary paren chyma but avoid the lymphoid tissue, am! the alveolar macrophages do not yet show much talc, At the end of two years this talc is still present in the alveolar bronchial and vascular walls, and the intra-alvcolar macro phages now also contain some talc. Isolated fod of marked vascular muscular prolifera tion may be seen. More usually there is a perivascular alveolar reaction. Ewdaogiitis proliferans is commonly seen in the smaller blood vessels. Alveolar walls arc thickened through cellular proliferation. A moderate degree of chronic bronchitis and bronchioler dilatation is seen, together with broncho- pneumonic fod displaying a high proportion of macrophages. The pleural cellular pro liferation shews no advance on that seen at the end of the first month. The rat lung is apparently immune to the effects of talc introduced by the intravenous Fig. 1.--Pulmonary effects of talc inf^Wd ictra* (radically (Experiment 902--guiuea pig lung: re action one month after injection). Focal accumula route. No reaction is demonstrable at the end tion of talc-filled koniophores within pulmonary of the 1st month, and at end of the 15th alveoli. month a lew talc-laden macrophages may occasionally be seen in the alveoli. Practically all the talc introduced is still readily demon strable in the lumina of blood vessels by means of polarised light. When introduced into guinea pigs by the intratracheal route, particulate talc calls forth within one month perivascular and peribronchiolar focal intramural cellular accumulations comprising lustiocytes, fibrocytes, plasma cells, and rare eosinophiles. Dust-containing macrophages form irregu larly distributed confluent pneumonic patches (Fig. I)- Within eight months multiple foci of dust-filled koniophores in alveoli surround ing bronchioles and arterioles may be seen, but dust cells may also effectively occupy pul monary alveoli over extensive areas, produc the pleural surface, a fibroceliular sclerosis with subpleura! deposits may supervene. At the end of the first year the pleural reaction is well established, consisting of an outer fibrocellular layer, a cellular inner zone, and interposed foci of pigment-filled macro phages. The dense perivascular sheaths of cells are now seen to be spilling over into the proximal alveolar walls. Immediately adja cent to the blood vessels is a zone of lympho cytes, and somewhat further afield are some fibrocytes. The hypertrophy of the bronchiolar mucosa has advanced further, and there is now .some epithelial desquamation and muscular hypertrophy. At the end ^f the second year the dominant residual change caused by the tak is the ing a: solid effect. Some eosinophils and bronchiolectasia and bronchiolitis with epi fibroeyfe infiltration into peribronchial tissue thelial catarrh, Marked focal cellular depos is seen, and there is some fibrosis, with bronchsolar distortion and epithelial prolifer ation. Where dust-laden macrophages reach its and peribronchial fibrosis occur. Fibro cytes may nojv be seen to be Intersecting the massed koniophores, and a delicate web of 315 SCHERERS AND BURKAN collages is being laid down. Capillaries in vade these areas. * When particulate pale and quartz of the same particle-size range arc combined in the ratio of 3:1, the essential additional effects in the guinea pig on intratracheal injection of the mixture are perceptible within the first month. The effects consist essentially of a greater prevalence ot masses of dust-filled koniophores, with numerous eosinopbiles at the edges of the alveoli (Fig. 2A). There is a distinct tendency to alveolar septal cell proliferation, and in the cellular masses alve oli may survive as cuboidal-ccll-lmed spaces. At the end of the first year the combined talc-and-quartz lesion may be defined as a fibrocellular granuloma (Fig. 2B), and now numerous multinucteated giant cells occupy alveoli at the periphery of the koniophore masses. There is a distinct increase in lymphoid tissue not only in the parenchymal nodes and hilar nodes but also around the small blood vessels. At the fringes of the lymph nodes there is considerable macrocytic infiltration. The Uronchiolar distention and distortion pioductd by exposure to pure talc, though present, are less marked when the quartz is added. There is, however, more marked epi thelial desquamation, and there is more peri bronchial and perivascular fibrosis. TrtmoUu.--The reaction of the rabbit and the rat to the intravenous introduction of particulate tremolite (3/t and less in size), either of the soda-iron or soda varieties, is essentially negative. Most of the tremelite remains in circulation even at the end of the 29th month, though some particles may be demonstrable in alveolar walls and lymph nodes. However, even in the latter locations the dust may be within the capillaries. Very few macrophages are to be seen, and they are limited to minute perivascular infiltrates of macrophages and fibrocytes. When tremolite of similar particle-size range is introduced into the lungs of guinea Fig.^ 2.--Pulmonary effects of die intratracheal injection of talc combined with ^oartz (Experiment 902--guinea pig lung). A, reaction one month after injectico: massed accumulation of tak-fiUed komophores obscuring the alveolar pattern. B, reaction 12 months after injection; persisting macrophages; granuloma with slight fibrotlc changes and some eapUhry infiltraticm. goblet cells are now present in greater pro fusion. There is also oow store cellular infil tration and fibrosis of the bronchial walls, with macrophage discharge into the bronchial lumlsa. The intratracheal introduction of tremo- Bte fibers 20* to 50* long produces marked disease rapidly and extensively. Within one month the guinea pigs show complex masses Fig. 3.---Pidmonary efforts d tremolite ioifcted iatratrachefUf (Experimait $00--gviflti pig Jirog; reaction one month after injt5on), Gxnmgcdog erypt formation in a bronchlolar wall at the end of the first month under the influence oi tremolite Sbert 3* in length. of tremolite fibers trapped within, the bronchi and bronchioles. There h considerable bron chiectasia and distortion, with peribronchial fibrosis and cicatrization. Many of the long fibers may be observed to have penetrated into the wails of the respiratory passages pigs, many of the bronchioles arc observed (Fig. 4). At the end of 18 months the result to have undergone erosion at the end of the ant lesion is a marked fibroeelluiar diffuse I -- first month, with pcribroochfoZar Bbrocytic pnenatomtis, with marked bronchiectasis and asd macrocytic accumulation. The epithelium epithelial destruction (Fig. 5) and vascular i- - tends to be proliferated and to he desqua and perivascular damage (Fig. 6). This ex mated. G/ant macrophages filled with tremo* tensive lesion is directly comparable to the lite particles occupy the alveoli immediately mature human lesion and is even replete with adjacent to the alveolar ducts, and some tremolite bodies, i. tremoUte fibers sur scattered eosinophiks are to be seen among rounded by a brown iron-containing protein h, l. these cells. The reaction may, however, be sheath, showing typical terminal clubbing limited to slight bronchicfar evaginatioo and some measure of segmentation where it (Fig. 3). covers the shaft of the tremolite fiber. Many At the end of the first year there may be residual periarteriofer and peribronchiolar lymphocytic infiltration and isolated islets of particle-filled macrophages, Eosinophiles lie metaplastic cells are also found among the macrophages (Fig. 7). There is also a char acteristic pleural and subpleura) fibroeelluiar reaction (Fig, 8). scattered among them. The bronchiolar mu When particulate tremolite (3ft and less in cosa also shows considerable eosinnphilia. size) is mixed with quartz dust of the same When the tremolite is introduced in the form of particles up to 20* in length, tl>e spicules may be seen to be well dispersed and closely applied to the atveofer waifs of the guinea pigs at the end of the first month, Numerous macrophages msy also be seen containing such particles, but these dust cells arc by no means comparable in size to the size range in a ratio of 15:7 and introduced into guinea pigs by the intratracheal route, the immediate .effect is much greater than chat observed with cither the tremolite or the quartz alone}A permanent lesion comparable to that whk^i may be expected with quartz ahneis, hmArver, sof established. Apparently the healing^ process, wen when tremolite giants Seen in the preceding instances. There alone is introduced, also mitigates the quartz is a gra? abundance oi eosivopbsles and com effect Wijpn the first month there is an mencing fibrocytic infiltration of alveolar exuberant kooiophore and multinudeated walls. The bronchioles are a little distended giant-cell reaction which obliterates all sem and distorted and show incipient crypt for blance of preexisting pulmonary cytoarchitec mation. The latter change is seen to have advanced appreciably at the end of the first year, and tonics around the bronchioles. Many of the trapped bn&chioles are distended and dis torted, withfcpUhdia! desquamation and pro- 317 S03SPE71S AND DVRKAN Fig., <--Pulmonary effects of tremollte fibers 20e to SO* Jong infected intratrscheally (Expenmenf 995--guinea pig lung: reaction o&n cnooth after >tion), A, brontiaoVt choked with fibers and debris, showing breakdown of its wall and peribronchiolar celJutar reanion io relation to trapped tremoJIte fibers. B, high-power view of parmchymaj pulmonary reaction, showing tremehte libers, mscrophagea, fibrocytcs, plasma celjt, and occasional lymphocytes. Fig. 5.--Pulmonary effects of trerooHte fibers 20* to 50b Jong infected tntratracheaJJy (Experiment 995--guinea pig Jung: reaction 1$ months after ifljectksrt). A, snlervkHtal pulmonary fibrosis, with prevalent cellular elements and trapped tremolite fibers, B, distortion, distention, partial mucosa! hypertrophy, partial epithelial desquamation, and peribronchiolar fibrosis. XWEC7S Of TALC DUST Off ANIMAL TISSUE C* >rjRxt'.'.* '> * a //-'/ <>' I & to '*XH Pig. d,--'y&scufcf damage caused &y tremolite fibers 20* la SOm long (Experiment 99S---guinea fc'tg lung? r&ctym IS rocnths after mjeerion), A, periarteriol&r Shroris; fibers sparsely present I?, 'Ttswit ataost ottUeraitfi by fibroto teac&xx araoad trapped fibers. Fig. ?<--Fate iremoliie fibes 20* to 50* long lung tissue (Experiment 995--guinea pig h>&3: result 18 months after injection). A, tremolite fiber engulfed by macrophages with com- aaneiag clubbing < llte fiber ends. B, WrefriagWK* of Snapped fibers, some mtracellaSar and ccj-i extracelfelas. w,; *Vcj <. h/A SCHEPF.RS AND DVRKAN Fif. 8.--Paimoiiary effects of tremollte fibers 20# to 50* Jong (Experiment 995--guinea pig fegag: result 18 months after injection). Pleura! sclerosis suftptarai dominantly ceffnfar reaction aremi treowliw fibers. Iteration. Foci of necrosis arc present, and fibrosis is commencing at the periphery. The majority of alveolar walls are infiltrated with macrophages, and there is some perilym phatic komophore accumulation as well. At the end of the first year there has been a measure of recovery from the initial exag gerated reaction. Foci of massed komophores may still be found, but there is very little reaction around these cells. Necrosis is still seen at some areas. Small lymphocytic sheaths accompany some of the bronchioles and arterioles, and the bronchiolar epithelium has recovered in large measure. AnthophyUile.--The intravenous introduc tion ol particulate anthophyllite (less than 3p in size) produces minimal pulmonary lesions only in rabbits. The lesions are limited to macrophage proliferation and plasma ceil accumulation at pericapilfery and intraalveolar sites, and the reaction should be classified as inert An intratracheal introduction of anthophyliite in this particle-si*e range was per formed in spite of the essentially negative intravenous result. Ax the end of the first month areas of intramural and intra-alveolar cellular accumulation occur. Most of these are dust-filled macrophages, but there are several eosinophiles among them. After one year areas of irregular fibrosis may be seen to surround distorted and distended bronchi oles. Numerous areas of bronchiolar epi thelial desquamation with necrotic cellular plugs in the lurruna may be found. There are also massed peribronchiolar accumula tions of koniophores with commencing inter stitial Blscosis. Hie effects of the introduction of antho phyllite fibers in the less than 20p length range are comparable to the effects produced by the 3^ particles, with the exception that fewer macrophage masses are formed at points distant from the bronchioles. There is a greater tendency also for diffuse alveolar wall thickening through cellular infiltration and a higher proportion of fibrocytes to macrophages where cellular reactions are provoked, especially in the peribronchial tis sues, The birefringent particles all seem to lie in relation to the fibrocytes. Bronchiolectasia and catarrhal bronchiolitis reach a some what more advanced degree (Fig. 9). The long-fiber anthophyllite (20^ to 5Q/i) has an enhanced and eves more rapidly in jurious effect on the guinea pig lung. Within one month if produces a marked and exten sive focal peribronchial fibrotic and cellular reaction, consisting mainly of macrophages, fibrocytes, and eosinophilcs with areas of lymphocytosis (Fig. 10). Anthophyllite fibers and spicules are embedded within these cells, and some may be partly engulfed by giant cells, Areas of necrosis occur. Bronchitis and bronchiolitis with distortion and disten tion are present, and the lumina ol such pas sages contain necrotic cellobr debris. At the end of 12 months a more advanced stage of essentially the same lesion may be seen, with, however, more central and irregular fibrosis within the nodules of reaction. There is now some bronchiolar stenosis as well as ectasia. BFfSCTS OF TALC OUST ON ANIMAL TISSUE Pig. 9,--Pulmonary lesions caused by authcehylUte fibers less than 2&* lone (Experiment 85--gomes pig long: result 12 months after m/ectwao). A, mixture ef maercphagea Sfcrocytts, ocmmul plasma celts, end collagen strands. &, bfondyoleetasu within aa area of reaakm; multiple evaginadons create a cystic effect XiJhts anthqphyllite fibers &t>d quartz arc mhced with each other in a ratio of U : 9 and introduced info guinea pigs, a marked subpte'iiv.l cellular reaction, confluent mural pioUfcrations, and perivascular cellular accu mulations may be found within one monthSoNd foci of macrophages occur, and there is commencing distention and distortion of Fig. 10,--'?u(mopary effect of anthnphyllite fibers 2fo to 5&u long injected sntrstracheatfy (Sxperimsut S93--cruinea pig lung: reaction one momb lifttr fojAction), Section shows rapid degeneration of bcenthfok, pcribroncbioSar /kminantly ctifukr deposit in relation to trapped fibers, but failure to im'dve the lymph node. bronchioles. By the cud of a year the lungs are occupied by multiple masses of cellu lar reaction consisting mainly of fibrocytes, though some macrophages are still present. Advanced multilccufar bronchiectasis may be found within these cellular zones. An intercsbtjg feature of the reaction, which shows forcibly the modifying influence of the anthcpfeyjjjt* on the quartz, is the fact that, though such cell masses may encroach on and surrooBd the jym^oid nodules, they do not involve them, Small foci of acellular necrosis occur *n some of the larger cell masses, but there is no distinctive tendency to fibrosis, such as may be seen in a pore quartz lesion at a comparable stage. COWBIN0 EFFECT OF lEBMGLiTE, AKTHQPHVLUrt, A WO 7ALC The purpose of this experiment was to at* tempt to define the relative influence of quart? on a mixture of components which simulates the natural talc product mined in upper New York State. The study was there- SCHBPBRS AND DVfiKAN fore conducted in two stages, viz., with and Thus it seems that the basic reaction to without the quartz. the presence of any of these dusts is a macro When no quart* is included, tfre initial phage catarrh into the alveoli, the cells be reaction to talc, tremolite, and anthophyllite coming engorged with large particles so is very mild. At the end of one month there rapidly that they remain immobilized asvd tail, is slight bronchiolar epithelial catarrh and except in rare instances, either to return to some plasma cell infiltration into the bronchi* the tissues or to be extruded from the lung tar mucosa, Isolated stratt fed { dust-fitted via the respiratory passages, H is possible macrophages may be found. At the end of a that this is merely a mechanical result due year the ares of reaction around the pig to their large size. On the other hand, it is mented macrophages ts somewhat more ex possible that the koniophores are actually tensive and includes some capillary hyper paralyzed. They certainly do not tend to emia, Such areas may occur in relation to undergo necrosis; not are collagen or other the bronchioles and subpleurally. A little types of fibrous elements stimulated to invade bronchiokr distention and distortion may be the cell masses in the majority of instances, seen. except when the component fibers are long. The addition of 14% quartz to the talc, The degree to which fibrosis supervenes tremolite, and anthophyllite mixture rapidly depends on the length of fibers rather than provokes massive focal lesions consisting of on their chemical composition. Thus when macrophages and fibrocytes with scattered the minerals have been reduced to 3ft and giant cells. Multiple foci o? diffuse alveolar less in maximal dimension, they have wall thickening due. to macrophage invasion practically no fibrogenic effect. On the other and septa! cel! proliferation also occur. In hand, the 2Qp to 5C*u length tremolite and the air passages there are incipient epithelial anthophyllite fibers produce extensive re hyperplasia and submucosal plasma cell or gional fibrosis, Unfortunately talc could not lymphocytic infiltration. At the end of a ycaj be obtained in this fibrous form, so that it this exuberant cellular response still persists, is not certain wlwther this rule applies to- but fibroeyte accumulation is limited almost talc also. It was observed, however, that talc to being a. fringe j&t-nonventm. Ttte d'iMor- evokes fibrocytes, but the presence of these lion and distention of the bronchioles and cells does not tend readily to lead to collagen epithelial catarrh have also progressed some deposition. what, but the degree to which this has oc curred is by tw means comparable to the lesions which may be provoked by either long-fiber tremolite or amhophyllite alone, coamfcMT Though one must acknowledge at the out set the limitations of the techniques em ployed in this series of experiments, the diversified results obtained, not only by ex ploiting different mineral* but also through modifying their particle sires or varying the route of introduction or the species of experi mental animal, justify the inference that at least some progress has been made in eluci dating the role played by compcrvmts of com mercial talc in producing disease and the mechanisms by which the terminal results are achieved. Attention must be drawn to the triple localization of the lesions produced by talc, tremoHte, ? anthophyllite, namely, at peri vascular, peribronchiolar, and subpleuraJ or pleural sites. In addition, cellular accumula tions having no such apparent topographical relation to the blood vessels, air passages, or pleura may occur. It is possible, howevzs, that these macules are merely examples of die standard lesion cut at a tangent. The lymphatic tissue escapes almost entirely, and alveolar walls are not affected except near the focal deposits or when quartz is present too. The marked tendency to bronebiofar distettfsen Slid distortion is readily explained when large masses of sharp elongated fibers are trapped within Jht bronchioles or when there are extensive peribronchiolar cellular 322 EFFECTS OF TALC DUST ON ANIMAL TISSUE masses of fibrottc cicatrization. The mecha nism is less readily apparent when such obvi ous causes are in abeyance. The mineral par ticles could oot be readily demonstrated in tlie bronchial wall except when advanced disease was present. On the other hand, it must be granted that we do not yet know the lower size range of particles of those min erals which may be active. The lack of secondary infection in spite of the marked pulmonary changes observed is remarkable. Unfortunately the study was not elaborated to include observations on the influence of the talc minerals on the course of tuberculosis. Such a project would be worth pursuing in view of the conflicting reports concerning the prevalence of tubercu losis among human talc victims. It would, however, involve a costly inhalation study. Contrary to expectation, the addition of quartz did not materially enhance the patho genicity o? the talc minerals. Indeed, there seems to be some indication that the fibrogenic effect of the quartz is reduced by the presence of talc in particular. This may be explicable on the supposition that if all the konfophores are effectively 'occupied and immobilized by the talc the quartz cannot influence them to the contrary and thus does no? truly enter the body, remaining trapped in the koniophores lying in alveoli and thus truly still outside the body. The lack of a lymphoid tissue response favors such a simple and mechanistic explanation. On the other hand, the difference in reaction may be more subtle and dependent on chemical or physical interaction between the quartz and the other minerals. While there are these evidences of oppos ing or inhibiting actions, and, as has been shown, they are not limited to quartz, there is also some suggestion that in certain com binations separate components may augment one another. This applies particularly to the combination of quartz with trcmolite or an- thophyllite. The. successful experimental production of a tremolite body provides strong evidence that the bodies found in human "talcoris" * are truly provoked by the tremolite com ponent of the talc dust. Comparable bodies were not demonstrable in the anthophyllite series. There is, therefore, more than length ol fiber required to cause them to develop. This feature firmly links the animal path ology to the human disease. Indeed, this series of experiments elucidates most satis factorily the nature of the human talcotic reaction and the factors responsible for its production. At the same time it sheds further light on the asbestos problem while confirm ing certain observations previously recorded concerning silicosis. Furthermore, the rela tive immunity shown by certain animal types serves to confirm the general concept of vari able susceptibility of man and animals to disease. SUKMABV The pulmonary response of rabbit, rat, and guinea pig lungs to dolomite, serpentine, talc, tremolite, anthophyllite, and quartz, either separately or in combination, was explored by the intravenous and intratracheal tech niques. Dolomite and serpentine arc relatively inert. While talc is dominantly eytogemc, tremo lite and anthophyllite have both cytogenic and fibrogenic propensities. Quartz modifies the effects of these sub stances. The effects of these substances arc differ ent from the effects of the substances in combination acting singly. Talc, tremolite, and anthophyllite all tend to damage the smaller respiratory passages and blood vessels to a variable.degree. The long tremolite and anthophyllite fibers produce rapfdj and grave peribronchbUr le sions. i iREFERENCES 1. SehepersjG. W. H, and Darken, T. M.: The Effects f{Inhaled Talc-Wining Dust on the Human Lung. A. M. A. Arch. Indue Health IS? 182-197, 195S. $ 2. Dana, E.|S.: Textbook of bfineralcgy, Ed. 4, revised and er.Ujged by W. E. Ford, New York, John Wiley & Sorts, Inc,, 3932. 323 1 Dlxe JSiotoficat Cffch of (Zaicinecl CftfpSum A** Esperinentei Study o* Amro} Lang* 6. W. H. SCHEPE65, M.D.. B-SeT. M. DURBAN, M.I, ed A. B. DtLAHANT, $omw Uie, N. Y. Studies dealing with die biological effects of calcined gypsum dust on experimental animals were initiated at The Saranac Labo ratory during 1933 by the late Leroy U, Gardner, M.D., Director. Although the in vestigations were pursued over many subse quent years, only partial accounts of the results have been published thus far.* Car ried along by the momentum of a succession of studies of increasing importance, Dr. Gardner had to divide his time among many investigations, and his ambitiously planned jnonograph on The Saranac Laboratory ex periments with calcined gypsum dust re mained \mvmUcn. In the present paper the results of a com prehensive series of long-term inhalation ex periments, with the conduct of which two pf us (T. M. D. and A. B. D.) were inti mately concerned, will be recorded. Owing to the broad range of the experimental pro gram, the paper must necessarily be limited to the presentation of an over-all survey of the investigations. More detailed treatment of individual histological aspects will be given in subsequent papers. Effort lias been made to avoid repetition of what has already been placed on record by Gardner, and though for the sake of completeness and logic reference has to be made to such matter, most of the material now presented will appear for the hist time, and the interpretation of experi mental records and slides are our own. MATERIALS The calcined gypsum used in tf* experiments was the standard product of plaster mills and, being a commercial material, varied somewhat io composition from time to time. The following ap proximate estimate of composition and partiek'&ise range refers to the product received during the early part of the experimental studies; for materia! forwarded later the per cent of hemihydrate was higher and ol calcite, lower: Approrfnste PsnkkSlM CoapMMit fUnlbydrate 0i60*H.0,. Aatrjfirrt* C*S* ............... CsfelM CeCO................ `Tfesd-bumed CTpevta" Odru SfO ............. PMtcrOCO. ijl ........................... A10 j "04kH>Wl ITPSTO" ... Per Cent 3t 16 S <1 I 500 Bta*e, 1-75 v-a 1-40 1-J0 Avermn, A t i 1 .. .. 1-40 6 The quartz was a commercial product supplied as a finely ground powder with an SiO* content which exceeded 99$. The tubercle bacilli used for the infection phase of the study were of the It lowvirulence human strain whose haberculoffenk pro pensities and cultural cliaracteristks have been well documented.f Recorded for publication July IS, 1955. Director (Dr. Schepers), Asscoate Director (Mr, Durkin), and Research Associate (Mr. Dclaharu). The Saranac laboratory, * References 1 to 4. SCOPE OP EXPERIMENTS The present report will deal with tlte re sults obtained In inhalation experiments in t References S and 6. BIOLOGICAL EFFECT OF CALCINED GYFSVM DOST which guinea pigs were exposed to dust under various environmental conditions, as follows: -- Olcuwd gypsum dust lor 24 months. Calcined gypsum dust for 24 months and then normal air for 22 months. Calmed gypsum dost for 24 months and then quartz dust for 18 mouths. Quart! dust (comparison) for 18 months. Caldncd gypstnn dust for three weeks artd then, alternately, quartz dost for one week and cakioed gypsum dust for the next week, with a continuation of (his program of alternating weekly exposures for 24 months. Mixed dust composed of equal parts of calcined gypsum dost and qtaru dust for 25 months. Mixed dust composed of equal parts of cakioed gypsum dust and quartz dust for 25 morttlu and then normal air for 12 months. Mbced dost composed of two parts of ealdrted gypsum dust and one part of quanta dust for 29 months. Calcined gypsum dust for $ months, then infec tion with R, tuberck bacilli, and tbei caldned gypsorti dust for 18 months more. Calcined gypsum dust for 25 months, then infec tion with R, tubercle badllj, and then normal air for 12 months. Mixed dust composed of equal parts of caldned gypsum dost and quartz dust for 3 months, then infection with R tubercle baafii, and then the mixed dust for 27 months more. Infection control S tubercle bacilli for 22 moaths. EXPERT MENTAL TECHNIQUES The inhalation experiments were conducted to $ ft, cubical rooms. The animals, kept in cages along the sides of the room, were exposed to the aerosol for right hours a day, five and one-half days a week. During such periods a rotating paddle device created and maintained m the room an atmospheric suspension of the dust under study, For the real of the time the air m the room was free of any substantial amount of dust Periodically, In most cases at intervals of a few months, animals were killed for study, so that the progression of any tissue reaction to the dust or to any infection given to rite animals could be closely followed Chemical analyses to estimate the amonnt of dust retained in the lungs were carried out on some animals. During each experiment the dust concentration was checked frequently by the implnger method. Infection by the R, strain of tubercle bacilli was achieved by means of the intratracheal insufflation technique perfected to The Saranac Laboratory.* Each animal recaved 6 pus's of the stormier from a suspeotioo of R tubercle bacilli containing 15 to 20 tingle organisms per oil-immersion field l. EXPOSURE TO CALCINED GYPSUM DUST ALONE The results of this experiment on 21 nor mal uninfected guinea pigs have been sum marized in Table 1. The guinea pigs -were exposed to only calcined gypsum dust. For the entire exposure period the average dust concentration was 448,000,000 particles per cubic foot of air. The guinea pigs were ex posed to the dust for periods up to 24 months, animals being sampled at various intervals. At the end of 24 months the sur viving animals were removed from dust and transferred to a normal atmosphere to con stitute the second part of this experiment. Sonic of this group lived as long as 22 months after the termination of the dust ex- posure, and samples were taken at 3-month intervals during this period. Twelve of the twenty-one guinea pigs died of pneumonia or other pulmonary lesions. This mortality trend whs widely dispersed over the whole experimental period. Deaths were slightly commoner in the earlier months but perhaps not significantly so. It would seem that the death rate of 28.5% per annum was slightly high. The mortality trend in guinea pigs in one of The Saranac Labo ratory experiments with a comparatively inert amorphous silicate dust was about 22% per annum. The fact, however, that all deaths in the experiment with calcined gypsum were from respiratory causes may be meaningful. In spite of these observations no signifi cant gross signs of pulmonary disease mani fested themselves, and no nodular or diffuse pneumoconiosis ensued. In isolated ani mals pigmentation commenced to appear toward jthe end of 10 months, and minute foci of jatelectasis could be seen. After a year of(dust exposure a minimal amount of pigmentotion became an almost constant sign, and atelectasis was more frequently observed. The microscopic counterparts of these features will be described in further 4, *4 SCHEPERS BT AL. X1.--SioJftpveot Attic* / Canned C>,pm Curl Guloea pjgs Were Cofltieooosly Exposed by Inhalation to the Dust Ufitil Death fig. He. SJSffl e SI ts a 64 a 63 44 42 TO <3 & 46 41 B U TO tt H u t Dan 64 to m *S3 m St m ax G2 m tu <20 47S oo no m m m ns m m FsU DM DM ZBM DM DM DM EBrt DM DM BUM DM BUM DM SQM SUM SUM DM DM DM gnu* tnruA Caor it Exua PbbumoU Fajumoaii PftftUDOOli PjKBTOOnit PBfOZBOSta p* 4 FaeumoDJa `TaaeaUi Fseunfttta PMMar PvHoontrj abate** Dasusonla PWSflKWi* TUtM Beactfos Is LUOS follMUTt Poi3 FJ*. Focal Pi**- BtSUUOfi awMtaois SMBUUOO HodM SB?*rrd . XodB .. .. .. ,, +4 .. +4 +4, + ,, + ++ +4 + ++ 4 ++ .4. + 44 + 4 ++ 4+ 444 .. + 4+ .. ,, Srabob; 4-. Dirac resettop; 44, moderate faction; 444. adcaaM mettoo. detail later, but is summary it may be stated tliat although a diffuse eelWar reaction ulti mately ensued no fibrosis attended this process, The lymph nodes showed irregular enlargemeot of a moderate degree, character ised by growth of the follicles more particu larly. Only rarely could pigmentation be seen. There were no signs of degeneration, necrosis, or fibrosis. Ten guinea pigs were left in normal air for periods up to 22 months after they had been exposed for 24 months In the calcined gypsum dust chamber. Only tout oi the animals died naturally, and in only two of them was pneumonia the cause (Table 2). Pigmentation persisted in the majority, but atelectasis soon disappeared though diffuse cellular proliferation could still be seen. In the lymph nodes a low-grade chronic inflam- Tabce 2.--PiolcgicoJ Action cj Calcined Gtfsum Dutl Coinea Pigs Were Continuously Exposed by Inhalation to the Dust for Twenty-Four Month* and Then Were Transferred to Norma! Air Where They Remained Until Dead) Gotftea Sr. Sio, SSMt 69 61 as 17 TO TO to ExperaR IftDwl, Den tt n u u 46 41 68B 666 tee 966 Fate SQM SUM DM DM DM dim SSIM SUM ftUed SQM Caw of Death 41 <0 <0 PstutnoBfa Fftcmsoota ETOeuelUacOaolB Poce) pi*. aesuuofi 4 + r...TPtOmftaary I.ra*b Ng -- Focal Pi*. Eala^M Atatelaat* sKBtatktt Kodcs 4 + s< + 44 4 4 4 + + 4 t 4+ 4+ 4 4+ Sjabois; *, itJefii reac'Joa: ++, aeoMnUe reaetfea; +44. adcaoM mctlofl. 326 BIOLOGICAL EFFECT OF CALCINED GYPSUM DUST naatory reaction developed daring the first two months the animals were m normal air, but during subsequent months this sign re* ceded. Similar observations teve, on occa sion, been made on adult guinea pigs sever exposed to dust. Until the pre cise and specific underlying histopathologic mechanism is appreciated in the case of the gypsum-exposed guinea pigs, the significance of the occurrence of these lymph node changes may be missed. The results of this study ae given in Table 3. It will be observed that only four of the animals died spontaneously. This rate of 23% for an 18-month period is actually lower than the average mortality trend of 2\% per annum in our dusting experiments with an inert amorphous silicate. This virtu ally suggests that the gypsum exerts some measure of protection against the action of quartz. It must be recalled, tiiough, that these animals represented the hardiest speci- Table 3.--'Combined Biological Action of Calcined Gyftum Dtui and Quart* Dust Guinea Piss Were Exposed by Inh&fcticei to Calcined Gypsora Dust for Twenty-Four Months and Thereafter to Quart* Dost Until Death Bur. Go&tfa Quart* Wc. &ML Xe. Days Fate sene M DM 63 as EQirt 0 3 SUM u m BBrt 6? as jrflirt as ut DM N 1( gffirt u Hi giiwt us HJDrt 67 &) Dirt 96 sus Klflrt m SUM m 966 K1TM 71 CS SUM n 4EB KlBrt n OT SHrt u m grow Cause e{ 1*4ti f VimubuaEa J 14 4 FQ40(TKla ............ .. Jfltrwrcpft Sefcboee ot FrtBBtocoatoila SomOos Ib Ful&soasrr lyaplj Xodaa OeDuJar DestenUoB Tifraea. Atefec. laO. ^ $ Ssiarve- Firnss. Dec^otntioB iaUws 4 Urta 4 BraBob TfBro&t Necrotte anst 4^ t4 uoob Bjttee Nscfotte .. 4 4 .. 4,, 4+ 4 *4 44 44' 44 .. 4+ .. + 4 44 44 44 4+4 44 .. .. ,, ,, 444 44 44 +4-4 4 .. +4 4 44 ,, 44 4 .. 44 . 4 4 ,, 4 4 44 4 44 44 444 +4 4 44 4 44 444 .. + , 44 44 44 4 4 +4 44 44 4 +44 44 44 4 44 44 4 .. Sjatbeb: +. lit metioo; +4. BrtnaM resfltSea; 444. adruoad reaeOoB, a EXPOSURE TO CALCINED GVPSUH DOST FOR Tw*rr puu* followed by pro longed EXPOSURE TO QUARTZ DUST In order to determine whether a prolonged period of exposure to calcined gypsum dust would modify the usual harmful effects of any quartz dust which might be inhaled later, an inhalation experiment to investigate this question was conducted. A group of V guinea pigs, after being exposed to a calcined gypsum aerosol for 24 months, was trans ferred to another room in which they in haled a quartz aerosol for periods up to lI8 months. The average value for the mim- 3>er of particles per cubic foot of air was '-448.000,000 for the calcined gypsum dust and 320,000,000 for the quartz dust. mens that survived the two years of gypsum exposure, and so protection may, be only illusory. That the gypsum does have a protective influence, laowever, is revealed by a study of the pobnonary tissue reaction. While pigmentation increased progressively, even tually tattaining a geometric pattern and finally producing mustard-colored patches, it, nevertheless, was not as extreme as the pig mentation which occurs in animals exposed to quartz dust only. Atelectasis was present in animals in the earlier (phases of the quartz-dusting period and disappeared bawd the end of the ex periment. The atelectasis thus may have been a perpetuation of that seen in the later * 327 t SCHEPERS ET AL. phases of the experiment with calcined gyp sum dust alone. * Consolidation, dominantly cellular in type, appeared toward the latter part of the quartz dusting phase. From about 10 months on ward, areas of cellular infiltration could be found. Strands of fibrous tissue appeared among these areas toward the end of the 12th month. Except in the guinea pig killed last of all, this fibrosis remained moderate in degree througtout the period of study, In this animal and in that one preceding it in the series, some abscess formation could be changes and necrosis appeared Brsi toward the eighth month and became increasingly more prevalent later. Associated with these parenchymal pulmottary changes there was a marked catar rhal bronchiolitis in the quartz-exposed animals which was not seen m those which had first been exposed to calcined gypsum dust. Hie lymph nodes likewise showed a considerably enhanced and early expansion m the silicotic control guinea pigs, with progressive fibrosis and ultimate hyalimzation. T*tLE A.--Biologitoi Action of Quarts Dmi Control Stud;: Uninfected Guinea Pits ffjrposed b> Inhalation to Quartz Dust Alone Until Death 6me s14acc of BBcoffe Jlteeawiifc Ertd*a of BSceeia FttkToSoUgMar?ScLareoupeSsSlaode ,.....n * Outage x&9> me, fare. Pif&Mn- So. D*r ru Uttoo tt-41 03 s s 123 K ,, i iU f t*s- ++ s Be K ,, e m s ++ & 128 s ++ es 6i X ++ Atn) Adb* Bob* 4' OeBaitr &ercr*ttoa PtaonU BxoMbto. iftfit. BOl trcUos yjDree* Hr*Um R*erorte + 4 ,, ++ +* +-+ ,, 4+* ++ + 4- + 44-+ +++ + + + +++ +++ ++ 4-P +++ +++ ++ +++ +++ +++- +++ NtH U&UMlOB 4+ +++ 4-H++ ++ ++ 4' CercsmtSeB Pfbreq* B73Xtf + ++ +4' H* +++ ,, +++ 6vstt*& +, ftUgtti rtacUee; ++, (BoStnu reaction: I++, ftMiloo, seen. Necrosis was, however, conspicuous by its absence in earlier phases. No hyaline changes occurred in the lungs. The pulmonary lymph nodes allowed moderate enlargement only, with no tendency to increase in size toward the end of the experiment. Pigmentation remained minimal, but some hyaline fibrosis occurred toward the 14th month and in some instances was preceded by isolated areas of necrosis, These changes are the more sharply shown to be indicative of the protective action of the gypsum when Tables 3 and 4 are com pared, In chc latter table, representing the control group cxj>osed to quartz dust only, cellular infiltrates are recorded as having appeared within two months and were quite marked by the eighth month. Fibrosis could be discerned within 4 months, and it in creased progressively, reaching a marked degree toward the 10th month. Hyaline This comparison suggests that the prior inhalation of calcined gypsum dust not only retards the onset of the major effects of inhaled quartz dust by at least six months but also materially diminishes the degree lo which they evolve and modifies the nature of the reaction to the quart* dust. 3. ALTERNATING WEEKLY EXPOSURE TO QUARTZ OUST AND TO CALCINED CYJSUV DUST In the preceding study efie gurnea pegs inhaled calcined gypsum dust alone for a long period and then quartz dust alone dur ing the remaining time they resided in the dust chamber. Some of the protective action of gypsum against quartz could, in theory perhaps, be explained on the basis of selec tion, for it must be recalled that quartz dust ing was commenced only after 24 months of residence in an environment containing calcined gypsum dust in atmospheric suspen 32$ 4 BIOLOGICAL EFFECT OF CALCINED GYPSUM DOST sion, and alter the weaker guinea pigs had died off. A group of 10 guinea pigs was therefore exposed to calcined gypsum dust lor three weeks and thereafter alternately to quartz dust for one week and to calcined gypsum dust for the next week. During each weekly period the animals were exposed to the dust for about 8 hours per day for five days aod about 4 hours on the sixth day, or a total of 44 hours per week. This alternating weekly routine was kept op for two years. the second year of exposure. The pulmonary lymph nodes likewise showed the same pat tern of reaction as that which occurs in the silicotic guinea pig. Unfortunately, animals were not killed prior to the eighth month; hence it is possible that a measure of early protection was ex erted by the gypsum. The degree oi reaction seen in the animal accidentally killed after three months was, however, less than that found in the quartz-exposed animal at two months, and at the eighth month the animal TxBt.F. Combined Biolopieal Action of Calcined Gypsum Dust and Quarts Dust Guinea Pies Were Exposed by Inhalation to Calcined Gypswn Dust for Three Weeks and Thereafter Were Exposed Alternately to Calcined Gypsum Dost and to Quarts Dust for a Week at a Time Until Death rpo< lit. So. HSU S 6 K U 11 s IS 10 Dual, Dr BM m a m n MS US CBS m Fit* D E x D D D E S. g Caufie et Etttb Transi ...... Cbrcote PBCBtBOnfn CatronJe pMtunonli CbroaJc pJMOBO&la OSroaJe pkarWy ......... Uterocecptf Srfctaae o* Pa^taoesmlosi* Bctnies to PuiiaoBary Lras&#o6a GeQoMr Deteaeredos DetamBoc rafi!tf*006 , "*........ .. CeSaUr. Broad)' &r* S&fr 4fo> ' emu ' Foeel Offluw ' Fibrosa las* erocie traQoa ftbroat ayt&M erode 4 4-H- 4 4 44 .. .. 99 44 4 + 44 +44 44 4- 4 + - - 44 ,, 4 44 - 44 444 44 4-H- 44- > 4 44 444 444 444- 44 4-H- 44- +4 44 444 4-44 l i 4 4 4- 4- 44 - 44 444 4-4-4- 4-4- 4-H' 44 .. ..444 4-H- 4-4-4- -H-f .. 4 444 444 4 4- ..444 4-4-4- 4-4-4- 444 + 4 44 44 44 SrdtbetaJ +, afigbt reeetioa: 4-f, noOwsi* nnaos: < 14, aevarteed Teietton; 4-H4. verr roaettoa. During this period the average concentration front the latter group showed a considerably of the calcined gypsum dust was about greater degree of pulmonary and hilar node 448.000. 000 and of the quartz dust about reaction than that observed in animals ex 128.000. 000 particles per cubic foot of air. posed to calcined gypsum dust for a com The results of the experiment are summa parable period. rized in Table 5. The point which has not been settled by Four of the ten animals died of pulmonary this ^tudy is whether this slight retardation causes toward the end of the first year, and of the pneumocontotic response was due to the dose grouping of these deaths suggests the fact that the animals received a total an intercurrem infection. The total pulmo dust load about half as great as that which nary reaction was not unlike that seen in die animals exposed to quartz only (Table 4). Marked bronchiolitis was a prominent feature near the end of the first 12 months. Cellular infiltrates appeared focaily and dif the uiimals inhaled in the control experimentlwith quartz dust only. By comparison with i the preceding experiment it would seem] too that any inhibitory action which the gypsum may possess is not so much fusely, and degeneralive changes followed dependent on the concurrent presence of rapidly and reached a marked degree during the gypsum and quartz in the lung tissue J 229 SCHEPERS ET AL as on the biological responses induced by the gypsum. * EXPOSURE TO A MIXTURE OF EQUAL PARTS OK CALCINED GYPSUM OUST AND QUARTZ DUST Another aspect of the possible protective action ot calcined gypsum dust was investi gated in an experiment conducted with a mixture of equal parts (by volume) of calcined gypsum dust and quartz dust. A group of 35 guinea pigs was exposed to this mixed dust for periods up to 24 months, and at the end of that time 15 surviving animals were transferred to a normal atmosphere where they lived for periods ap to 7 months. The average dust concentration of the mixed dust during the experiment was 318,000,000 particles per cubic foot of air, and the aver age concentration of the quartz particles in the mixture, determined by using dilute acid as a collecting fluid in the impinger flasks, was estimated to be about 124,000,000. Although the material in the dusting machine was composed of approximately equal parts of quartz and calcined gypsum, tliat ratio was somewhat different for the aerosol derived from the mixture. Table 6 shows that the amount of quartz was less and the amount of gypsum greater in the atmospheric dust than in the parent mixture from which the aerosol was derived. For dust that had settled on top of the animal cages, the situation was reversed, and for th/s settled material the quartz rowent was higher and the gypsum content lower. This Take &--Composition of Aerosol taut of Settled Dust in Comparison with Porenl Hopper Mixture Which Was Composed of E<ptal Pcfames of Calcined Gypsum D%si and Quarts Dust All Sample Were Dried at HOC Before Anslysh CoBtfeueBt BtOi ................ a-sa. QtOOs 1 Soccer Mature. Fee Crt Fe.O*. AJtO* ......... ,. ignflfou !^5 ......... Tout.................. oa Settled Aerosol Usflt 00 Top of 0*?. Owes, Set Cent Per Cent isa SIS 694 8S S.t 0.9 0.9 6t tx WOs ms condition was probably due in part to the larger average size, and therefore more rapid settling rate, of the quartz particles. The results derived from this study are summarized iu Table 7. Once again it was found that more than one-half (in this study 55%) of the animals died of pulmonary causes, the majority of these succumbing within the earlier phase of the experiment. In spite of this, there was very little evidence of a pneumoeontotic response before about the 1Sth month. From that stage on the total reaction was that of a dominantly cellular dif fuse reaction. Atelectasis was a conspicuous feature in one instance, and bronchiolitis oc curred in two later rases. But both fibrosis and necrosis were in abeyance until about the I9th month of exposure and even then re mained limited in their extent or intensity. The pulmonary lymph nodes likewise showed but minimal reaction. Though they exhibited a uniform tendency toward mod erate enlargement, degenerative changes, such as fibrosis, hyalinixation, and necrosis, en sued in but a few cases and to a minimal de gree only, The concurrent exposure to gypsum ,and quartz, therefore, appeared to have retarded and modified the influence of the quartz Gn the guinea pig lung, When the 15 surviving animals were re stored to normal air after a full 24-month period of residence in the gypsum quart* dust environment, the high rate of pulmonary deaths continued (Table 8), Over the nearly eight-month period of survival, 53% of the animals died of pulmonary causes. At the time of their death, the majority suffered from a chronic pneumonia which was partly based on the diffuse cellular quartz-induced infiltrates in the pulmonary parenchyma. At the same time there was a very marked type of fibrotic response, with hyaltae changes m some instances, Unlike in the frankly silicotic cases, however, there was but Unit tendency toward necrosis, though a dust-engendered abscess was found in at least one instance toward the end of the experiment. The pulmonary lymph nodes were moderately enlarged and the sea? 330 i 4 BIOLOGICAL EFFECT OF CALCWED GYPSUM DUST ?asls 7.--CcmtHn*d Biohirieal Action of Calcined Gyps*** Oust end Quarts Dust Guinea Pig? Continuously Exposed by luhafatiec Until Death to as Aerosol Derived Irofi) a Mixture of Catdaed Gypsum Dost aod Oturtr Dust is Equal Proportions B*W>* 0099 Guinea u ElC. !>* He. Days MB a C a> s is IB s s JJ m U Ui u 45} a 6 M 93 m IS w to *a St 4*i s a ** os SI u* 9 Pi B to as 9 Fate DM dm dm Died dm BOM DM DM bum XUled DM DM KUefi PM DM SS*d EDM rat** gfIVd BOM UUnseople BvtdM'e < S'seossoccAlBCiB 2.7iaisBt)Htotdtecteoearr > ,............................................................. ..... --u-------------- ---- ---------- ol Deitb FnasaoeU FseuooBli Faeumoala Brotxbi. atatoeHUi CWUuUr l&fiitTBtUB Foeal 4^ , EMflBH , PeteoarattM) .................. N*. Heroes grotto i Macro* Demaent&ea oBaae . laiU. Hji> IikUob SSCAUja line erotic 44 ** .. 4 44 4* s4 .. t -f tH> FaeuBBelK 4 44 ,, 44 4 Bmpyena 4 9S 4 44 . , 444 .. ,, .. 44 AeoaoBlk ,, 44 ,, AO ,, 4 .. ...... 44 44 44 ,. 444 .. 4 44 .. FsconoBlk 1 ,. 44 4,, 4 4 .. Emwrens* ., +44 .. 444 .. ,, .. 4 A4 44 4 Empyema Empyema 444 ,| .. 4 444 +4 4 ...... 44 4+ .. A, 4 .. .. ...... 44 .. 44 44 44 +4 .. ,, 44 44 4 4 4 4 .. 4 +44 444 4 4 44 +44 444 4 444 44 44 .. .. * Brabete.' +, alight rwtton; ++, tnortenU Teaettoo: 444> *drtoaxt metsoo. of moderate to marked diffuse byatinizatSon in the majority of cases. 31 would seem, therefore, that the concur rent inhalation of the calcined gypsum and quartz dust, though retarding the mitigating effects of the latter as Jot^ as exposure is actively continued, ultimately leaves the lung tissue diffusely vulnerable to the effects of the quartz dust. Apparently after the exposed animals have resided for a period in normal Tasj-e &--Biological Action of Calcined Gypsum Dust and Quarts Dust Gdaca Pigs Were Exposed by Inhalation for Twenty-Four Months to so Aerosol Derived from a Mixture of CaJdned Gypsum Dust and Quartr Dust ie Equal Parts and Were Thereafter Kept is Normal Air Until Death arttf BBS of Dust Ftt, WO- m# B o B IS IS a S3 ns^ D*7* b is a e s to u n< Face X1M Bfflad Pled SKUA 2>M DM Died DM IS IM a itt EM e ito grtwt b ias Kitted ie to: Kilted M DM to to? SUM SmpUob te yuhBOBMT MJcroaeopU Evkdeaee of paaesioeotjtcaU Draj* Ked____ Oaow DvAUf nar? AMou Urii OtHoter laSHcsasa Foeal XMfluaa DeraoeratJao Hr' He* alars*Fffmnsa ISr* eroals tarot DeeeBerftOoB erotta Pneumonia FaaumenJn FootunoaU i , , 4 4+ fc 4 44 ,. 4 .. 444 444 44 4 4 444 f+ 444 44 4 -+ .. ,, 4 4*44 444 44 4+ 444 44 ,, .. .. 44 44 44 4 44' 44 44 44' 44 44 44 .. .* a ee A4 4A pulmonary ahacnan 91 444 44 -> 44 Pneumonia 444 44 444 Pneumonia a ee< 4 +44 444 44 444 444 444 44 4+4 4* t 4' .. 44 .. AA |+ 444 44 44 44 44 Pueumooia 4 44 IIh- - 4 444 44 4 44 44 .. 4 Sjttboti: 4, ](ghl kmUw; 44, taodarae* fraction; 4-t-f, adsoed wfleo. J 331 SCHEPBXS ET AL. air, the protective action of the gypsum is mais that died of natural causes, distinct pig withdrawn and the quartz particles then exert mentation had developed, and bronchiolitis of their usual harmful effort. T1* quartz and a moderate degree was in evidence, The latter gypsum also appear to have been carried to condition may have been linked with the the lymph nodes at a differential rate which pneumonk process, as bronchiolitis was less favored the hyalinuing action of the quartz common attd less marked in those animals at these sites. which were killed for sampling (Table 11). S. EXPOSURE TO A MIXTURE OF TWO PARTS OF CAtCINED GVPSUM DUST AND ONE FAST OP tfUARTE DUST Focal cellular proliferation due to dust could be discerned from about the IOth month onward, and diffuse cellular infiltrations com Since the experiment with a mixture of menced to appear after the 14th month. How equal parts of quartz dust and caJdned gyp ever, except in isolated cases, collagen deposi sum dust gave definite evidence of an early tion, hyalimzation, and necrosis rarely were protective action of the gypsum, the observa observed. Such degenerative changes were tions were checked by conducting another ex slightly commoner and wore advanced m periment in which a mixture of 2 parts (by those animals that had died of pneumonia. volume) of the gypsum to 1 part of the The hilar lymph nodes likewise underwent quartz' was used. It was found that on a enlargement, mainly from cellular prolifera weight basis the ratio was closer to 2)4:1. tion, with but moderate and considerably de In the experiment with the 2:1 mixture, 64 layed fibrous changes and necrosis in isolated guinea pigs were exposed for periods up to instances only. 29 months, and the average dust concentra tion was 245,000,000 particles per cubic foot of air. As in the preceding experiment, the actual aerosol in the animal cages differed in composition from the hopper mixture, tl* It appears then that when the amount of quartz dust to which the animals were ex posed simultaneously with the calcined gyp sum dust was reduced to about one-third the level introduced in the preceding experiment ratio of calcined gypsum to quarts in the the fibrogenic and necrotizing influences of aerosol being approximately 3:1 (Table 9). the quartz dust were materially inhibited Tabls 9.--Competition of Aerosol and of Settled Dust in Comparison teitk Parent Hopper Mixture Composed of Two Volumes of Calcined Gypsum Dust and One Vol ume of Quartz Dust All Samples Were Dried at 100 C Before Analysis despite prolonged exposure. Perhaps degen erative changes might have ensued, as in the previous experiment, had the dusting been discontinued. To show that the animals had actually trapped quartz dust in their pulmonary tis sues, the lungs of guinea pigs exposed to dust Sopper Conpooom MIx'urv, Per Ceat 6KH ...................... E< CaSO. ...................... tit Settled Ehwt on Top of Oa* F/ Out SM to.* Aeresel tastd* Cues, Fcr Ceal 17.? 6*.l of the gypsum-quartz mixture and to quartz dust alone were analyzed for their silica content. The results obtained for the gyp sum-quartz-exposed animals are contrasted Sico. S............. * M with the findings ior the quartz control series FeiOe. AhO* ........... , XjftttUoe ................ Tot*l................... C-6 OS j 0.1 9.3 i A# 4 moz (Table 12). It will be observed that, although considerably less dust was retained in the lungs of the gypsum-quartz animals than was trapped in the tissues of the control animals, Of the 64 guinea pigs, 42% died of respi sufficient quartz accumulated in the lungs t<- ratory disease, in most cases of chronic pneu have had some fibrogenic influence. It should monia. These deaths were, however, evenlv be noted, however, that at the 24th month distributed over the full 29 month period and there was but little more quartz in the lung may therefore be of reduced statistical sig ash of the animals exposed to the mixed dust nificance (Table 10). In the majority of anl< than there was at 8 months. At the 22-month 332 BIOLOGICAL EFFECT OF CALCINED GYPSUM DUST Table 10.--Combined Biolegieai Action of Cabined Cyfrum Dust and Quarts Dust Guinea. Pigs Were Exposed fey Inhalation to an Aerosol Derived iron a Mixture of Two Volumes of Calcined Gypsum Dau &d One Volume of Quartz Dust; Exposure Was Continuous Uatil Death Tabulation of Animals Which Died of Pneumonia or Other Natural Cause Daring Course of Exposure xpo. fQN Qstoea (o PI*. feuat. No. iHtt HS Si Can* of Deatb PscvnioBl* * m PneutoooM ST w TaberroloB# (1 82S s t CtlTORk pneumonia Cftrottle pneumonia ss 576 Cbrente pMumoel* 66 m Cferente pneuiooblt es an pneumonia oca (%m!o pneumonia u 0 Cbrente pBCOEBOfila as ill Obrente {)I(ODO&ll S3 *2* Obrente poetuBonit 51 04 tt OS Obrente ponuatonln Cbrenle paeusionJa 43 OT C&roote pneumonia 28 *17 Obreofe powmonf* 19 <a Ohfonle pMUBroots ei <30 Cferenie pwttarealn se <S Ctorente pneumonia u 09 Cbrente JMteOBMQlB 01 m Cbrente pneumonia AS tto Abnreet u ess CUo&lt pneumonia < *83 AMcass a 87 At*CBU >8 610 CfcToalt pneumonia it 1 Cfero&k pneumonia Um f r..-- aoa MfcJ-eopte StUom*of Pamooeoatoel* eftioInto CtUotef IniHrmiJoB DnjrawreUoa AMte* ' fell' Bra- N- ' Uh Poew Suae PTbroBi ism erelie , << 4 .. 444 44 4 4 - 44 4 44 -4 44 44 4 + +4' 4 -> 4 * -- 44 44 -* 4 - 4 *- 44 4-4 > 4 - 4-4 44 4-4 4 4 4 *- < +-4 44 +4- 44 -44- 44 4 4 4 4 4 4 * ** 4 44 < 44 44 -- 4 - * 44 44 44 44 44 44 44 44 - 4 - 444 * 444 44 44 44 44 4 - 444 44 44 44 44 44 44 44 44 44 H-+ 44 44 4 44 4 44 444 44 .. .. 44 44 44 4 444 4 444 4 +44 4 -> 4 Seaeoca t PabBnoerr StpOHlRtB H?a- NoBMfit Pl&reo* &* ereUe 4 444 44 > ,, .. 444 - * 44 444 - 44 4+ 44 44 44 44 .. 44 *' *- /< 44 44 .. * ** ** 44 44 44 44 *4 44 44 44 44 44 - 4 44 * 44 * * 44 44 ** ** -* ** - 4,, 4 - .. .. 44 44 44 44 44 - ' - 44 Rrmbou: 4. reaction; 44. tsodsmW reMUOB; >.f.f, #>*Beod reactleo. i period tl animals which had breathed quartz . dust only had nearly three times as much 6. EXPOSURE TO CALCINED GYPSUM feUST. TUSH INFECTION WITH TUBERCLE BACILLI, AND IER CONTINUATION OF THE DUST SiO* in their lung ash as had the animals exposed to the mixed gypsum and quartz dust for the same period. We. may, therefore, not be dealing after all with any specific ' inhibiting action against the effect of quart2 T EXPOSURE 08 REMOVAL TO NORMAL AIR In fhis experiment, which was divided into two j&rts, the effect of inhaled calcined gyp sum ihist on a tuberculous infection was * dust on tissue but merely with a reduction or studied. Jn Ow first part, 20guinea pigs, after dilution of the quartz component. tiavinjs been exposed to the dust for 6 months < 333 i SCHEPERS ET AU 1aju li.--Piologiu# Action of CeJaned Gypsum Dust and Quarts Dust Gotoe Pip Exposed by JohaJation to an Aerosol Derived from a Mixture of Two Volumes of CftloDcd Gypsom Dusi awl Owe Volume Quonx Study of Animals Killed for Sampling GuAc* nr. Me. 464fc J,* K* *,0,43, 10 11,22. u, if, is, ts n.a.w.tt o,taas.w It. 40.0 EM* mre to Dot, or* s* u* apt R& 401 * 4m U6 m no STB Xtwowepk S'&nctei Pwiftacw>WU Bcsetice te Pnlaootr? _________ LyagXo^w rvaufcu PtrOMB. Bfoaaii-/ urioa etfik >Ml --.. .--| 4 + .. 44 -4 + +4+4 4+ 4+4 +4 4+4 44-4 4 4 4 4 + 4 44 44 44 4 4 4 4 *4 44 44 44' 4+ 44 ,, 4 + 44 44 44 <44 44+ 4+4 44 + ,, 4 4 4 4 44 INI*--- , r XnceMiaOoD P*- X* Sahrrs- Bit US* crotfa Btet FIPwUc }oi ratte t, 99 .. +4 . +4 ,4 ,, + 44+ 4 + +4+ +4 4+4 4 + + ++4 4 4 + + +44 4 + + 4 444 ++ +4 < 4+4 +4 44 fijaibot*: 4. aitcM n(ioa; <*+, sjoOente n*etfeiu +4+, w*3oa: A, aieUctuta. were infected with attenuated Ri tubercle bacilli and thereafter immediately returned to the dust room for additional exposure, up to J8 months more. For the second part of the experiment, the preinfection period d exposure to the dust was longer, namely, 25 months instead of 6 months. After being in fected, the 25 animals used were not returned to the dust room. Instead, they were trans ferred to a normal environment and allowed to live there for periods as long as 18 months. As a control experiment, 12 guinea pigs were infected by R* bacilli but were not ex posed to dust. The results of these studies are summarized in Tables 13 and 14, Before the influence of inhaled cakined gypsum dust or quart* dust on the course of experimental tuberculosis can be interpreted, the effect of Rj tubeide bacilli on the guinea pig Sung should be briefly reviewed (Table 15). It will be noted that, erf the 12 animals in the control experiment (Tabic 15), 6 died within a 22-month period of observation. In all cases the deaths were due to pulmonary causes, and in at least one instance the cause was spreading cavitary tuberculosis* How ever, only in this one case was there spread ing tuberculosis, in all other instances there were either no signs of tuberculosis or but one to three small tubercles. In only four instances did these tubercles show any activ ity, Tuberculosis was detectable in the pul monary lymph nodes in one instance, but it Table 12.--Ask end Sittia Content of Lungs of Guinea Pigs After Exposure to Aerosols Composed, Respeetevety, of Calcined Gypsum Dost and Quarts Dust *** a Rotio of 2:i ani of Quarts Zhtsi Alone srsr-T.'i ,vff.v:.r ,igrass Grpftim: Qutm centr&i XrvosuR. Ho. 6 n 18 18 $6 >7 IMS n St Ouinoa i.s 6,4,6 t.s 9 n, is,is if. is, ss ea.sr 88, 28, SOSes ` 4s,%of * %0t 1 3Were owe Lour %o/ JUh 7as 2* 17.CS OK IS4* .? 0.70 1l4f ?as e 90T 0.83 Sfl.47 sit 0.76 16.18 ,, 6.14 0.7! 2l*t 6.6S IM isyr ' Pi*, Ko. 2 u, 78,67 7 *,t* 64 B, SB ~S0kt A*, *.n7 D/ieO Lui* ' Prie%doX\osa 9& .n lift *31 1201 ua nas tat Bid Ste HX82 tag 071 8.(2 . tas s+s 4SJS 46.77 41.78 B.7ft ss.to 88.(1 smb 334 BIOLOGICAL EFFECT OF CALCINED GYPSUM DVS1' Table 1$<~~Infiuemr of Cofcmed Gypsum Dial on Ike Coarse of Experimental Tubereulosie Cube* Pig* Wert Exposed by Inhalation to Calcined Gypsum Dust for Six Months, Were Than infected with R( Tebcfde Badlti, and Were Immediately Returned to the Dust Room foe Centkwaticn of Tbtif Exposure to Dust Until Death vBivuar-} Altar Isto* S? Uob, MSK r u 17 3S 89 *8 9 U 98 u n *i 78 12 91 IS* . SB 1M SB 898 858 875 m 901 886 189 M m 489 8S too sso m m (61 SW 7tU 1> s K I> s s X D D 8 !> D X s X s> K E TuVccufoeis CSUS* of De<* pKwmoolv FmuujosJ* Bated * u Tubenulotts t Pewmonto J Poatenf FTtfUlflOBlS 4 4+4 +, 4+4 ++ 444 444 +4 + +++ 444 .......... 4+ 44 Caleifi* mins TSBrolU 44 44 4+ > 4 44 + ++ ,, ++ 4+ 4 +4 .. ++ .. .. ,, 44 + 4+ .. 0+ +4 + -4' 4 4 ,, .. +4 .. 4+ t * 44 4-H* * V 44 444 4 4 > Cues. Boa 4 4 ,, 4 4 ,, .. 4 4 ,, 4 Cavil? 444 TSjiwiG. aarr tymM Nodes Lttf 04 *444 *+ ST+ *44 *4 *4 *+ *44+ 044 Spites *444 eoeeo 044 FT 44 ST+4 *T+4 FT ,, FI+4 rew *44 *CT .......... <uo> K+44 *T4 *4+ fX+ ...... *4 *4 ...... rx+ 4444 B* rs4 a* BF FT -* .......... *T ' 8frr1>ol: C,*ve>ttoc; T, flferovtt; TS, fibrous aodufa*; IT, fibroin twbvmOoaM; J?CT, fiorotawoog tabereuloals; HPP, bxsta* %**; K, aaeimts: *, r**St* 44.8BO0*4'* natOtia: | t r( edraanO navlioD. was inactive. 3n the guinea pig with spread ing pulmonary tuberculosis, active tuber culosis could be found not only in the hilar nodes but also in the spleen and liver. When the guinea pigs in one of the dusted groups (Table 33) had been exposed to calcined gypsum dust for 6 months, infected, and then further exposed to the gypsum dust for an additional 18 months, only 9 of the 20 animals died spontaneously. Of these deaths, only six were ascribed to pulmonary causes. While signs of healing were in evidence in TaSlb 34,--Influence of Calcined GyPsun* Duel on ike Course of Experimental Tul/erculosie Guinea Pi#fs Were Exposed by Inhalation to Calcined Gypsum Past for Twenty-Five Months, Infected with R* Tubercle Bacilli, and Transferred to Normal Air OutMS Fir. Vo. G&S-W as 87 84 . 85 8? (S 8 m e 8 8 8 VX> Botvtoel telloe. Den 8 10 8 ! IS 105 m M Ui e tee * Ul Ml Fsle led Dted KVttet Sled SilkC Kitted Steed Etifed Ste*J EIQed KGIefi %vm EJUed Killert Silted Cause of Eesta PnraaooJe I'aeumoela Fueledosie << M ...... -........... .. Puk&ofisrr TubereuToHe Oektfl* fufeereies tsUoti Ffbrasfe Spf*ad 99 8 t> 4 4. 9 ,, 14 85 44 <4 17 44 ;+ to 44 tf+ l4 9 e4 4 44 t- i ,, .. 8+ S 4 4+ 1, IS .. 4+ DlaaatDtBfttioo ClHt. Uoo yulraa. asr? tVBrt* Vodw ,, u.er fipita ,, ,, ,, 44 ,, Of C++ FT4 *4 .. .. Of 04 ,, ,, 44 .. *4 *4 .. ,, 4 SaiEPERS ET A/.. Tablr 15.--Fait of Guinea Pigs Infected with R> Tubercle Bacilli Control Study: No Dost Exposure Gstaea IMmril, Rs,* Dst fits.12 s 11 (6 tm l e as a SAS t 4 e *46 u> fit* t IM s (M Fate Died Died DSM DM K31M SUM DM XflSM DIM SUM SIUM S1BM Cauae of Dealt) nUieMUT Ififaret Pceorooflia Acute eoewestlon PimrauBla eeee 1 Fulaiesarr abeeeas 1^* TUbarcoIoitt PuknMsry TUBcfcuteak DMocSaaud Tutaroteifa A7rated Tntavfea Caaeation 1 ++ i 40+ 1 l w Coeflueat Fetmooery Tobereu. Lyaip* toils Mode 4, . , 4 Urw + Spteea .. t (?) 8 t (?) 1 (?) +++ 4 +++ . 4-4+ +-H- Brmbels: f, alight weetloB; 4-*-, aoderata reaetloa; 4-44-. adeaaecJ reaction. most instances, in a few cases with asso ciated calcification, spreads occurred in six instances; two cases developed cavitary tuberculosis and one died from this disease. Fibrosis was a prominent feature in a major ity of instances, but caseation persisted in eight cases. Tl* tuberculous process had, however, spread to the pulmonary lymph nodes, liver, and spleen but in most instances was partly healed. Caseation occurred in iso lated instances, and fibrocaseous tuberculosis in one case. There was a higher proportion 0} nodules in the animals surviving longer, and in these there was also associated hyaline fibrosis. The occurrence of 34Jo spreads in the gypsum-dusted guinea pigs indicates a dis tinct excess over that which occurred in the control series (8.3fo). However, it should be recalled that the control group was rela tively small. Added to this tendency to spread, there were in the dusted animals the signs of caseation, cavitation and fibrosis, and metastatic dissemination to the hilar nodes and abdominal organs. All these changes in dicate some stimulatory effect of the calcined gypsum dust on the tuberculous process. There was no indication, however, that the tuberculosis promoted any pneumoconiotic process. When the infection by means of the R% tubercle bacilli was initiated at the end of a 25-month period of exposure to the caldned gypsum dust (Table 14), the influence of Table 16.--Influence of Calcined Gypsum and Quarts Dust on the Course of Experimental Tuberculosis Guinea Pigg Were Exposed by Inhalation \o Calcined Gypsum Dust for Three Weeks and Thereafter Alternately fo Quart* Dust and to Calcined Gypsum Dust for a Week at a Time; After 371 Days Pigs Were Infected with R< Tubercle Bacilli, and Then Altercating Dust Exposure Continued Survive! Alter toGulcet tnetteu. PJg.Ho. Dare 4*24 JOT e SSf, 1 8a Faie IUM SIUM 1MM 8 sss SUM a *08 KfOM Cease cl Dee Tobweuloafs pcaUTCOBla Pufa^ooary TUDareuteMi Spread +++ 4-H- 4' TuUrcute- Oakifl* Cavlt? HlteosJe cation 4-4-f + + 4-4-+ 4- 4- +4-+ + + 4-4-4- -+ Dtueolsetteo FMaooarr Lyopfi Jfodtfl * tori* SCkoile ++ 4-4- .. + +4 4+ Uw TB+. T+ +++ 4-++ +++ 4-4-+ r+-f X4-4- SpfeMS B++ Brrehots: TS. toLeteuloilhcosIs: T, fubemstede; S, *JUpo*I: 4, sltgtt rnetloc; 4-h moment* advanced reaction. 336 4-+4-. t-t-t. i f I I the dust on the course of the infection was entirely benign. But 3 of the 15 animals died of pneumonia within the firs month after infection and none thereafter. Mild spreads In the second part of this experiment, 21 guinea pigs were infected with Hi tubercle bacilli after 3 months of exposure to an aero sol derived from a mixture of equal parts of were found in six of the animals killed before calcined gypsum and quartz, the dusting pro* the sixth month and none in the later stages. cedure being continued for 27 months after Caseation was found twice only in the lungs and twice also in pulmonary lymph nodes. Pulmonary fibrosis was quite common in the healing tubercles. No pneumoconiosis oc curred. the infection was initiated. Half of the ani mals died from pneumonia during this pro tracted period, the spontaneous deaths oc curring slightly more frequently toward the end of the experiment (Tabic 17). This study therefore indicates tliat the prior two-year period of inhalation of calcined gyp sum dust modified the native susceptibility of the guinea pigs to the R* tubercle bacillus adversely, though not materially so. The localisation of the lesions was affected, and for their normal tendency to heal by resolu tion there was substituted a process of healing by fibrosis, with calcification in a few in stances. Signs of pneumoconiosis were slow to de velop, but from the I3th month after infection {16 months from the start of the dusting) marked and diffuse cellular infiltration super vened, with hyaline changes in many of these lungs. Pulmonary tuberculosis of a confluent type and of moderate extent made an early appearance and persisted throughout the long period ot the study. Caseation, cavitation, or calcification, however, was limited to isolated 7. ALTERNATE WEEKLY" EXPOSURES TO CALCSNKD GYPSUM DUST AND TO UUARTZ DUST AND INFECTION WITH Bj TUBERCLE BACILLI In the first part of the third phase of the infection experiment, five guinea pigs were exposed alternately to quartz dust and to calcined gypsum dust for weekly sessions after a preliminary course of gypsum in halation for three weeks. At the end of about 6 months they were infected with Rt tubercle instances, especially in the latter months of the study. The pulmonary lymph nodes showed, an early tendency toward fibrosis and tubercutosilicosis. Necrosis became a rather constant finding at a later stage. Necrotic fod occurred also in the liver, occasionally with tubercu losis. Rather more commonly, tuberculous metastases were found is the spleen, and in a number of cases tuberculosilicosis likewise bacilli, and the alternating quartz-and-gyp- occurred in that organ. sum regimen was continued for an additional period of 13# months. The results of this study are summarized in Table 16. Spreading and cavitary tuberculosis was rapidly induced in three specimens within the first year after infection, while tuberculosilicosis within the pulmonary tissues dominated the scene, particularly in the later phases of the study. Foci of tuberculosis could be discerned in the liver, and silicotic nodules occurred in the hilar lymph nodes in all cases and once in the spleen. These results and their relatively prompt occurrence leave no doubt that alternating .gypsum and quaru exposures influence the Once more, therefore, the concurrent ex posure to quartz dust and calcined gypsurn dust in equal proportions proinotes the de velopment of tuberculosis in the infected guinea pigs. However, the disease does not reach a destructive and fatal stage like that seen when the dust exposure is to quartz dust alone (Table 4), It will be observed from this record that exposure fo quartz dust con verts the infection with Rj tubercle bacilli into a-spreading tuberculous process asso ciated with tuberculosilicosis and a high and early mortality rate. 3 COMMENT course of tuberculosis adversely. The result is greatly modified, however, by the degree to which silicosis develops concurrently. Since in previous experiments the infraper itoneal injection of even an excessive quan tity of calcined gypsum particles did not pro* ' 33? SCHBPERS ET AL. ?4iu 17*--Influence of ColcxUtd Gyfisum Dust end Quarts Dust on the Course of EjtforinenUit Tubtrevtosi* Gtaoea Pigs Were Exposed bj lohalatioa for Three Monfhs to an Aerosol Derived from a Mixture of VohKives 0$ CaSeaneti Qypsom Pst and Quart* Duet and Were Then Infected with & Tubercle Bacilli; After Infection the Animals Were Intnediaiely Returned to the I>ntt Room Where Their Dust Exposure Was Continued Until Death gurrti) Atur GufMH larte Pie. Uon. Ho. Dan F.te tffrS JTS 17 m n rrt E B 14 at D a &$ t sss a as E E D is tea s tea E 10 4K K 9 its a tas wm KB K D D E a' 510 D V St9 u 1i 870 e ns 4M ID 803 23 X> E V B t> Oaue oi Xtakt& Pstontui FeeunsanJ* Pmboodu PoeaaoBi* PoamoBj* PneoafcOAJa Paeunoala FSMBStOOd* Paeuaigale FBeaaeaia PubBoaer? ToJ*reu>ett BtucmlaaltOA Coo. Ouw Suec U0Q fijalitw HeeracJe 4 44 +++ 444 + 444 444 ch 4 0L4- 4 4 4,, 4 4 4 4 4-f+ 4 +4 H 44 44 4-HH 44 4-H444 4-H fH 4-H- 4 4-H OI4 <0444 OAH 0144 H .. OAH H4 H OH- 4 H H -Hr 44 4-H-H- 4-H- 4-,,H ,, tw 4 44 - ,, 4 Fatal 444 44 H 44 .. " ,, 4 .. meuM , , kt 4 444 44, 4 444 44 4+ 444 4-H 444 44+ 44+ Pulesse7 l.jnijrt t*otfe PH TF+ ST4 8TH 8TH + N++ + F+4 S+4 HH H4 H+ K+ H4 P++ K+4 JJm ,, F> 4 H4 ,, T-t- ,, *4 H4 *1+ T4 H4 *4 T+ BpMB 14 . rr+ F4 F+ T+ + TF+ TT4 CT+ TF4 W* T+ T+ Sjabott: *. earn nseUou; 4*+ tooflerete retettoa; 4-H. Mtm* iwMiaa; cs, etvjuflea: CL esfctftcatxa; r, SMosta; B, K, Mcrefis; 8T, sQfeosobamtMa: T. eataietfeak; TF, tobwwfco* abraek duce progressive fibrosis, it was anticipated that the inhalation of those particles would have bo serious effect upon the fangs. That assumption has been verified by the studies reported in this paper. It has been demon strated that the small increments of fine cal cined gypsum particles inhaled into the lungs largely disappear, apparently as a result of solution in the tissues. Very little anatomic evidence of their presence can be discovered. Evidences of reaction in the fixed tissues of the lung are, minimal, even after exposures to high concentrations for a period of two years. In the hilar lymph nodes, which must have received the greater part of the gypsum that was spirited away ffom the lung parenchyma in this series of guinea pigs, there is an almost specific pattern of reaction comprising medul lary hyperplasia in the nodes and their fol licles which is unaccompanied by any increase its the lymphoid tissue. Fibrosis was, however, conspicuous by its absence. It is to be hoped that this interesting find* iflg may mean that it would be inconceivable that the inhalation of calcined gypsum dust will produce significant reactions in otherwise healthy lungs of industrial personnel, perhaps even regardless of atmospheric concentra tions, This circumstance would therefore con clusively eliminate calcined gypsum per sc as the cause of the pulmonary lesions which have already been reported in respect of deceased gypsum-industry employes, It is difficult to evaluate the high pneu monia rate in these guinea pigs. By compari son with other studies conducted in The Saranac Laboratory, it is excessive (Tabic 18). However, these latter investigations have been conducted in more recent yea/s when it has been possible to control epizootics more effectively by ultraviolet-Ught radiation 338 j BIOLOGICAL EFFECT OF CALCINED GYPSUM DUST Ta%is it.--Comparison of Number el Spontaneous Destks of Guinea Figs m Inhalation Experiments with Various Dusts Several possible explanations for this con dition should be entertained. The first con cerns the possibility of chemical or physical interaction between the gypsum and the Dado! But 3a*ru ................... . SfiiM tea*............ ... Aaor^oet Site* a...... AnwW>" BDk B....... Ajootj&hs SBko O...... Asorpbou gate* t>.......... Vfe*sfe ilui................ finevd toftut. Kv. a 192 2E* 83 U Foofltf Pe*d.*o< * 4 U 04 0 MortoflH Bow (VOttt 0 th !C tt a u % quartz, cither in the hopper mixture or even after deposition in the guinea pig tissues. Next should be considered the factor of bio logical antagonism ia quarts, which may be induced by the gypsum. To these observa tions should be added the fact that the dose of quartz was actually decreased through dilu tion with the gypsum and that the quartz was and antibiotics. Perhaps bo further attention administered to older guinea pigs and to the need be given to the matter. However, the hardiest survivors of earlier phases of the high pneumonia rates and the emphasis of experiment. It is even possible, though un this phenomenon on certain phases of the likely, that the quartz dust itself may have study suggest that the matter is at least worth "aged" with the passage of time, thus not further investigation. being quite as potent as at earlier phases of The experiments demonstrated that guinea the experiment ' pigs are protected against ordinarily danger The latter question cannot receive an ous concentrations of quartz dust by the con answer until we have more information con current presence of calcined gypsum dust in cerning the influence of aging of powdered the same atmosphere. Under the conditions quartz on its biological properties. The prob of the experiments, in which the ratio of lem whether quartz has a greater or a Jess quartz to gypsum was relatively high, the propensity for damaging the tissues of older protection was not absolute or uniform for laboratory animals compared with its effects all tbc exposed animals. The protective action or die younger specimens usually selected lor of the calcined gypsum completely prevented study has sever been properly examined, the development of fibrosis in the majority of linked with this question is the possibility cases and retarded or modified the character that mere survival against all the forces which of the dust reaction in the remainder. The naturally or artificially may tend to decimate degree of protection was not defined wholly the ranks of laboratory animals may signify by the length of exposure but was affected to a hardy stock perhaps also more resistant to some extent by other factors not dearly quartz dust There is no answer to this, but understood. Sporadic cases of nodular fibrosis it should be entertained as one of the possible devtloped in some, animals exposed for mechanisms which influenced the results in shorter periods than in other animals which this investigation. failed to manifest this type of reaction. Pos The fact that the quartz dose was actually sibly host factors involving individual suscep decreased through dilution may have rele tibility were involved. vance. >Over the years, experiments with The protection was most evident in respect quartzidust have been carried out in The to the degree to which the prevalence or Saranac Laboratory in a great diversity of severity of bronchiolitis was reduced in the animals exposed to both gypsum and quartz; to the retardation of the pulmonary cellular reaction and the diminution of its extent; to dosagelevels. Except in extreme ranges of particle* concentration, the tissue reaction to quartz Jdoes not vary too obviously. To be precise) however, no systematic body of tiie limited amount of fibrosis, hyahnizarion, knowledge exists to enable one to make com or necrosis which ensued, and to the inhibi parisons with complete assurance, The great tion of dissemination of the dust to abdominal differences observed in the present series of organs and even to the regional lymph nodes. experiments suggest decidedly that the ex- 33? i SCHEPF.RS ST AL Tasxjz \9<--Effect of f'arymff the Amount of Gyfsum ok the SoiMSty oi paniculate Quart* Suspended in a Buffer Solution Quartz Particle Si: 1m to 3m Buffer Solution: H*BO*->aOH pH 6.90 Incubation: 37 C for Twenty Hour* Qypsva ttoipeasJes, Satubie BSOi, M. 0 9M SO a.TO 60 US. 9JQ * 1M no ifiOO tJt ias ton UO a/so 6/0) l* MO CeeVvJ: BUarU S/CO 0,12 t&ercweiB Setuota ttOi, *erOcat S34 soft 02.< 128.5 UTfl It** ju.r uea 1UJ pHatltea to Hi. .5s .* ear 7/a 7/S 7/D planatbn docs not rest merely with the ques tion of dilution. In The Saranac Laboratory, experience has also been gained with dilution as a factor in relation to "inert'' substances, such as iron oxide, and the results of these studies serve as further confirmation that die inhibition achieved by the calcined gypsum dust is real and not merely a function of quartz dosage. That the quartz dust actually did enter into the lung tissues in a dosage ratio bearing some relation to that according to which it was administered was adequately shown by the chemical analyses of guinea pig Jungs recorded in Table 12. That the influence of the gypsum on ti* quartz may have been due to some form of physicochemical interaction is suggested by Tafcfcs 19 and 20 and the known fact that gypsum particles have a positive electrical charge while the charge of quartz particles is negative. In Table 19 it is shown that the presence of gypsum in a buffered solution increases the solubility of suspended quartz particles considerably without substantially changing tlte pH, Table 20 confirms.the latter observation and shows that the presence of gypsum raises the pH of the solution mark edly when 1 % gypsum and 1 % quartz arc incubated together in a buffered solution at 37 C for 24 hours. If the theory of Holt* that silica exerts its necrotizing and fibrogentc action by virtue of silicic acid polymer's which can form only is as add pH range, be acceptable, the reduction in the influence of die quartz in the presence of gypsum may find an explanation. Such a chemical theory receives further confirmation from the obser. v&tion jfcat when quartz and gypsum were administered in alternating weekly doses the resultant pneumoconiosis was much worse than when an equivalent amount of calcined gypsum dust was introduced into the guinea pig lungs simultaneously with the quartz dust. Owing to the apparently rapid elimina tion of the gypsum and the tardiness with which koniophores make an appearance in response to its introduction, this would mean perhaps that in the alternating exposure ex periment the gypsum had practically been eliminated at the end oi each week end, so that the quartz had an unimpeded oppor tunity to act on tiie tissues in focal and later diffuse regions where a low pH prevailed. The elimination experiment in which the ani mals were left in fresh air after a prolonged period of exposure to quartz dust and calcined gypsum dust also indicates the same chemical explanation. By the progressive loss of gyp sum from the lungs, the local tissue pH could have been progressively reduced, thus liber ating the full action of the accumulated quartz. The answer to these enigmata can come only through further research. Tliat the total result may have been simply one of biologically antagonistic effects of gypsum and quartz and even perhaps merely Tasui 20Effect of Varying fff Values on the Solubility of Particulolt Quart* When Sus pended toith Calcined Cyfmm in a Buffer Solution Quartz Particle Size: 1m to 3m Barter Solution: H*BOr-NaOH Intubation: 37 C for Twenty-Four Hours ---- ........ ...................................... mmt Sue.r SeV tk-a. pH tf.f 1A as it) 10.5 Suioessloa HSQo*?t* + OfcOjrjwusa SuspeazfoB + 1% Gypoua betubte SJO., pHAter Horace. Wfir. I/O <Mt O.M 604 US 1.15 a.es os* 14* S50 9 It flotohh 8fOi, HZ/KOOe. i.ss 1J6 156 til no i.ii nHAtUr war. 800 r nn 5 SO MQ BIOLOGICAL EFFECT OF CALCINED GYPSUM DUST a matter of tissueor cellular competition can- A fioaljxwot of direct practical application nofcbe dismissed-as a possibility-without due might be stressed*here] namely, that where a consKferarioc.The paucity of ttoniotfhores in series 6S pt&nQ&ry reaeSbos tonitiU when the: gypsum-drenched* long ntty mean noV calcined gypsum and quartz are administered only'that ealdaed gypsum does not exert a either together (successively^ simultaneously, chemotropism Cor these tells, such as quartz or altematingly) or in conjunction with a exerts markedly,** but even that the presence tuberculous infection, the final histopatho- of gypsum repels these cells. Silicosis does logtcal result achieved is not a mere quanti not-'ensue until quartz particles have been tative expression of the relative component phagocytes*! by the sh^oisr tri&erophag&s action of each of these three etiol$g3caJ agents and transported to sites where their cumula but actually, in a sense, is a new type of lesion, tive action can provoke local lesions. If gyp a form of holistic synthesis. This is the prob sum blocks the approach of these cells, the lem of the mixed pneumoconioses which are quartz particles will amply not be picked up. being encountered in increasing numbers in It Is possible too that the absence of alveo industry today. Their precise nature cannot lar `Toacxophages in the: tarly phase of the be simply predicted by reference to the known exposure to xafanerf gypsum dust may sig properties of the separate component mineral nify merely:that they do not need to enter substances. More research is needed about the ;alvedi te ingest the gypsum. The latter, all these (natters, * 1 *- being somewhat soluble, could be:picked up afteipenetration of the alveolar.walls, As the' gypsum .is; not likely , to prove immediately SVMMAXV Xo*s*series ofloogHemiThth^feti^^p^rl' toxk to'tbe macrophagesrtheretwould be do ments.-guinea pigswere expo&ed t6 calcined barrier to their transportation totftscsrnt parts gypsum dbst^lonc and to mixtures of quanz and-disappearance from the lungs. In such dust and calcined gypsum dust; in addition, circumstances they would not be available to the influence of the gypsum and of the gyp pick up the quartz particles. ' Xhcinflaence of flocculation on the accessi bility of the'quartz should also be examined It was shown by Gardner 4 that when calcined gypsum dust* and quarts dust are'Suspended in tdust ronm simultaneously there is a sum mixed with quartz on the' cdurse of ex perimental tuberculosis wu studied. The effect of calcined gypsum dust on the lungs of guinea pigs exposed to the dust lor twoyears was too insignificant tobe classified as a pneumoconiosis, ' : :- marked tendency to flocculation.' Gardner The presence of calcined 'gypsum dust in sitspetXtd that this ought prevent the actual atmospheric suspensions with quartz dust inhalation of many of the suspended pirticles. offered to exposed guinea pigs a substantial However, his tabulation shows' that more degree of protection against the usual harm tharf SZfy of`the Clumps measured less than ful effects of the quartz dust. The protection, 5fk in diameter. These would be. respirable. however, was text when the exposures ceased, What was m, settled was whether these enabling the gypsum to-be removed from the clunlpsiof-particles remained-as aggregates lung tissue and liberatingthe-ffluffed of the even: within the ce&s of the; lung as lymph accumulated quartzsu;' b"' ^ ' nodes, The inhalation of <Caknfed gypsum dust Biologits! antagonism naturally goes fur- alone influenced the Cdtrtse of experimental ther5 than these simple mechanistic specula tuberculous infectionin guinea pigs-to a mod tions. Until we know more about all-these erately/dfsadvaneageoas degree only, mamissues; we must keep an open mind abont the fested chiefly by interfertnce'with thi process possible antagonistic influences and even; per of healing after initial Spread of the infection, haps, specific synergic? between calcined Thejcourse of a tuberculous process in gypsum end quartz in terms of tissue and guinea{pigs infected with Rj tubercle bacilli cellular enzyme and energy transfer systems. was adversely affected to a slighter degree '' 341 t SCHEPERS ET Al~ by exposure to a mixture of quartz dust and calcined gypsum dust than by exposure to quartz dust alone. Chemical analysis of lung tissues of guinea pigs that had been exposed to a mixture of quartz dust and calcined gypsum dust shows that the quartz is actually retained in the lung tissue but m less than half the concentration which may be achieved whto the exposure has been to quartz dust only. The .most likely explanation for the in hibitory effect of calcined gypsum on quarts appears to be in the realm of physical chem istry, though biochemical factors and blogicpl antagonism have not bees excluded. Acknowledgement Is made to Stanislaw P. Ka&zer, M LL, Biostatistidan, for tabulating and analyzing the data iron) which Table IS was construct'd REFERENCES l/Aamut Report of Tbe Saranac Laboratory-- 1933, 1934, 1935, 1936, 1939. *2. Third Symposium on Silicosis: Transcript of'the Third Silicosis Symposium held at The Saranac Laboratory June 21 to 25, 1937, 3. Fourth Symposium a Silicosis: Transcript ef the Fourth Silicosis Symposium held at The Saranac Laboratory June 19 to 23, 1939. 4. Silicosis and Asbestos!*, edited by A. J< 1 aura New York and London, Oxford University Tress, 1938, , 5. Gardner, L. D. >* History of the 3b Strain of Tubercle Badllus, Am. Rev. Tuberc. SS:$77, 1932. 4 Dowd, G. R.: Cultural Characteristics of the & Strain of Tubercle Bacillus with Particular Reference to Dissociation, Am. Rev. Tubers t2;$G, 1935. 7, Gardner, L. U., and Cumnungs, D. E.: Studies on Experimental Pnemnoaokofuosis: }V. liOvhdoo cl Asbestos Dust: 2is Effect span Pri mary Tuberculous Xnletrion, J, Indust. Hyg. t*:65, 1931. & Sehepers, G. W. H, and Darken, T. U.: Pathological Study of the Effects of Inhaled Gypsum Dust on Human Lnogs, A. M, A. Ardu ledust Health IS:209,1955. 9 Holt, P. P, and Yates, D. M.'. Studies on the Nature of Sflieosk: The Fobmerirataw of Sitkk Acad Sols to Vivo. Brit J. Exper. path. 15:52. 1954, 10, Schepcrs, G. W. H.: CytoUokjgical Uanifestations of the Surface Properties of Quartz, A. M. A. Arch. Indust Health 12:266-275, 1955, 342 i C*aidant Silicate *on minimal M Cayrifnatl Stodr tially hazardous raw mate C W. n SCH&m, MD, ftic T. M. &UMCAN, M.C. s4 . A. *..t*UBANT, Soraacc lake, H> Y. a product might not be to a nonhazardous form factoring process and, ,, -- appear to a greater or less extent in an unchanged condition in the final product. The day and ahak astd ia making cement often have a quartz content of 3)^ to 30% Gammerrial hydrous calcium silicate is ose or more, but chemical reactions, occurring _oftKe products that Ijave been stuped by when the raw mixture is heated, convert \lqr-terro tnhifatiori experiments at The practically all the hazardous frce-siiica .trac Sarafiac laboratory. These studies were ers! to a relatively harmless silicate. In most commenced in 1943 under the direction of samples of cement the amount of quartz that Dr. L. U.'Gardner and with the assistance of has come through the manufacturing process two of us <T. M. D. and A. B. D.) whocax- unchanged is less than 0.1%. \ --ried the work tt? its completion after Dr. ___ The hydrous caldutn silicate product used Gardner's death. Guinea pigs, rats, and ham* in The Saranac Laboratory riudids was made <ters were used, and the..experiments were fromi caldum hydroxide and^rilica^plaM designed to reveal the. nature of the pulmo moderate amount of*4Sfrs5s,>:v?fJch was nary tissue reaction to inhaled dust of the material in normal animals and in those har boring an experimentally induced tuberculous incorporated in tijafjnixture to impart cer tain desirable jdlystcai properties to the fin ished product Analysis of one sample of (fits infection. finished pkduct disclosed that approximately From experience with other siliceous 80$> pi the raw mixture had been converted materials one would expect to find that a hydrous caicism stifoafeand that about product composed only of calcium silicate y'iS% was magnesium silicate (Tabic i). would be relatively inert in its effect on tissue. Extensive clinical studies of industrial workers exposed to cement dust in lgh concentration have, for instance, shown that the effect of the inhaled dust of that material on the lungs is insignificant. Portland ceroem is composed principally of two cakjum sili cates. namely, dicalcium silicate and tri- About 1 % quarts persisted in the final prod uct. FVofeabb* the greater part of the mag nesium silicate was present as the fibrous mineral dsrysotile, although a portion may have beets ft* the form of serpentine, a min eral similar to chrysotile is chemical compo sition but tone which is nonfibrous. cakium silicate. Recognition iTiust be given, however, to the possibility that any poten- `Recorded for publication J5, 1955, Director. {Dr Scfrep*rs>. Associate Director (Mr. Dttrian), ao4 Research As^ja* <Mr. Dela- h*m), The Saranac Laboratory, EXPERIMENTAL METHOD ) To detersme the effect ol inhaled dust nf the product on^putrsonary tissue, an inhalation experi ment was ^conducted. In that experiment groups of guinea pigs, rats, and hamsters were exposed in a cubical fast room. S it. In dimension, in which ..............1..................... 343 SCHEPEKS ET Al- Table l.--Cemfesiti&i of Cemm^rdel Hydrous Calcium Situate OoaipeusBt ABsIrais *FrOrat p*o( AJtOi, no*..................... M.A .... OJS Oosaocad Aaalystj PerOiit <AP&W> Caktutt earbooau .............................- .. NafneUua sfBcsu ........................ 6 IS fetal .................. ...................... Total......................................... an atmospheric suspension of the hydrous eakium silicate prodoct was created by the action of a paddle which rotated inside a hopper cotiU&ng the material in finely divided form. The dust cloud generated ui this manner floated out Into the room where it was maintained far erght been <xt five dayA>i the week and for four hours on Saturdays Some of the animals were exposed to the dust for periods bj tong a* three years, Al regular intervals during the experiment a few anjmah were kitted, and the'organs examined grossly and micro seopkally to determine the nature and the extent of the tissue reaction to tl* calcium silicate product The tissue wax also analysed chemically to estimate the, amount of the inhaled <ht that was retained in the iuogs <4 animals exposed for detnite periods ofttime. Only guinea pigs were used in the studies dealing with infected animals. The Rj low-vlraleoce strain of tubercle badtli was introduced intra* Hracheally by means of ike utsufBatioa technique. Dust counts al atmospbenfcv,samlet collected in dsst room were made regufaMy by means ofthe midget impmger. The. ejneentratioc of the hydros* calcium silicate aeresol to *Wch the uninfected animals were exposed was general!? ^athfn the range of 100,000,000 to 12S.000.CRJD partides per cubic foot of air by light-field count, 4d the Over all average was i 15,000,000, In the MuS o to* fecled animals Ihe concentration was higfcr* the average bring 20S.0Q0.00O. EXPOSURE OP UK1KPECTED aJJIHALS Three species--guinea pig, rat, and ham ster---were employed in this phase of the investigation. Summaries of the findings are given in Tables 2,3, and 4. Attention should first be drawn to the relatively high mortality rate reflected in Table 2. That these deaths were due to mferetrrrefK epizootic infection was almost certain in the case of the guinea pigs and is emphasised the more forcefully by the fact that the animals died not only of pneumonia but also of pericarditis, peri tonitis, and cervical adenitis with abscess formation. That all the hamsters which died did so within the first year may also have some bearing cm the question. In the case of the rats, on the contrary, no animals died within the first year, and the rate at which animals succumbed increased with the pas sage of time. In view of the progressive nature of the pulmonary disease which en sued as a result of the exposure to the dust of the hydrous calcium silicate product, there h some presumptive evidence that the deaths and dust exposures bore some relation to each other in this instance. Table 2.--Biological Action of CommFei&l Hydrous CalcUtm Silicate Dust Cornea Pigs, Hamsters, and Rat* Were Exposed by Inhalation to an Aerosol of Commercial Hydrou* Calcium SlKcate post l/rrfif Death Record of Ammsh, Exposed to the Dost AJ0** Which Died Spontaneously &Met OelwaFI*................ . RausMr............................. jut.................................. ` lWmmoals ' j\ Sc. M* Cent R W-t 6 a?r 634 Csue* ofOetf<* FerttartJtU ^' No. Oeot 7 &. ... .. ... r*rft<5th aw' No. uA* 12 c ... ; .. I Cervical Adeem* tv/ *. Oeot t %* ... -> ... Total p ^ Xo. Cent TB 6 l?j .0 so . _&<5 dkO wiiisio first year et evpsrtstent. jma* dta wtfclfi first Tear of expert&nv Se% died vrlttaln first year of uswitmm. t To da* tbi from ocher eittan. SCHBPERS BT Al. The three species cl experimental ammate reacted somewhat differently to the dust, though the difference was more one of degree than ofquality. The most marked lesions were provoked in the guinea pigs, but this was probably largely due to the fact that dusting was carried on for a total of 36 months in the ease of this species, while the procedure was terminated at the end of the 18th month Jn the case of the rats and hamsters. When ^ cognizance is taken of this fact, it appears that, stage for stage, the Utter two animal groups actually suffered greater pulmonary damage sooner than did the guinea pigs. Thwdtfferenee is brought out by a compariL---sou of Tables 3 and 4, in the construction of which the same scales of values were used. Pigmentation of the pulmonary tissue or of pulmonary lymph nodes never became prominent features in these animals. It in creased diffusely as a light brows discolora tion which was most marked along the anterior margins of the lungs in the guinea pigs. As it became microscopically detectable at the 12th month of exposure only, its .absence in the case of the rats or hamsters before the )8ib month may have no true significance. It would seem that the pigment was almost entirely due to hemosiderin, as shown by Prussian blue staining. Pigmented koniophores and giant cells became a promi nent feature toward the terminal phase of the experiment on guinea pigs, and clusters of such cells could even be found in rat lungs where they were grouped around the smaller blood vessels. l.ymphoid hyperplasia was a prominent and persistent feature of the reaction in the guinea pigs. There was mild hyperplasia about the main bronchi in some of the rats, but this, was not an impressive observation for this .gpecies. No lymphoid hyperplasia was seen in the hamsters, The hyperplasia consisted almost entirely of lymphoid cell proliferation without any evidence of central macrophage accumulation such as may occur as a result of exposure to certain amorphous siliceous dusts. Mostly the lymph deposits remained spherical in shape and were thus well defined from sur- rounding structures. Occasionally, however, there was some lymphoid invasion of the walla of adjacent alveoli. At a later stage macrophages tended to accumulate around these lymph Fod. Is spite of this tendency toward intrapulmonary lymphoid hyperplasia, the pulmo nary lymph nodes showed no consistent corresponding change. In some of the an imate there was early lymphoid hyperplasia, bat in the majority the nodes enlarged slightly or moderately only at the start. After the animals had been in the dust atmosphere for two years, the nodes became more con sistently enlarged, and in the instances in which this occurred the cause was almost always infiltration of the medullary zones by macrophages, which no doubt migrated theact from the pulmonary tissues. The cor tical follicles did not enlarge and often showed signs of atrophy. In both the rats and liamsters the reaction in the pulmonary fjtnph nodes was even Jess marked Undoubtedly the most prominent lesion discovered in this series of animals was pres ent as chronic bronchiolitis and bronchial ulceration, with emphasis on the former. The disease was progressive in nature and de structive in its effects, although the tendency to epithelial desquamation, so characteristic of the reaction to quart* dust, was not present. The bronchiolar lesions commenced early in the guinea pigs and hamsters but were delayed in the rats. In neither of the latter groups were the severe grades of obliterative bronchiolitis or bronchiolitis deformans, which characterized the guinea pig response, observed. In the rat the stTess was rather on bronefejoiar ulceration and peribronchi olitis. As the dusting proceeded beyond the first year of experiment, the inflammatory re action in the bronchioles gave way to pro gressive distention and distortion. This change was brought into sharp focus by the increasing cellular deposits around the air passages. Toward the end of the second year the crenated outlines of the hronchiolar lumina were thrown Into sharp relief by a SFfiBCT OF fNHALEO HYDROUS CALCWH StUCATS roaoked teodeacy to peribronchiolar atclec- inhalation, and soon after tftfc strands of U, v/jth cpitheHaluatioa of the walls of the shrinHog alveoli and cellular iofiitrarion amoeg* these mmute cystic spaces. This change produced a microscopic sectional collagen may be perceived among the ceils. FSbrosfr proceeds sk>w)yi however, before * the end of the 30th mootivaf dust exposure. Thereafter it is detectable m increasing effect resembling multiple adenomatosis, but amounts, particularly in relation to the ade as there h no lack of differentiation of the nomatoid areas around the bronchioles. cellular components, no neoplastic change Fibrosis also appears prominently in local could be postulated. This adenomatoid pat areas of consolidation, which, become pro tern was sees only in the guinea, pigs, but gressively commoner toward the end of the as its evolution was in the nature of a de layed phenomenon, it Is possible that it would also have appeared in the rats 906 hamsters third year of exposure, la arumafs kilted, respectively, at 33 and 36 months from-thc start of the dusting, extensive areas of lobu bad exposure been continued in their cases lar consolidation could be found, and similar beyond the IStb month. consolidation associated with cystic disten Phagocytosis of the. inhaled dust could be demonstrated in all animals from the com mencement of the experiment. It was most rnai/fad *0 the case of the guinea pigs and least prominent as a feature in the case of tion of trapped bronchi could be seat in sev eral of the rats killed at the ? 5- and Ifc-rponth periods. No acute tnfiaimratoty process was demonstrable to account tor these results. Asbestos bodies of an elongated, slender, the hamsters. The phagocytes were domi-. tapering, misofe variety were demonstable oantly sGononuckar macrophages until about by oiJ-imroersiou microscopy from about die fiiv! end of the first year of the exposure 15tb month onward hx rats and hamsters and r.'Jjeii multinucleated giant cells commenced from the 18th month onward in the guirfea \<* be substituted in progressively greater pig. Occasionally opaque dubbed bodies number*. At the same time these giant cells could he found, hut in most instances thi- grew m sire so that they often filled the bodies were difficult to bring into focus aud aivecH efrmpkttfy, and toward tl end of the tended to be curved and spindle-shaped. fW! year of exposure the giant cells replaced Often they were intracellular, being partly '.he mononuclear cells? almost completely, eoguffed by one or more macrophages. None especially around the distorted bronchioles. were found Jj'ing free within alveoli. They M time, passed, their cytoplasm beesme in- were so constantly found in association with ^^singJy more acidophilic and their centers the areas of fibrosis that the conclusioa of a more charged with ingted particles. There causal relationship between these phenomena was no evidence of necrosis of these cells, is almost inescapable. tfuch as occurs in experiments with fitieiy Emphysema of the hypertrophic variety divided quartz dost and silica fume, which appeared as an early sign in the hamsters, provoke similar giant cells. in which it w*$ present to a quite marked Interstitial cellular proliferation and infil and widely distributed degree at the end of tration are a late sign in all three species, the 18 months of dust exposure. In the raj* ft commences first toward the end of the ninth month of exposure, and for the suc ceeding six months it is almost entirely lim the lesions mere also consistently from-an early stage but to a lowci*3era^ than m the hamsters. In the guinea plpTon ited to macrophage accumulations around the contrary, hypertrophic emphysema was smaibr blood vessels and bronchioles, at the contrastingly absent during the first two angles between adjacent alveoli, and m the year* of the experiment. In the final 12 Interlobular septa. Among' these macrophages months, compensatory emphytesna was man may be found isolated eosmophllcs and plas- ifested as a prominent lesion silhouetted macyte*. Fibrocytes first make an appearance against the foci of cellular proliferation and between the 15th and the l&H month of dust peribronchiolar awfcNfrsw. f .147 SCHEPERS ST AL. Unlike in many ether dust experiments, culous disease and the tissue reaction to the (here was no marked tendency toward syb- inhaled dust will develop aimuhaeeously. pleura! congregation of the hydrous calcium In the reactivation-phase experiment, the silicate dust. Consequently the reaction at animals, after being infected with the tubercle this site was minimal and delayed. The most bacilli, are allowed to Jive in a normal at conspicuous changes occurred in the rats mosphere for several months before being where there were occasional subpleural cellu exposed to dust. During this period the lar condensations and a recurrant tendency tuberculous lesions generally regress, and to the formation of interlobular adhesions. in some instances complete healing by reso In some of the guinea pigs which outlasted lution may take place. Following this inter three years of exposure to the dust, fod of val, the exposure of the animals to some subpleural cellular proliferation attended by dusts has no significant effect on the usual giant-cell accumulation were demonstrable. course of the tuberculous process, and the The relatively marked macrophage infil tration of the pulmonary lymph nodes con trasted sharply with the paucity (A giant cetis among them, with the minimal amount of interstitial fibrosis which ensued, and with the absence of asbestos bodies. Periadenitis erf a mild degree became a consistent hading lesions continue to regress, while exposure to other dusts may cause the tuberculous process to become active and to spread. A predisposition-phase experiment is one in which animals are exposed to dust for several months, are then infected with the tubercle badlli, and are immediately returned to the in a majority of animals beyond the end of the first year of dust inhalation. Deposition of fibrous strands around die lymph nodes JoMowed successive phases of afferent lym dust room where their exposure to dust h continued. Is this phase the effect of a pre vious dust exposure on the early course of a tuberculous process can be studied. phangiectasia and macrophage transportation -along these channels, with littoral arrest of increasing numbers of these cells. The lack of fibrosis, except at sites where asbestos bodies occur with greatest preva lence, is indeed remarkable, the more so SmuLTAstous Phase: Reactjos ix Guinea Pi# INFECTED WITH TuSS&CUi BACiUJ at Onset or Dust Jnkaiatiox In the first experiment jn which animals were infected with tubercle bacilli at the time when regard is had to the dense cellular in filtrations which ultimately ensue. One is led to the conclusion, therefore, that the hydrous that their exposure to the dust was started, 25 guinea pigs were used, but an epidemic of pneumonia during the first 10 months re calcium silicate dust alone, except for its chrysotile component, is nonfibrogenic though it provokes a cellular reaction. duced to 16 the number of animals available lor study. Two of these died at fourteen months, apparently from progressive tubercu losis, and two others died from undetermined EXr*OSUJM5 OF TUBERCULOUS AK1MAL5 causes but not from tuberculosis. In the re maining 12 animals the course of the tubercu lous disease was followed by killing l ox 2 animals at J, 6, 9,12,15,18, and 24 months after infection. In 9 of the 25 animals the le sions were multiple, isolated, and healed, often with central calcification. In six of the remaining animals the lesions were still circumscribed but showed neither a tendency to heal nor to spread even at the end of 18 tubercle bacilli of the R5 strain by an inhala months. In six other animals there was a tion method and then are immediately moderate tendency to local spread of the transferred to the dust room. Thus the tuber- tuberculous process, while hi the remaining 3-1$ ,,.*v* v> v v > W, EFFECT OF INHALED HYDROUS CALCIUM SILICATE T&&iz S,--Comet ej Death Gtdneo Pigs Esmond, by ItPtdefie* to Commercial Hydrous Cakiam Silicate Dust end AUc Injected toilk TubeecU BacilU of the & Strosg Trt*t B^celsat ataolhuMM* ptMe......... BetcUeeBue phw........ PMMceitMB phj*.... Oactrai: Group A......... 0r*SP B ......... OasMefZMiUi Ppeoaoatt Perte*r*ti* farROBjeu OUctOhm *oui Aosmtk. Suite*. Ho, No, Ttr ot Death*, No. Oftuit Dut6i.a. Vnr CMC be*the. Per No, -Out Deettei, No, CPheart 1 HA I J0J> 7 u t M U HA t KB 1 tn 6 tti *St4 l 4 . UA s HA 4 U.? e*e u.r 3 13.0 1 to s,, Kb e HA animal, which was killed at 15 months, the lesions were widespread throughout the Jung but fibrosis had been produced. In an at tempt: to develop a strain of guinea pig reAslant to the infection that had caused the pneumonia, some of the animals were used &f breeding during this experiment. The two animals that died from progressive tu`wculosri (at 14 months) and the single snimai (killed at 15 months) that exhibited widespread lesions were all used as breeders during the experiment, as were also four other amcnaU in the experiment, which had failed to show extensive disease. Owing to the dement of uncertainty introduced by this factor of breeding, and also because of the high mortality from pneumonia and to verify the suggestive evidence of stimulating action of die inhaled dust upon tuberculosis, the experiment was repeated. Y\su?A--Count of Tuberculosis Induced m Gttinsa Pigs by Infection with Tubercle BacilK - of the Hi Strain Control Study: Infection Only; No Dust Exposure V GvEjc. Ws. Ud. Os,,.., 8}~ sj- r*` V..... 74; . (S' : 91. AJHf ^fo-Ooa. D*?e X0 S* VA flfi) ns s Ol) tso ttf w txed ED*3 tiM srm EBed SOW EfiM DM DM RIM EBed DM SUM KIM DM KIM EUed SUM Kim KIM SUM Silled SUM SQM KUM EKi1lteMd SUM SUM SUM SUM KIM SUM Kited PolmooeiT leek** SaactSoB Id FuhnoBwy WraphNode* \ ArrwM epmAiag Tot*Kk*. Yuberai. outi. No. Boo 3 te - f 4 % 6 ,,444 44 t 4 n t 0 4 1 ? u l 4 t ,$ X 6 8% t t .. 8 3 * 6 5 4 3 0 ToMrde XKsMsdasaoB OeidS- _ EUerw Bono* -- mBoo ptouitU seat 4 + Boo Liver ,, ~ - U 4 T4 T4 4 T4 T4 -H+4-f -A- T+ ++ 4 + ++ ,, -H- 44 T444 T444 ,, ,,++ + ,,4 tt 4 , 4 .. +-f 4 .. +4- 4 44 4 ,, .. + 4-4. -*4> f + 44' +4- f+ 4_V .. ,. 4 .. l .. 4 .. 4 , 44- 44- 4-*- K 44 4 4-4 4> 44 H* , > oycitoB.: 4, aUfbt w*fUoo; 44, taodereie nsetlou; +++, adeuecd re*JoD: T, tubercle fonnetioo. i 39 SCHBPERS ET Al. Table 7^-lnfiuenee of Jnhaltd Commercial Hydrous Coisium SiHeate Dust on ike Course of - Experimentally Induced Tuberculosis m Guinea Pigs Sknolunean Phase: Animals Received Their Tu*roitaws lafcc&xv nd Started Tferit Period of Di Exposure Simulunecasl; Out's* ft*. So. * l i 6 fe %s IS ? e w. a 9 a % n a . 17 a /K s8 'B V-/ M s s a te&uet, * D*r* 0 w K ,,H1 iso m us it* m ISO UK SM m ste uo ti* ns m tl ssd m 4K a; m SB e m no rx pio pad Wert SQM KHM 6*0 Oka pied Ilum SUM PM PM Plat sum sum PM SOM SZBat Bled Stad SSM row SM DM &*S DM SUM SUM JtOtod ptaicwiKI strait lutarelas, No. t t te i e i ? i t t 6 9 9 6 .. ,. s 1 6 - To+xr aUmis 4 4 4+ 444 44 .. ,, 4 4 4+4 +4+ .. 444 44 44 44 CIUtjo fieurU* << 4 ,, 44 44 444 44 4 ,, 444 ,, 4+4 +4 M .. 44+ 444 444 44 444 ,, 4+ +4 .. XtOjsrt*BXOt +4 + 4 4 4 + +4 4 4+ +4 +4 44 44 44 4 4 +44 +4 , 4 4 +4' 4 44 +4 44 +4 OtoM5t0*U0S -- lUwr OilCHI* < 4 4 < 4 44' 4 + Urtr N+ 44 4 4 4 4 4 4 4+ 4 4< 4 + 4 4 4 >> 144 T+ ,, 9< Spteeo 4< 44 444 M 4> f. M *+++ r++4 flBbota: 4, ilisbt teactioe; 4+ inortfcnM* rutettoe; 4rt-f, **Uoo; P, flMwI*; X, hmtmIb; T, taber. When conducted a second time, 30 guinea pigs, instead of 25, were used in this simul taneous infection experiment. The animals were killed in pairs for study at 2, 4, 6X 8, \2y IS, and 24 months after infection. Again the incidence of pneumonia was unusually high, six of the animals dying from that cause dur ing the first 8 months of exposure and two more during the following 16 months. An additional three died of pericarditis, one of peritonitis, and two more of other causes (Table 5). This left a balance of 16 animals which were killed as planned. The results are assembled in Table 7 which should be compared with the control study recorded in Table 6, in connection with which the same culture batch of tubercle -ISO tadlU was used but the animals were not exposed to dust. As may be seen in Table 5, the mortality rate among the control group was but 117^ as against the high rate of 46.6% found in the animals which were caused to inhale dust. As these experiments were conducted simultaneously and in the same laboratory, except that the animals receiving dust ex posure were even better protected from out side contacts, the different death rates may have some significance after all. The numbers of tubercles which developed in the control series did not differ materially from those which were discovered in the animals exposed to dust after infection. In one control animal there was a marked spread which caused the death of the guinea EFFECT OF INHALED HYDROUS CALCIUM S1UCATF. : g. Massive caseatiag lesions were found ; in the lungs, the liver, and the spleen. It \ was suspected that this animal may have been ) iacddenially infected with virulent human ;tuberde bacilli, Consequently, bacilli were . recovered, cultured, and subinoculated into : the groins of four iiealthy guinea pigs. These animals developed local abortive ksions char; acteristic of the Ri bacillus, and no systemic : tuberculosis ensued. By this study it was fairly satisfactorily demonstrated that Guinea Pig 73 was unduly susceptible to tuberculo sis. In the guinea pigs which were caused to breathe the hydrous cakium silicate dust after infection, localised spreads of the tu berculosis occurred in 13 out of the 30 cases. In font of these the tuberculous process was quite advanced, and in four others it was moderately marked at the time of autopsy. It should be noted too that five of these spreads occurred during the second year of the experiment, K e., kmg after the tubercles stouid have been arrested and healed. At tention should also be drawn to the presence of cavitation within two tuberculous pneu monic areas in Guinea Pig 25. Pleural adhesions of a chronic tough va riety were also quite common in the animals receiving the dust exposure. The pulmonary lymph codes showed a greater prevalence of late active tuberculous foci, such lesions in the control animals having usually disap peared from the nodes before the end of the first year. From this simultaneous phase experiment it would seem, therefore, that the hydrous calcium slieste had a mild to moderately ad verse effect on the course of the Rj tubercle infection. Reactivation Phase: Couase or Tuasaeutosis ix Guinea Pics Which We*e Exposed to Hydeous Curium Simcatx Dust SEKWAL &OKTBS AVTE* IXFECTJON wrrs Kt Tusehcle Bacilli Infected guinea pigs were placed in the dust chambers at intervals of two months, j, e., SO at two months, 8 at four months, and 8 more at six months after infection. In order to follow the course of the tissue reac tion, a pair of adimals of the first subgroup (two months in normal air) was killed after only 2 months of dust exposure, and, in ad dition, animals from all groups were killed in pairs after 4, $, and 12 months of exposure to the dust. Examination of the tissue of the dusted animals failed to reveal a significant reactivation of the tuberculous disease by the inhaled dust (Table 8). Only five animals showed evidence of spreading pulmonary tu berculosis,. In three the disease was tainiraal in extent, and in two others there was moderately extensive local spread. Casea tion persisted m one animal to the end of a year, and slight to moderate iod of fibrosis could be discerned in a few animals, suggest ing that not all the tubercles healed by resolu tion. Chrome p&uritss and pleura) adhesions were present in 10 of the guinea pigs, which was considerably in excess of what is cus tomarily found in a typical reaction to the introduction of Ri tubercle bacilli. Pssseramation of the tuberculous process to abdominal' organs and to the pulmonary lymph nodes did not occur m any bit exceptional cases. Guinea Pig 52 was probably one of these "sports." The term "sport" is given to a guinea pig in which the inhalation infection with the attenuated bacilli is not confined principally to the lungs and pulmonary lymph codes but extends also to other organs and produces in them tuberculous changes of sufficient extent to be recognized maeroscopically. Since "sports" represent a de parture from the normal pattern of tissue reaction to attenuated tubercle bacilli, whether the infection is combined with dust exposure or not, such animals must be ex cluded in assaying the effect of an inhaled dust upon a tuberculous infection. It is be lieved that ^sports" are animals whose na tive resistance to the attenuated Ri organ ism is unusually low, Support for this beiiel is given by*experience with quartz dust, a definitely hazardous material which reacti vates an initiation infection produced by attenuated Rj bacilli but ordinarily is not as sociated with tuberculous extension to organs other than the hmgs and pulmonary lymph nodes, 3SI r s SCHEPBRS RT At. Ta*U3 &---~tufiu*nee of Inflated Coirmerciai Hydro** Cclcivm Silkate Dust on lb* Court* of Erfentnenicliy Induced Tuberculosis in Guinea Pigs Reactivating Phase: Afltmiti, After Reosrktg Tb<jr Tobercutous Infection Were Allowed to lire in s Normal Environment for a Period of Two to Six ifoaths Before They Were Exposed to Dost FtdBa&tn1 XeelOM HweafertaB Spread* Msm to Dost, PI*. No. Dor* FtC Tubercle*, Taber* Ow*, * Hoi**!* Kfl. cttiocV Boo FtbroU PMrid* ateot ExpMUft to Du*t Vu 6t**tto Two XofiUu Alter JatoeiMft IT 0 DM u 1J DM s4 4 4 u 4Q fifed t a to rrtuA s n to a a Ito S/tlUA a fe KUM tei MO EfiM a t B MO *<** J3 m HUM s a 4^ M toe 19 44 4 40 m gtru* 9 4-4 44 EkpmeiK to nut Wu Sure Poor Vesta* Alter btfeetioa 4 4 M 4 44*4 4 + 4 4+ 4-f 4 4 44 4 44 44 44 46 ISO t s liC SOM 8 44 4i MO Fl&# t a* MO K0U4 % a set BOM 44 *6 Hfitad t4 *pcstt to nut wtt Bucua Six Meath* Alter tofectfes 44 4% 444 44 44 4+ 44 44 44 ,4$ U7 DM to IS) SCM Bt ISO SUM : es MS KQM MO Eflfed 6 44 %4 -f 4*4 44 7 4 .. 4 ,, 44 l 444 44 44 ass i* ass BM 6 ,, 4 + *+ 44 44' k* Tuber. ukii 4 4 * 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Urte T4 ,, .. ,, ,, . BraboU; 4, *a*bt; 4*4, *rU; 444., aAraMd; T. ta&cK&teiU, Wrtaa 44 4 ,, .. . T444,, PBEoiarosmos Pbatv. SxAcnctf i Gtroax Pics Ikfktso wits Tupsact* Bacnxi Terse Mouths After Tanias Exposure to Dost Was Started Au experiment of this type is a severe test, because & dust that is onty very slightly toxk may produce tissue changes which, though minor in character, may be sufficient to alter profoundly the development of a fresh tuberculous infection. In this experi ment, which was designed to study the ef fect of the dust accumulated in the lung upon a newly developing tuberculous disease, 30 guinea pigs were exposed to the dust for three months and then were infected with at tenuated tubercle bacilli. The dust exposure was immediately resumed and carried on for another 21 months. The over-all death rate in this series of animal* was relatively low (Table 5). It may 3S2 be of some significance that the majority of the eight animals that died from pneumonia did so during the latter half of the dusting phase. It is also significant perhaps that local and diffuse spreads of the tuberculous process had occurred most commonly in these animals prior to their terminal fatal illness. The prevalence of such spreads in this series of guinea pigs does indeed appear to be significant (Table 9). Six animals showed marked local or diffuse extension of the dis ease, and in seven more this spread was of moderate severity. In an additional 9 cases there was alight spread of the process, so that a total of 22 animals reacted unfavorably. Cavitation occurred in 2 instances, and pleural extension in 10 of five 30 guinea pigs, One animal died from a pneumonic tubercu lous process, EFFECT OF INHALED HYDROUS CALCIUM SILICATE Table 9s--Influence of Inhaled Commercial Hydrous Ctdeiuuf SiiicSte P*at on Ike Count of Experimentally Induced Tuberculosis in Guinea Pigs f Predisposition Phase: Animats, After Being Exposed to the Dust for Three fcfaaUu, Were Infected with Toberde Bacilli f the R. Strsia sad Ham Were Immediately Returned to the Dust Room Where Haear Dust Exposere Was Contused Until Death rrmbef Snacon to Lost Atur Gita* fateuoe, Ptf.X. *>* vn 8 8 ft 98 ft B ft 81 ft as a 3B ft 1ft a Uft 87 UP iU Oft w ao 1U no m *46 SB as MS K0 216 846 88 m 1B MS m 60S u; fe m ft K. 4ft 1U m ue 4ft in 830 m ft m ftp nie TTTW' SUM KBM ttkd TTM DM KQM ESQftd Tm-x Silled EUed DM Died SUM EBM trnw smw* DM ftlTUl lS,TO< DM DM DM DM row SUM p>rw< BBed nwi / ...... . PulnaBary Lftta* irwM Spnsdtu Toberelaa, Ttfxt- Curh* Ho. aOnlt ties 4 4 ,, 4 4 4 ,, %4 4? 17 4 tt 4 U4 u 41 44 u4 ,, < 444 444 t +4- e a4 .. * 44 8. 44 444 ,, t 4-4 ,, -h4 4+ +4-4 ,, .. 4-4- 4-44- ,, 4+4 .. .. 4 4-4 4 ,, 6 4- j 4- .. PMriw ,, ,, XXoanlaatioe FlitarvQUT LBBDbHodft -- E&Jerr* neat MlOlH U-jflr .. ,, .. ,, .. +4 4+4 +4 4-4 4-4 ,, 4 4 .. 4 44 .. 44 44 44 44 -44 44 44 4 4 4 44 44 44 4 444 444 4 44 4 44 4 4 4 44 4 4 4 4 4 4 4 ,, .. 4 4 4 4 .. 4 4 4 4 .. 4 4 4 4 4 .. Betas *4 t SrtaBo**: +, d*Bt er adplet iwtloa; 44, ftedsnU mettos; 444. mtstuS rttedoo; T, tutwcaftfii. It is of interest to note that the extension of the disease was almost entirely confined to the pulmonary tissues, tuberculous Sod being detected in the spleen of one animal only. The reaction m the pulmonary lymph nodes was not of a significant nature or de gree. These findings indicate that a tuberculous infection which originates in guinea pigs several months after a prolonged exposure of the animals to dust of the hydrous calcium silicate product was initiated may be unfa vorably influenced by the inhaled dust. A separate control experiment was set up, us ing 25 guinea pigs, as the predisposttionphsse experiment was started at a later stage than tbe preceding studies so that a fresh Ej culture had to be employed. The results ob tained were so similar to those given in Table 6 that the latter may suffice for the purpose of this paper. ANALYSIS OY TISSUE OK EXPOSED ANIMALS Chemical analysis of lung tissue of unin fected guinea pigs that had inhaled the Hy drous calouzn silicate dust for periods up to 36 months yielded the data reported in Table 10. It will be noted that as the period of ex posure became longer the values for the tis sue ash gradually increased, thus showing that mineral matter was accumulating in the lungs. There was a pronounced increase in the silica component up to about 30 months and then slight decrease. This phenomenon is illusory! it is due to the relatively rapid rate at whJeh inorganic matter was deposited \ 353 w SCHBPEXS ET AL, in the lung at this stage whefe the tissue reac tion suddenly blossomed forth into the fullblown disease process. Comp*ts.We resuits have been obtained in The Saranac labora tory ifi inhalation experiments with other dusts. The total amohnt of silica which accumu lated in the lung was about a third of that which nay be<femon$trated in the pulmonary tissue of guinea pigs exposed to quartz dust for a comparable period, COH&tBNT The first point which may be considered is that the commercial hydrous calcium sifi- As the chrysotile dust is capable of pro voking fibrosis in guinea pigs, it may also in the case of the present study have been the cause of the focal fibregenic response, so that the hydrous calcium silicate component may have to be exonerated. It seems likely that the giant-cell reaction was largely an effect provoked by the latter component. At tention should be directed to the lack of ob vious necrosis in these cells, In this respect the dust differs quite markedly from quarts dust and silica fume. Indeed, necrosis was seldom a feature in this experimentally in duced disease even to the presence of tuber culosis. It is possible, therefore, that ah Table ]0.--Analyst! of the Lungs of Guinea Pigs Esfasti to Coiamrrc'usl Hydrous Calcium Siikats Dust period of Kxwun, Me. 1 4 8 X IS IS is u r? SD S3 m act,p<? One of E>eriecU4 Loa iS as w 4M U7 1,02 (2S 0,19 iSt 44$ 447 tM 447 kU&enl OomaaMs Peuw* Laos SlOi, Per Cast 0X8 040 0.8S #.a 0.48 94S M* CM 045 0.M l.U 0.1$ 048 OkO, ItoOeat O(* 0.08 040 at OAi 0.16 0so 911 CIS 0,10 oat US 0.14 3U0, tot Ceat m 04$ OSH M o.u 0.14 m CM tsn 01? 9M 010 0.70 XXiem opnrKflwBUi l icuu Aib 810., t* Oeat 4S3 <44 6.40 M3 017 w.a VJM U4S 3841 1S.74 30.03 It* ao CaO, FtrCent IM 1M tst tM lJ tM 146 110 tn 140 *42 XM tat **o. Per Out too \SA L *10 tea 412 40S L74 1*3 8.12 ojz 843 *04 -ate product, studied in the experiments just described, really provoked two underlying pathological processes aseribable, respec tively, to the calcium silicate and to the chrysolite components. The terminal syn drome of peribronchiolar atelectasis, fibrosis, and; adenomatoid change was, in fact, of the same kind as that which has been repeatedly produced In The Saranac laboratory by means of inhaled asbestos dust. The lesion of experimental asbestosis has somewhat more fibrosis to it and shows less of a cellular reaction aad the giant Us seesv in the pres ent case are less commonly observed. In character with the asbestos lesion is the ab sence, to the present experiments, of fibrosis of the pulmonary lymph nodes in which no asbestos bodies could be found either. 3S4 though the hydrous calcium silicate dust stimulated the proliferation or local accumu lation of cells it did not kill these cells. This point is well illustrated in the case of the bronchial epithelium, which proliferated as part of the process of chronic bronchiolar in flammation but did not readily necrose or be come desquamated as in animals exposed to quart* dust. In many of the worst seeming adenomatoid or cystic lesions, the bronchial epithelium even retained its ciliated epithelial surface. The evolution of the adenomatoid reaction is clearly revealed to comprise cryptic dis tention of the bronchioles, secondary papil lomatous ingrowths into these distended lumina, and peripheral epitheJialiaatioo of* atelectatic alveoli. EFFECT OF WHALED ,.HyDROUS CALCIUM SILICATE , Wty the alveolar ducts and bronchioles must be presumed; that the hydrous calcium sfwuK'have dilated at aa-daffy phase in thj silicate duet transported irozs the Jungs rats was no* clearly revealed. Ho pnndnsal to the lymph nodes, to judge ty macrophage obstruction could be displayed which could* accumulation at the latter ^tes, and it is account for the distention on mechanical probable tliat the dust was more densely con principles. Possibly the cause may. be re centrated in the lymph nodes,than in the pul lated to the tendency to peribronchiolar monary tissues. This suggests that the atelectasis. Perhaps a ncurogeuk mechanism stimulation to perpetuation and spread of was at the root of it all. To be true, the the tuberculous process may*have derived larger cystic distentions were usually found from the chrysotile fibers rather titan from within areas of chronic diffuse consolida the hydrous calcium silicate. Suqx a con tion. and it is possible that in such instances clusion naturally requires further coufinqa- the distention of the trapped air passages tion through experimental investigation. resulted mechanically from cicatricial con traction. SL'MMAJY The origin of two types of emphysema Inhalation studies have been conducted which were discovered may have similar ex using a coustoerciaf product composed of planations. .While that which developed in hydrous calcium silicate and chrysotile on thrgukwa pigs was definitely compensatory normal guinea pigs, rats, and hamsters and to'-the. foci of atelectasis and 'fibrosis vftach on guinea pigs infected with tubercle bacilli 'itwrTFMinded.and the tmphj'sctna found in of the strain. thB-wts.an^ hamsters^was of the hyper The dust caused marked chronic bronchio trophic variety, both may have had'a com litis, with terminal peribronchiolar focal mon origin in the damage to the bronchioles, fibrosis, bronchiectasis, and epifchelkdiaation The mild to moderate tuberculogemc ef of atelectatic alveoli. The final lesions closely fect of.the hydrous calcium silicate dust mani resembled those found in experimental as- fested itself in local or even diffuse spreads, bestotis and included asbestos bodies. delayed healing, and dissemination, to other The course of experimentally induced tu organs. It is not yet possible at this stage to berculosis was mildly to moderately ad attribute this phenomenon definitely to either versely affected by the prolonged intention the chrysotDe. or hydrous calcium silicate of the dust. components.. The- fact that the tuberculous It seems finely ttet the chrysotile compo process did not persist in the pulmonary nent of the commercial product, rather than lymph nodes, whereas was activated in the the hydrous calcium silicate, was the cause lungs, parallels the observation that only in of the deleterious effects on the tissues of the the lungs were asbestos bodies found It experimental animals. i ,> V/ . j^daiiondtip of* f^artide (bounty ^lAfeightj Slape, and Site ofShr~d3ome 2^ujti M. L- *0fTS, MX, E-M, S**>we UU, H. Y. ................... 3n experimental studies A The Saranac Laboratory, animals are exposed to air-horse do# in rooms B by 8 by 8 ft. in dimension. A dusty atmosphere is treated in the rooms with mechanical dasf disseminator* to simu late the environment that might exist in a mine or an industrial p&uf where the ma terial under study is being handled, with the exception that concentrations in the dvst rooms are usually maintained at a higher level. During the experiments numerous de* terminations of the concentration and partide-site distribution of the air-borne dust v are made, and certain studies of the parent material also arc carried on. From the de terminations made on quartz dust and on several varieties of submicron amorphous silica dust, data have been compiled to show relationships between the count, weight, and sin oi the dust panicles and to compare re sults obtained with certain sampling methods. fiUAJRTZ DVST The quartz dust used in the experiments was a commercial product with a silica con tent greater than 99%. The material was finely pulverized, and 9855?-99.5% of the air borne particles seen at a magnification of 1000 rinses were smaller than 10/* and 88%95% were smaller than 5#t in size. Pabticlb Shape When observed at a magsuficad'on of 1<XX> times, quartz particles that had been settled Recorded for publication July IS, 19S5, ftxfasTrta? Hygiene Engineer, The Saranac Laboratory. 335 on slides placed in the dust room have the appearance seen in Figure 1A Here the small particles, 1* to 2^ in size, seem to have a fairly regular outline. An electronmicrograph (Fig. IB) of quartz particles from the same dust room reveals, however, that the small particles are really quite irregular in shape. SlZB-FfiHQUfcNCY DlSTVBUTlOK Measurements of the particle size of air borne quartz dust were made on samples col lected by means of the electrostatic precipi tator and examined at 1000X magnification, and from those measurements rise-frequency graphs were constructed. Representative graphs, shown fa Figure 2, indicate that the median particle size ranged from about l.Sfi to 2.0ft- A graph represenring the partide-ri20 distribution of the parent material is also shown (Fig. 2). pARTtlXa COOKT TO WUMST RaWO Numerous samples of the atmospheric quartz dust in the dust room were collected simultaneously by means of the midget impinger and the electrostatic precipitator. The dust concentration on a count basis was determined from the impinger samples and on a weight basis from the precipitator samples, From these findings the number of panicles per milligram of 4ust as calculated. A sum mary of the results is given in Table 1. The values reported fur the number of particles per milligram of the atmospheric quartz dust depend upon the optical system employed for counting the particles. When the standard light-field technique was used, the average count for the samples was about 100,000,000 partkles per milligram, although values as high-as 164,000,000 and as low as 61,000,000 were obtained. Eighty per cent of all of the Rm 4 OU AR T 2 OUST size pReotiewcY i4 ueon ! *s 10 $c T t> &* 4 3 2 J OA 04 03 02 3S7 * ROBERTS TtJats. 1,--umberKoJ Pohiclet per MilliQtom and Average Particle Stir of v.' Air-Bome Qtajrjj f>#*t 1$ & .' r. * - Sect U*ew 4 tu 2*0 4*0 4 . H61 4 wa 4 lfc* 4 IBM - 7ot*i tBooe O , SiArttl < ; VkVoaol S - rtki* , SeaPk*. l ftluAaMB l Mfrtesaa i. u Average X MssUsuts 5 ftUaltnesi 1 Travt 20 Avtrtce 1 s rtvt** 2 ft ftreftS* 1 Ita&Sttft 2 l Mfatwo* t tritkti 16 Attnp t 1 1 MiJUrao; r Ar*6t . 45 A*4**t . 9ttUUltaC 8 ISM KUteaB> Average y; , _3i*aiiQWa>V." ttlobsuts 4w* JBAstomw Jiiuiicms Trpietl Amtfi 4fee149 4rcne ftUrtnmm ftUflmu.ua fnt*I (Bo*ai! roMCft>asci.e.& StWntts X&b&uis Asr* Avarvc* Average Lightywd Oouat, Vta M tt m 03 us as 104 U tu> a u 09 m 104 *' VS IS * (0 m 10 t 1& m eg m m 0 0 OS vu Uft 0 n 210 - 0 0 0 IV Sftfk' 9kJA OOQftt, MOUM* too , ... 1 ... e >t 4M ... m Avnw Onaoo&S Partiek Bis r UtbV yieM oousa &*WSHU Oauot.ji SlS>ipb,s 14 11 uU 10 1.7 t 1,4 14 l* ao U t> U IP 24 14 14 u ... IS .l U as 14 J4 34 1A J.4 *4 U 14 u M 14 X4 I< IS 14 u vs 10 1* 1ft 9 >< ... ... ... aai ... ... ... si* ... an . >. ... tM ... a* xsa ts < . ..... is ift J,ft IS ... 14 ... 1.9 . L0 14 ... .. L4 li iP ... ... U ... ... tJ ... 24 . ... tx ... * 14 24 14 ... 14. .'.i U 14 ... !A ... 1.4 1ft w XI ... to S' * values determined were within plus or sswittS .corresponding to the limit of visibility in the 'J -. twenty per cent of the average value.iFor an lght-fi?ld microscope. 1c the studies at The j.' *, j1 optical system yielding a semidark fieJd^. the Saranac Laboratory the age of the dust cloud average count was increased to abwt i|7Q* was brief,' and the samples were collected 000,000 panicles iper milligram, and'; tit a . within a few ft of the dust source. Thus jT` '.y^rseries of tests with,a condenser that produced the per cent of particles less than the Jitnif of / . ebrtef field, coqnts as high as four ismei visibility of the light-field microscope was at -fT;--^ '>the light-field tours were obtained. -jKvea a minimum. This condition is comparable to f^r "higher ratios of dark*fieid to Sight-field count, that found in a crushing plant or other in {*>.'* up to 54:3 for industrial dusts, have-been dustrial concern where dust is being eon- reported by Hatrf^1 who showed that d&e tmually created within an enclosed area. ratio oi dark-field to, light- field count depends For a number of years impioger samples to </*'_ *. upon the percentage d/s?ribc(KJa of the par control dust concentrations in the experi vis f riefes in a sample above and below the. sire mental dust rooms of The Saranac Labora- 558 PARTICLE COURT, WEIGHT, SHAPE, ARQ SIZ8 tory were counted by both a fight-field and & dark-field technique. A review of samples col lected 3d the rooms in which quartz dust was dispersed disclosed that the fatso of dark-field count to light-field count had % average value of 27; 1, with a maximum variation of about 20% above or below that value. Since the practice f making routine dark-field cousts has recently been, discontinued, only lightfieW counts arc available for many samples. In compiling data for Table 3, therefore, the dark-held count for all samples was taken equal to 2.7 times the corresponding lightfield count, Avxsj.0a pMtncLt Sirs The average size of the quartz particles, assuming them to be spherical in shape, can be calculated from the numtefof paradesper milligram and the specific gravity. Valuta for the average size computed from tbebght-fieM count and from the dark-field count are listed in Table 1. Is addition, the average size taken from size-frequency graphs (Fig, 2} is shown in the Table. The dinien&soo obtained from the graph represents the size of the `'average" particle cm a count basis, 50% of the number erf particles being larger and 50% being smaller than the "average" particle. The sue calculated from both the Ugb4-field count and the dark-field count, however, is that of the particle having the average weight of all the particles. Nevertheless, in spite oi those en tirely different methods of estimating the average particle siic, the vatocs obtained lor this particular quarts dust are of the same order of magnitude EftzCT ov Ariotu Susuvcaos o* LaxgK 5\**ticizs o PAsmcta Count ajsu Avaa^ca pAtncte Six* If a series of 20 spherical particles arc arranged in a size-frequency distribution similar to the distribution determined for the quart* dust In these studies, the series would be I>, l*. ip, 1*> 1.5/*, 3.5a 1.5*, 1.5*, 2/*, 2*. ' 2*, 2*, 2.5*, 2.$*, 3*, 3*, 4m, S*, and 8*. 1 By calculation * the average sire oi tlte spheri<sl psrttck In the series by count/weight dtterrznzs&on is 3.73/*, the average (median) size by the'count method is 2,0#., and the ratio of the first value to the second value is J.86. If 380 particles of s size less thas the limit of visibility of the light-field microscope are added to the 20 particles, the fight-field count wifi sot be changed, but tbe dark-field count will be raised from 20 to 400, and the ratio of the dark-field count to fight-field count wifi be raised froso 1:1 to 2&:3. If for the purpose of calculation a size of 0.5/* is assigned these 380 particles and their weight added to the original series of20 particles, tbe average-size particle on a weight basis in creased only from 373* to $.8G* the average* size particle by count remains 2.0a, and the ratio between the two values is 1.9. If 10* size particles are added progressively to the original series of ft} particles, the ratio of the average particle site by covmt/wtight to the size of the average (median) particle by count increases to a maximum of about 2& and then decreases as the average particle, size by count approaches the larger svse, This ratio would be gteatiy weteased by adding to the total weight erf the series without sig nificantly increasing the number of counted particles. This can be accomplished by the addition of a giant-size particle (30*-50*) to the original esses or by tbe addition oi a tremendous number of submicron particles. In practice a giant-size particle would aot be air-borne very far from its source. CSON SIUCA DUST The new amorphous silica products com posed of particles submicton m size have be come important commercial materials. Owing to the extremely small size of the particles and the low density of the bulk material, the col lection and measurement of thts submitroo dust present real problems to the industrial hygiene engineer, and farther study of such fioriyjdivided material Is needed. i Variation in Particu? Size The typical appearance erf subnucron silica dust that had settled on a glass slide in a dust room is shown in Figure 3-4. The particles k 359 i t I * i Fig. 3.--Silica dust A, settled sz&nuercs amorphous dust; w division equals 12* B, fob" 'kxc* dust; X 50.00&. * . appear to range to si from about ly-to more Uctea? that tiw w*k seen (Fig. 38) are not than 10*, and seemingly the dust particles could be collected and counted in the accepted manner by the light-field technique. When the same material is examined with the electron microscope at SO,OCX) times magnification, it single particles but rather are aggregates composed of many extremely small particles. Much of the air-borne material is segregated ic these dumps. In contrast electronmicro* graplts ol other submicron silica. dust may exhibit an abundance of small aggregates (Fig, 4). Since the particles ate only a frac tion of a micron in size and even the ag gregates, in many cases, may be below the resolving power of the microscope employed in the standard light-field technique, the re liability of the usual dust-counting methods when applied to the submicron dust Is im mediately questioned. Comparison or Aggregates a>o Paktuxs* Data concerning the aggregates and indi vidual particles of several varieties of sub micron amorphous silica dust are given in Table 2. The values on the left refer to the aggregates, and those on the right to the particles. The first column lists values for the trumber of aggregates per milligram ol air-borne dust, based on the assumption that all the dust is present as aggregates and that all the aggregates are revealed by the Jight- 360 ... ' * ---.5i? V*>**V'** * >' '/*J .. - ,-p r . * .**/,,* -.:.v' [S3r%%iat I* > SwW jrV>*V^. -`ASv\ *.-_; ' KA.( Put*** fiU MXIO*1 axis'* ti ffWXW* ;,VY%;V ^:*^S^w<u^*mafii greater than similar, ratios .- **hi-^ust. It has been shown _ section that the presence of a fev^gkctt^b* aggregate or of a very great iTiiiiU. of Bacooated sabmicroft particles in t^KBpkwtQaffect the ratio in this manner. 1'he ''noted,' however, that for the v' p)e cOobenkroo dust studied very few than 10p were reported in standard counting procedure or in the *>;'to *dttt .. ' that [mi plots. e'ttae of the individual particles of suh- Ptnlonwcflgk sJUca determined by mcasure- tig T' y cteroamicrographs is given in *~* # * ^eisni6er^eggncaletf0BQ}i^ Cokmo 6 erf Table 2. The actual density of ^ tm^J.WtlV^DOpotod.Tbe fergejltboae partides Is assumed to be 22, the same '. J* ; differim^j&wetti^'^afterof a^grcfata3ns that of vitreous silica. Calculation of the per bSI%ito flhtal^ lylcotffltXW8?16 *"ber of individual particles per milligram . . and ^pxnpstatiofilCDfaima S), tbeJtrgei* of dust yielded the tremendously high values different* beftna lbe^be oi fee average . In khe last column of Table 2. partkkobtalnoJfcytbecocB* Thus it becomes dear that when dealing * the am/m&A flattedland ttevariaiioo. with submicron dika dust the material can- sathevafoeffor (hemeteofaggregates per net be accurately identified and counted by ttifligraffl obtalped bycount may arise from >the standard fight-fieid technique. A study of yw* ^ *** ekcfronmscrographs of dust samples would aosnptfco that (he dmdty of the aggregates *y>eW information about the size and relative TO the*** that*** Wf^cd bulk numbers of individual particles and aggre- mtterialtod the anstBnption Uni substantially g, Nt application of the technique is all the dust ww hi the form of aggregates somewhat restricted, visible by fight-field cxamhuUon. The ratio a of the sue of average aggregate obuiaed by J summasy the count method and the sise of average { Values are given for the relationship benggregatc obtained.^ the mnf/wtffht *wn the particle count and weight of quartz | 361 4 ** ' 1 i '....... dust obtained in experimental studies with the dust. Dimensions representing the aver age particle size of the quartz dust on a count basis and on a weight basis, although dif ferent, are of the same order of magnitude. Values were determined for the relation ship between the particle count and weight of submicron amorphous silica dust by methods similar to those used for the quartz study. Values representing the average size of par ticle and of aggregate on a count basis and on a weight basis were determined for the dust, <;> V.^UAi, XOBBRTS'T S'. Large differences in these values indicate the nnsaitability of the midget impinge? aed light- T field counting technique lor the counting and ? measuring of the submicron siiia dust. REFERENCES 1. Hatch, T<, and Fool, C* L; Quantitation of Impinfec Dust Samples by Dark-Field MJero*<x>py, J. Stidust Htf* Hj577 (bUj} 19W. 2 Drinker, K *d Hatch,- T. F.: Xwfestrfal Dust: HygimK Significance, Measurement, and Cowed, New Ywk, Inc, 1954. Book Company, 362 f. X 5'Jeau A '' HU9f 14 K&ttMOt* WMmmm t^UT. where he partly recovered and practiced his mmprofesdcm for a few years before his death. ^^^^^Illl^^,lllll**ll^l!1*111^^!1*1^1*/ Ifetot &e war he married Miss Marie I met Dr.Edwardlivfog^Tro^^ who belonged to a well-known Orleans family. f ferst contact with Dr. Edward R. .,;3aldwi and The Saranac Laboratory was to be under Hi medialare far* fetfawmaiy '**fe aprfl, I8PS. At that rime I was an intern disease wbkfalttotn*Jri'faeT4eMd\fa the Montreal General Hospital, and. as Geeeral Ho^jitaL'At'tfals.tiose'be 'artS tt ^ l bad H-n appointed for a sasmd year as the peak oTJUt inooary'dwait * v control, sad be not ocjy. practiced I.visited Saranac Lake before be lay second year in hospital. Dr. wna sway, and when I visited The but sbo .worked,'lapbS* fcbbraiory/fl* ftSanuac Laboratory, Dr. Balden was the 7Twua Saraifa >o1e worker. He was there working on the Dr. Trudeau was bora factor'York oc ^tfixmoses of the tubercle bacillus, thinking Oct. 5.T84&/HU tathe^Dr.'JaiBe* Irtjdeaa, '^tfaat if he could immunize animals with the wva<naaberM:we!HtaowaNewOrfaKtt*rjribtaoees cure might result. Three years family, aad h*j mother's father, Dr.`FrmQfiois tater 2 became a regular worker in the 2oi Boger, was aFr^Affryddan whose' fchoretory- aocoton had be^hyato 1& December, 1892, a slender and pale erarionS. Thv^TfodeiiBV . mofhc,Gf&tt ( young man rang' Dr. Trudeau's doorbell Berger/ w*i*Dr..-yBeigeurtl' ooly Jdaughter. , crk morning and told him that be was a Dr. Trudeau had^ik^brodwr^lid is dUer/J physidan, that he had contracted tuber- hoth oMer-thaC'^hTnwK. TP* father t&d culosU, sod that he wanted to go to the mother separated Aortiynftar Wi birth, tad aanatoriom. He sate that h same was when Dr. Trafetu wo 3 years old, be went l&dward R. Baldwin and that he was from abroad with mother, brother, and grand- New Haven, Conn. A great friendship de- pascatt. Whlktbey westsha4hUiith<j vefeped between Dr. Trudeau and Dr. Bald- -obtaiwd a*dm*ce s4 married French *** and some rime later Dr. Baldwin took officer--Capt ,F< E. .Omart.Bhe sad her w *h* ,*wk of The Saranac Laboratory, husband Bred>itt `Fccttdawbienn tasft her Akm&tiie year 1S96 1 started to work death h 19. <*'+***'.**s a" *? in Theparanac Laboratory. At that time Dr. Trades*! remembered lhtle about h (!#8),pr. Trudeau and Dr. Baldwin were father. During the Gail War hli father was V* ** <* Koch's old as officer in the Southern anpy. He w on the rabbit's eye. The plan of bounded and went bade In New Orleans, , .f?*?1meBt was t0 in>* og tubercle Recorded for pubfoatfan Jour 2, 2SSS. bacjih nfto the rabbit's eye and then, when weH-manced tuberculosis had developed, to i 36$ Saranac Laboratory. " "* Trudcau Sanatonum and &s Dwertor of The ':*. %<: ^<>*".-1^' -WTi^IMPrbsSIONS OF DBS. . Z. TRUDEAU -AND^S.*R.- BALDWiF Start treating fo*. rabbit rwHk Koch's.dd r.Wf foTfr-"** g*h`*'--directions W .The tabercatin. I gave the injectiou&..'TlK tuber- s and did .* -dull the cuim solution was injected subcut&acouxJy - raofoeiby ***** When, boweveri.v'e^rijected into the abdomen, and a dose of au&dent foe vaccine fate guinea pigs, we found that strength giwn to produce a weU-marted *- weB**aficed tebemilosis was. sees ai far heal reaction in the diseased eye.'The re* aatbe-^leea. After this we always sterilised action consisted of an Intense redness of the' oar .'badHary'-esmilsion by beat and then eye. On the eighth or ninth day after:the fooadatedour raceme into guinea pigs so tuberculin injection, all redness had dis* ai to be sure that all germs were killed, appeared from the eye and the area of dis- !o order to find out at what intervals he ease seemed to be less. The same dose of should give the doses of bariBary emulsion, tuberculin, or a dose slightly stroller; was 'Robert Koch used the agglutination test; then given, and there was again suited he found that agglutination was at its height redness of the diseased eye. Hus,dose vu from the 7th to the 14th day following a again given eight or nine days later^and this dose of wane. This is important, and it was repeated until no reaction' appeared confirmed our- work on the tuberculous -eye The dose of tuberculin was iheaiacraMed.,. of..the.rabbit,* when we used Koch's old Constant clearing .of the. disease -occurred,' tubercalio,; taji>ay,.-tiat the local reaction until finally, the eye seemed to be.free erf . bad ceaaed by foe eighth day. disease. . -^ , iltta\weik is Ihe Saranac Laboratory, Toward the end of the First World Wtf.V wetdiowtdKodi's directions but could not a trained nurse was referred to mei suffering; convince \eumlves that the agglutination from tuberculosis of the eye, which ste had was sufficiently accurate or practical to contracted m France. I told her of oar .'< turn stmtinely after a dose of tedllary emul- perience with tuberculosis of the rabbit's * rioa. . eye. and she consented to fate treatment for - About this time we began our work with the disease is her eye. I followed the same", the *tubercukx>psonte test for tuberculosis, procedure as we had used for the rabbit, as used by Sir Afmroth Wright, of London, and the disease in the nurse's eye dirap- ' test was used by Dr. Wright to control peered. I don't think that I would have foe '' <** <* raednes, including the vacant courage to treat another human eye Is foe ** tuberculosis. We found it to be a very same way,-that is to produce violent local reactions. A short time later I treated a can with tuberculosis of the eye with Koch's old tuberculin, but ! used the slow method, that is, ! increased the doses slowly and avoided local reactions, This patient also recovered from his eye tuberculosis. Early in the 20th century--1901--Robert Koch produced his last and best vaccine for tuberculosis and called it 'IsdHary emul difficult and time-consuming test and not reliable. The margin of error was great, and with 100 as a fixed point the test might be 14 below or 14 above 100. Other observers found this also to be true. Wright found that after a dose of a vaccine there is always a negative phase which lasts about three days and that there then sets tn a positive phase. The negative phase represents a period of depression, and no dose should be given while it lasts. He found that the sion." This vaccine was prepared from a culture of tubercle bacilli. The bacilli were dried and ground up into a fine powder in an agate mill. The germs were held in eus* opsonic index went constantly higher after the dose oj the vaccine and that the time to give the xt dose was on the fourth day, that is, at tiw peak of the positive phase, pension in 0.5% phenol and 056% ratine In ThelSaranac Laboratory' the opsonic solution. The powder was not sterilised by test was i *md to be so unreliable that it heat, as Koch assumed that the constant was not u ed as a practical test to govern grinding would kill all germs. the giving of tuberculin injections. It was, 365 ( 4 .*-* KINGMORN ***/.bowW'?3y*i&ticaiiy studied, aad a^p number^rf'terts"were w*fe, and te results *' ?- * were g&e at the Sixth International Con gress on%bercuJosis> which was held in Dr. Trudeau's last published paper ap peared in the British Journal of Tuberculosis owd Disease* of the Chest (1914) and was entitled "Relative Immunity in Tuberculosis Washington, D. C, in September, i^OSAt this important meeting almost all the leading scientists of the worki interested m and ti Use of Tuberculin." The following year he died--1915. He showed by experi ment that the living tubercle bacillus affords tuberculosis were present Dr. Koch was the much better protection than the dead bacillus. honored guest An open meeting was held He regarded this relative protection as not. to discuss the tuberculoopsonic test. Five a "real immunity" but an increased resistance UWstories took part m the discussion, and to superinfection. The relative immunity The Saranac Laboratory was one of the produced by small inoculations of attenuated fire so honored. Dr. Koch was the guest of badJti in guinea pigs is an increased resist honor at the meeting and was seated on the ance but is not a real immunity. What Dr. platform; be was only a few yards from us Trudeau meant by real immunity is an im when we gave our results. The experience to be so near this distinguished man and to be able to mention some of bis results to illustrate same of our conclusions was thrill ing. Our remarks were directed to him and act to the large assembly. We mentioned the negative -and positive phases which Dr. Wright found after a dose of -vaccine, and then we mentioned the work of Dr. Koch with his agglutination test as a control to giving his bacillary emulsion. Dr. William H. Wekh, of -the Johns Hop kins Medical School, was chairman; the following day he stopped us to tel! us that munity such as occurs in smallpox and in other infectious diseases, that is, an immunity which is shown by the fact that, after the disease had been entirely cured, any amount of exposure to the infection will not repro duce it Such as. immunity is not attainable experimentally in tuberculosis. Dr. Trudeau's faith in the possibilities of chemotherapy for tuberculosis was based on what Khrlich had demonstrated for syphilis. He saw do reason why what had been ac complished for syphilis should not be attained in tuberculosis, Dr. Koch had said to him, "Those men from 1 fee! greatly honored to be able to tell you Saranac Lake speak Thataseken (facts)." something about the work of these two out These were only some of the tests which we were doing at this time in The Saranac Laboratory. standing physicians, and I thank you most heartily for the privilege of speaking to this splendid association. 506 *$}emorh& oj?cCeroy %jpAoa ^jardner *A3t S. S1CHARW, ,>,, FACX Soft UU G* The work! of the sky, the stars, the trees, and the plants held him in his first enchant ment The social world, at the world of When the opportunity to prepare a me people of all types, was magnetically drawn morial address on Leroy Upson Gardner to him. The world of communion, which in was presented to me, my mirtd was flooded its osmosis-Eke. state of establishing equilib with thoughts making the approach to this rium interpenetrated the physical and social subject difficult. Whether to admire more realms, established a fioe enduring relation the man or the things he accomplished, X ship to temper his lift. (These axe very few never could decide tor myself. who really knew Roy in this atmosphere.) 1 have read a groat many of the tributes that have been paid to Hoy and l would like to consider him from the closeness with which we were associated. Our relationship began at the Harvard Medical School in 1916. It was carried through with a warmth of friendship that I have known with very lew men during my lifetime. Contentment permeated his very being. No mechanical or fatalistic philosophy could ever be detected in him. He was die essence of the old saying that "knowledge is power and wisdom is liberty." He was dominated by only one code and that was to search out the truth. He was perfectly balanced within his knowledge, his mechanisms* and his purposes in life. His mind was stabilized by a warm religious faith. His scientific pur suits were kept in accord with his youthful training and guidance, and he always had a finely proportioned balance in his general perspective of things about him. Life never And last, there was the world of his own Qeatios*--the environment of his worV and bis daily Activities. I feel most fortunate that I knew Roy in all these phases of hisf life. And k brought to me a warmth and closeness of friendship which is even closer than kinship. Going along with him is his dally activities, getting acquainted with the sincerity of bis heart and the magnificent work which he was doing and the great broad potential of the aspect of its application brought me dose to a mao that I wanted to know and really finally knew. In one of our early meetings at Saranac Lake, one of the speakers in self-defense made the following statement, "When you take stuff from one writer, it is called plagiarism; when you take it from many writers' it is called research.*' K I may approach the ideas of others or possibly unconsciously quote them, I trust that you will keep me in the proper category. became too complex, for he held it calmly within his grasp, unifying all its ramifications into a pattern of perfect significance. None of the modem concepts offered him any entanglements. He lived in the various circles of life with calmness. The trrefe of the uni verse was harmonized into his pattern of living. His clutch never slipped; his trans mission was always shifted with smooth ness--no grating, grinding, or growling. Knowing how to live is the greatest of all arts,* With all of Roy's scientific accom plishments, with his studying of nature and learning the pattern of the universe, he really acquirer an art of living that could be called a way of fife for anyone to follow, That which may have been considered a calamity by som^in his life was really the beginning of his great success, and with it all he de veloped |ja supreme type of judgment, a t 367 i i niCHARDS determination, a source of energy urwquaJcd, he held to the truth which was the guidmg a mirth, and a sense of fine humor and cheer, inspiration of his scientific background. He acquired those qualities that go to make It has been wisely said: up the strong, happy person and became tlx: type of man wc all admire and whom we are glad to be with because of his fine, wholesome, beckoning stimulation---the kind of person who leads us on to greater heights and attainments. He had the qualities that lead and make up leadership--the qualities that have made the world a much finer place Seknee is only one snaU approach to life: it b oat approach to truth, hot in its own domam H i& supreme; it can brook no rivals. It knows do mercy, it is utterly wihuman; it knows no and It knows no enemies. It has no heart, no emo tion, and uo passion except ooe; that is, the pa*, don to think straight Che passion mver to ^ fooled and not to tool anyone else. There h nothing mysterious about it ail. Indeed, its whole passion is to remove mystery, to replace mystery with knowledge. When the scientific attitude of ihtnVSrsg lays hold o! a man's life, it never lets go. From that hour on he ts a changed man. He may be going forward slowly, but he U always going forward, He is always journeying toward greater truths, deeper insights, and a sounder piulosophy-- a philosophy based on things as they are, as eritkal intelligence has been able to discover then, instead of a philosophy drawn from the false world which the wishful thinking of mankind n forever erecting in order to avoid or to escape reality, Roy's scientific background never made him hard or harsh. It was only a cornerstone in helping him to lay one of the most beaatiiul philosophies of life 1 have ever known. He merged his scientific background into his philosophies of Jifc, so that today we can consider him one of the greatest bene factors to humanity in the field of industrial medicine. Fig. 1.--Leroy Upsoo Gardner, W.D., as a young research worker on pulmonary tuberculosis and pneumoconiosis. to live hi. Re had a fine feahnte between mind, emotion, and will. He was systemati cally developed--a man with a keen intellect, a great heart, and a conscience that kept him constantly ai fit* duty. His ability of judgment, clear thinking, and determination seemed to stabilise him with an acuity that brought results in practically all his outlined efforts. His faculty for accurate observation was most outstanding, and his conclusions were always wisely drawn. He proceeded from a strong foundation of facts, because During his period of disability he learned the philosophy of his great predecessor, Ed ward Livingston Trudeau, who taught his patients to cease to rebel and struggle sod learn to be content with pan of a loaf wh cue csxvnot have a whole loaf. This is a hard lesson to learn, but ft is a good philosophy for the tuberculous indi vidual, and to his astonishment he often finds what he considers 0 half loaf, acquiesced m, proves most satisfying. When Dr. Trudeau stated this, he set forth principles which have carried on down through all the great men who have followed him here at Saranac. His teaching is a good one for all people to know, Trudeau told others only what he had learned himself in the school of experience. This philosophy 368 ORfES OF LEROY VPSOH CARLHE* made Roy's mind superior to the state of We all are composites of the people with _his body, and he turned himself into one whom we associate. We all have the sell- of the most notable creative workers of his same nature of the living things in this day asd one who contributed much in cor world to observe. The melodies in all creation recting the environmental hazards of the play to all of us the same tune, and the one mduatriaV worker. He had the ability oi deal great outstanding difference in life is how ing with intricate problems on the level of each one of us responds to this. Roy seemed the cell, molecule, or atom and interpreting to have the outstanding ability of absorbing these into the reaction of the whale organism the best of everything and incorporating it in relationship to the environment. Roy had into his way of living. It was because of She conviction that we can overcome indus these abilities that he always held my ad trial disease just as completely as we have miration. For that reason he has been one overcome diphtheria and typhoid and many of the greatest contributing forces that has other ravaging conditions. He was outstand ever entered into my life. It has helped me ing in removing the hysterical aspects that in establishing tlrose things that I consider have arisen is industrial disease, and he was to be a justifiable way of living. . a great factor in bringing management and While we were close to the same age, I labor to a common viewpoint in making safe admired him from the time ! first saw him . the working conditions of the laborer and in the Pathology Laboratories that lace out ^establishing laws that can be executed with onto Loogwood .Avenue in Boston. At .that "Justice..Certainly, to my way of thinking, he time there were a number of large, two-story t.'^^o-tbtgreatcst factor in bringing us to ~ homes on the opposite side of the street. ._8Sju^2tUBity.pf.thought, and purpose. This Several of us were standing by one of the ..has . fjully demonstrated his humanitarian large windows gating out when Roy ap , tendencies which were, justly activated and proached, and without saying a .word he driven by his scientific investigations. From stood by the window and seemed to be ailhi? observations in nature and his scientific absorbed in something. My eye caught him, . research he developed a philosophy of life which was as consistent and pleasant as nature herself. In all his investigations he established an outstanding consistency. Jlis way of Ufe shows a phn oi itanquiiity, pleasantness which exists in all living things, and, because of these things which he.squired unto himself, his life had such a leavening effect that everyone he enwtmfere<l'*has felt or has been better for haring had his association. This all made fifm as' outstanding leather -- a teacher fimong all classes, noted for his simplicity arid clarity of presentation and most convincmg'iri all his conclusions. Roy was not only one'bf the greatest scientific and re search investigators of his period; he was ope of* the greatest of all humanitarians to ever enter the immortal annals of the medical profession. To actually have known him is \t> understand the truthfulness of that state ment. I looked out, arid across the street there was a large Newfoundland dog looking up and down die avenue, with his paws on top of the gate. When the dog seemed to fee! that the highway was sufficiently clear, he stepped forward, pushed the gate, then backed up a step or two. After repeating this act vari ous times, the gate finally swung open far enough for the dog to walk out on the side walk. I had seen this performance many times, but apparently t was Roy's first time of jseeing the dog go through his act. He stood there with his shoulder against the window frame, clenched his pipe in his teeth, ana with a bare smile on his face, I heard him say; "That is my idea of love'5 labors kt." From tliat moment on I decided that thejre was a man of keen observation and keen sense of humor and that I must get mote thoroughly acquainted with him. That is when our friendship really began. Roy gave us a great deal of assistance in the^State of Utah relating to our occupational 1 .*:;,**& ' ...... rriwayK***' ; *....s.V.fcv '& 'V'r-S >i. \\clj? .4,1 f. < |......... ft .. .vneer-** XtCHARDS disease Uws. He went there on several oesskmg to testify Wore otir Industrial Commlsd<a os problems pertaining to silicosis and its complications. The entire State of Utah and the medical profession feel indebted to Roy for the educational program which he brought to our Industrial Commission, with the type of laws which we established and the simplicity with which these laws have operated and are still operating. All the industries and labor organisations of our state s&\ remember the great service he rendered to us. The Chairman of our Industrial Commlsnon and Utah Labor Relations Board, Otto A. Wiesley, in a letter addressed to me, had the following to say: no conflict wa* apparent In fact, he laid a fbutrf*. don for medical testimony which we have always followed. As ft participant ia the symposium, he txhti&ed the same traits. He was fearless, truthful, factual and gave tbe iiupresstco that he was a master of Ids subject. Socially, be impressed me greatly. With hfc ever-present pipe, his kindly smile, his pleasing voice, and his obvious love for humanity, be appealed to me as a fitting occupant for a `'House Beside the Road"--the kind of man a wayfarer would love to meet on a long journey. Once you met him he became a beacoa light along the highway of life--one of those rare individuals whose living image finds a resting place on the walls of one's memory's picture gallery. And then, when the highway of life becomes steep and tortuous and the storms break, what a blessing It k to take that living image from the walls of memory's picture gallery and find new hope, new courage to ayrvjve tbe storms} Such a man was Roy Upson Gardner. Fig. 2.--Lero/ tiptoe Gardner. MJD., m the role of mdustral hygienist oa tutu of mines in Utah You will read! that I met Roy Gardner os several occasions, and each revealed a different facet of his splendid character. He participated in the medical symposium which you conducted w Salt Lata City in 1943, Again 1 saw him is the witness chair daring the Frank bearings, which was oar first ali-out formal hearing of a silicosis case. My final contact with him was at your son* mer cottage is Cononwood Canyon. Although we discussed medkat problems, tire gathering was primarily social. Brief though my acquaintance was with him. nevertheless I arived at some unalterable coo. efusjone--all highly favorable. Roy was always truthful, a m*n of great moral courage, and as a medical witness he met my standards in every respect. He was a scientist always. He did oot testify for or against anyone. In the Frank case he did a remarkable job He deftly tied the testimony of a medical doctor, highly qualified, into his findings and conclusions so that 370 Oat of our prominent industrialists had the following to say about Roy: Ife was a scientist but, above all, a humanitarian --asking little for himself but giving much. He had a great appreciation of beauty and was deeply impressed by nature's iarishness. He was especially Impressed by the rugged grandeur of the western mountains. His work made him known to the mining industry throughout the world. He spoke easily, slowly, deliberately. He thought logically and opressed himself convincingly. His logic pre vailed. His work will live as long as rues seek the truth. When I started to practice medicine, I became very closely associated with the rnirung industry in Utah. Many of my pa tients were miners of long standing. I soon recognized what poor surgical risks they were. I became interested in silicosis and sent some of the first patients to Saranac in 1923, Again, my contacts with Roy Gardner became dose, and ! followed through all the investigative work performed there. It was these contacts and the association with Homer Sampson and later Donald Cum mings and numerous others that made Saranac Lake such a rendezvous for us seekers of knowledge to come and be fed. With this as a background, Roy made numer ous visits into our locality, and it was upon these visits that we hod ample time to become extremely well acquainted, He learned to >1 , ( '. ' -. **'- --if X&MOXIES OP LEfiOY >VPSONiCARDNBR :- **?='><#' ./ -j >.. '*'*, ve the West Heloved ear **> fMiW Tbe Wgfa desire of the bitfs is my edf-sune pattioa tfctt. fat Java! *fae 5 desire too, ' . . far fitft ay spirit laughs to fling m*t^ber&AUtJKktm f its worfdiy dnffi* down ^X1CJ him were in fais haivdwriting, nd they -- Arndt f free exuffas/Jy, caHj *^y*itartedout:"Tbe Adiroodeda Mfaitt ' . Is fa great companion I the W&satcbest" - *- God meets me in the canyon when Roy bved to visit at the home of jay E buss him in the town, pa*e5 who werevf amocg>,tiieAar^fld /Ar* " * ' --Basss Cla*x jwaeera that cause into the State f Utah. The Wasatch _M__o_u_n__ta__in_s__b_e_c_a_m__e-a very From them he giraned much of the wortOT UnMraM part ofmy'irly life. Myfath hiawy. o( the privWtom tad hudlbipn they took fafc femfly there in 1896, and we home- waa through. On ii hu viiitt to Ut*h there Wautel W all the companions that I haw wro two things that he alway. roqneated- ^ ^ ^ g^aiot, I have never had one to vat our old bometfad and lor me to., wboK wapalkllauip compared with Roy'stake torn into the moamairu. On tmrperou. . 2 was just as anxious as he was to go into trips w eathaaged ma J^kwotttta, and. ^ ^ ^tude ,,d ^.nd a few ^ys. **. .? <w "** towari^thongb^. T^ * really knew how to relax--Use cor tow, ot Me,;the petpoeea, Storing, the. ;laTOattin* teemtS ,0 bring an atmosphere ^ ^ tranquillity about him. After two or three t deyafhe eeeroed to be completely rejuvenated. ^ jou that all our time on these trips runj'daeeart TM ** In teiaxa&m WcdWel tot! F,'4f*| fc " thatIhave metaorieed cmtr tbe yeara-Ttis *** ^ " ld *** V piece ,Is ,eatitJed<rGod .'Sleet* Me to' -the '1 "ti tTM to on many occasions. From thts Mountaiat.'?^ v ' *' God Mta me te'ttg Bnatfim iAeaV'*'^*- ' 'rl <Eia6 aim *S Mflb **.* * r . >v abm tte .oftefftif aiam and <**- c** {.' /V, tee jtftflhf ^mtea ^.',*:** v . i;'V. Up iteere tee teperad agmoi wfll '^y r, ignite m gHaam to tea *y nad cMtrco'wifla vfil aotely & ' ^preach teefr olftey tewiWre 4- la bste ao deoM CbB len iron > 7 Is tour ptim dnoMtent -v-^- ^ Or God* ligte feMfefi ** : . 'terougb tee tapes treat. Scoe av I woe to km Hla ta tee .{eette erf tee *m, *'* f` as tee twtey deer trefl : A A ylfc yreeenr* it tee lertM .* .--etea vtrtyv aqr <a*",a' w* **-' . .No thfaa toitwi Iran akt, - . *M swaciciitty ear ows. t. . J led It leriw mf epW **b< a .--tee pro'/p"h"et-'s ttaiokss p--aa~e~loTn. . As aodeat u tec Easton of tee \ pine tree's ragged cone. * Where pptbeeeas ereaacchh pp tee maeouatr*iiw* u4d > - *teee ftTtmwgtftrtsftfntfs aep tbhe bWtome, AtA ttasc wftb same expecUMy spot, m turning through aa arc of 180 de crees, e could count 35 lakes as we looked -down. Into-(be valleys below. I called that spot my point of communion. The.first time I took Roy to that point we kft our camp at sb elevation ot approximately 9500 ft bout Z30 am. We reached this selected point just at daybreak. It was there I recited for him "The Salutation of tbe Dawn." listen to tbe exhortation of the dawn I j Look to this day 1 For ft is life, tbe very life of life 1 la its brief course lie all the Varieties od realities of your existence; I Tbe bliss of growth, 1 Tbe ftlor$ of action, | Tbe splendor of beauty. Fjr yesterday h but a dream, Aid tomorrow Is only a vision, f* today well lived makes tvtr* ^morrow a vnwn ot hope HT weii'lherefore' * <^y' the Salutation of the Dawn! awe mp --Vim tnt S*asjs .371 4W *;*** i/, ^ - RICHARDS Hoy said, "1 have read that ^aite a few times is my life, but this is the environments! place to bring out its full significance." By that remark I was amply repaid for bringing him to that point of inspiration at that hour of the day. Growing old gracefully is one of life s greatest accomplishments* I have reached the age when the great events in my past, like those with Roy, echo back and amplify and touch with splendor the present every- fashion of the solitude of Thoraui, because 1 have never met a friend or companion of Roy's simplicity. In the creation of my imagination I travel with him io the realities of paths and byways of our mountainous retreats. Many will recall that Don Cummings (Industrial Hygiene Engineer to the Sara nac Laboratory) met his death in an airplane accident a very few miles from my point of practice. Roy had called me early that morning about 6 JO and told me it had been reported to him that the plane was lost. Don had left Salt Lake City to go to Las Vegas. I spent the entire day in the search, and it happened that I was one of the first persons to arrive at the scene of the accident, and I helped to remove Don's body. That eight 1 reported all the details to Roy, and the gratitude that was in his heart is far beyond my expression to relate to you. A few months following Don's death, Roy came and spent five days with me. During that time I had had a very dose friend pass away, and I was asked to conduct his funeral or at least take charge of it, My friend hap pened to be a Mason, and, of course, the part of the program which rested upon my shoulders was arranging for the speaker, singers and type of services I thought would be appropriate. 1 toW Roy that I had this responsibility to perform and asked him what he would like to do--whether he would lake to stay home or whether he would like to go with me? He said, "Paul, I want to go with you." Ffc. 3.--Leroy Upson Gardner. M.D.f as Director of The Saranac Laboratory and as Director of the Trudeau Foundation for the study of tuberculous and other pulmonary diseases. The deceased was a member of one of our largest industrial organizations, and I asked the vice-president of the company to day events of life. That is how Roy's life has affected me. He really never died when he passed the horizon and was taken from our 6ight. He lives with me as much as my lather and mother do on my visits to the old homestead, which still stands after some 80 years of the type of living which really makes a place home. 1 am just as much an admirer of nature in nr mountains today as ever. And much of it is done in the 372 say a few words. I had given the man a few of our very personal associations, and he delivered one of the finest practical sermons 1 have ever heard. During the entire service I could not take my eyes off of Roy as he sat in the back of the auditorium, and I could tell that he was greatly burdened with sorrow. As soon as I had carried out my responsibilities, I went to him and he was still weeping bitterly. "Roy/' I said, "you don't have to tell me what is going through 7 *\>r > ' ."Vi MEA/OK/ET OF LROr. .UPSON .'rf-*1 ... . <;your mind, because 2 know you ut of Dos." He said, -Yes, impressed with this service *'**' tiu* /bowed the true measure VHe was humble, simple, 2nd.I*.ypabkof partaking someone could have orgaoixed ,, _* Jtall As people he met He^ath- like this for Don; I have sat fere tolfeve ^tbe ear** * Uit ** moSt beMtl~ tried to readjust the sorrows of lut >{faave ever seen any man turt by imagining bow that I vns goingte*^ny#%nd be had a beautiful way of pre- his funeral and having someone uyttSfe^rorid and gave the world things about him as the speaker bere'ttd*ytxt* finefeM^de.' has said about your dose friend.** t' */ ' > >^1 bvt* frequently said that Boy repWe west bade home and sat a lea feen^mnstedii his general make-up three great and talked over the problem* of dca&land w fizn&p&rfi. rf bw philosophy exdamged our ideas pettaimng to hTI'taid^^ M^tmeyl be was a Benjamin Franklin; him, "Roy, your heartstrings .fere pulled on very severely today," tad fidd of research, he was a Louis Pnkeur^xodm the field of the general "In my beliefs and faith and fffflfidmwf Z .Cf.principle* of medicine in am sure that you will receive comfort where ^ >* w** a Sir William heretofore you have received ao&hg&tGO# *** fell exemplification of Osier's sorrow a the way Don was tuned.*?him the story of the tittle boy who fed "r"* ' ydw aeel of him ptnu-ed heavy twine. There was do difikufty&gg^ fahb, aaj aspiration. ting the krte into the air. and moa H ^i^ v^fea tafebi * the way *4 lifc .,, ^ . ... * vty i it all his string and walked up tod down ^ h- * jfeo^ih hanilhy and joy. the roadside, maneuvering bis 1at'which' T :Jjk ^ grttjhBje ,,a ^ was entirely lost and enveloped in the efood*. v* 'CoaiudaB tore made hearts happy A stranger came along asd arid, "My boy, . ^He' ^ bimelf eterraiiy what are you doing?" He answered, "Well, And of life Mb** little, sir, I'm flying my kite." Tte stranger locked .;* Be loved the swuetaitss. the pines, and looked and baked and looked* and be ;* f\ Aod ** *t*Ws prattle, said, "My boy, 2 can't see any kite." "No " ^W-Her* we wcwM opes wide the said the boy. "neither eat.'I, bat I'm flying - G"*= * "> ="d I. my kite anyway." The stranger questioned, "How can you tell your kite is up there some where ?*' The boy said, "Well.'J can just tell you by one thistg, &n<3 that U by the puW on the string " With that Roy looked up, d Aad all the while we talked, . God was the eel? one who passed by- la BKBory, my friend and 1 take The paths we made "yesterday," Aftd those BMfttaktous retreats Turn bsek and magnify our joyt he had one of his very choice smiles ef sat isfaction ; he said, "Paul, I understand " Roy, this occasion "The Wasatches To me, Roy's remark^ showing his freat-^ *** tbe Adirondack*!" ness, was determined by the flexibility of his Me*nJtl Medkal Center, 2000 So. Ninth St. E. } ANNUALREPORTOTTHE MclNTTRE RESEARCH FOUNDATION FOR YEAR ENDED DEC 31, 1954 Herewith Is submitted the Annual Keport of the McIntyre Reseattb Foundation for the yea/ coded Dec. 31,1954. The Foundation continued to active opera miners in mines in Ontario and Western Australia, Incidentally, statistics on lung fibrosis and (He number of new cases of disabling silicosis are rarely kept and more tion during the year. The mining and indus rarely published. We suggest that such trial companies licensed for aluminum ther apy continued Its use as an aid to the Voown medical and engineering controls of silicosis. The guppuu of our licensees in four different countries, including 35 states is the United States and 6 provinces of Can ada, enabled the Foundation to pursue the following program s (1) Progressive sponsorship of. the re search project covering the preparation and study of the Gough Large Lung Sections under the direction of the Ontario Depart ment of Health. (2) The of limited services to licensees and the dissemination of general information in response to many personal and written inquiries. (3) Successful research is the Founda tion's laboratories oa the manufacture of an improved McIntyre Aluminum Powder of consistently finer particles, looking toward greater efficiency in treatment values. (4) Providing a forum at the 1954 Con statistical studies provide the only reliable basis for appraising silicosis prevention. (4) Presentation of three papers on x-rayfibn classification of the pneumoconioses. One of these by Dr. Ian McCaUum, of the University of Durham, England, paid par ticular attention to coal mining, Fifty copies of this paper have been forwarded to the United Mine Workers Union at their request (5) Demotwtratiofl of the technique in the preparation of Gough Large Lung Sec tions by Dr, A. J. Blanchard, Pathologist at the Sunnybrook Hospital in Toronto. Dr. Blanchard is working under the direction of Dr. A, R. Riddell, Senior Medical Spe cialistof the Ontario Department of Health, and they demonstrated some of these sections at the 1955 Conference held In conjunction with The Saranac Laboratory at Saranac Lake, N. Y., on Feb. 7, 8, and 9 of this year, ference where many interesting papers on research were presented and subsequently AUJftfitfUM THERAPY released for distribution by the .Foundation. More specifically, last year's Conference at Toronto featured the following; (1) Practical demonstration f aBcosis control, At Mines,--Mass change-room dispersal of McIntyre (Aluminum) Powder was con tinued at mines in the six Canadian metal- mining provinces and territories, in Mexico, in Western Australia, and at the GeevtW Tin (2) Aspects of aluminum therapy in the Mine in England. Two of the Canadian mines under license in Canada, Mexico, and Australia and in foundry and ceramic indus tries under license in the United States. mine*. Gaspe Copper In the east and United Keno, of Yukon, are 4000 miles aptfrt by travel routes. (3) Official statistics on lung fibrosis and 2 Ontario alone, an average of 10.CCO silicosis chest x-ray ratings among working miners have had those daily ptewerk treat- 374 *-***? ANNUAL REPORT .*JOWJMr/OW moitfi for toe pasMO jitdu' rtf Hfem'^oraiqr to ** that m the largest Ca- AastraBa, the Wn^ &eputment l *t& v nadiwa gold-mining center, Timmins o! the Gowiaaart continues as tte'Fendtobft ? Pwwptoe Area, both the death and the ^kes^Byhxw^tsx^a^bx&Mttxnotry' IncSdeftce rates of tuberculous have been tist proride ahudnuA^owder diifcriatl dropping stta^ly since 1945, whi^ is the to* the employees. ------- . .:.-A; . ; V'' year Santana therapy came mto general A* la the prenotn year, we received a ' toing * .. copy of the 1954 report of the chest X-ray >Ai M*sfrei P&x*u.---Thc industry) fibrosis and oI^kIs ratings of the more than' plant licensed usere are practically all In 60CG mining employees of Western An* the United States. There individual treat* trahi, as made at their fmwtd complete meats from small grinding mills supervised swny by the Commonwealth Health Board by ***** continue to be offered to employees The Tristate Hines of the United States continued to , offer > individual toll and therapy-room treatment m aB employees in dust exposure, w. ,/, v: g la operations which may have a silica haz ard. As in mining, periodical chest x-rays are a must m afl such, as wetf as approval of the ventilation and dust-control program In northern Michigan, toenew tt^OCWemv from the appropriate state autljority. O&e per-day White Hne Capper Cbmpasy was licensed to uae'aluminum'in its specially baHt therapf^-room 'ewenaoditiog man than SDloea^r tira&Arwfcfa *S adan <jBailiy at industrial plants Is that the auecess of the campaign against silicosis makes it more difficult to maintain interest in tsdivyduai treatments. and plant* Jicenoed,'White*Ploe';et Abe* Gtncral.--Contacts with industrial plant Foundaffoe retpjirecwtt* as totoedlcal acre- licensees in the United States were main- kes and dust ecetrol, the latter as certified tuned by the Foundation's Medical Director, by the tatt Oaour visit it was pleasure Dr. 7* W. G. Hannon, who also visited the to note Wbata'.-H**** medical services and Porcupine Mining Area in connection with modem hospital"and, faa -resdUtion,-ha 15 the manufacturing methods of producing the ft dssmetorv ooacretf tfrtad rartiiutes shaft, improved aluminum powder. SSOft/deep-T^v c* Dr. W. D. Robson, Medical Consultant, The new uranium'.cries' in 'Blind River Area, Ontario, also have we2dvtoocd pro grams for .yeatiktioo and medical aendees. Since (her ores are itfcwat, they plan to me ahmanma therapy, as now do the Ca nadian Government's two Eldorado Uranium Hines in northwest Canada. . visited mines in British Columbia. Dr. Harmon and Dr. Rohde, Medical Di rector for Mexico, will report separately to the President and Directors on medical aspects. I had in Canada personal committee meeting contacts with the Canadian Mining One Scented gold mine doted from lack of ore; another dtaooataued hr change* room alterations. Two new and larger base* metal mines maintained the number of mm? Institute and with Provincial Company Min ing Associations, and is she United States with the Mining Section of the National Safety Council. licensees. All miners at licensed mines have preonployiMBt and periodical medical chest x-ny examhiations. That eliminates cases of lubeKutorit. While the general medical <pision It that aluminum has bo effect one way or the other on taberoutosU, yet it u Most of the past year's outride laboratory research, and animal experimentation con cerning pur work, has been concerned with pneumoconioses other than silicons. The 1954 closing of the Trudeau Sanatorium, at Saranac%ske, Is one evidence of toe success of tuberculosis research. .37S . In Ontario, encouraging results are being Balmer Notify, and myself representing o&t&ined by the Department of Health is research <m the ose of "Killed Vok Vac cine** is place of BCG in immunisation against tuberculosis. That research was com- McIntyre Porcupine Mines, limited. Also included in the group were mine medical directors, Dr. H. Moore, of the HolHoger Consolidated Gold Mines, and Dr. W. D. roenced several years ago under the auspices of the minitig companies. Dr. D. A- Irwin, a Foundation Director, then of Banting Insti Robson, of the Melstyre Poreupme Mines. That particular silicosis session west a long way to consolidate Ontario's program tute, Toronto, did the early research* Of particular interest to the Foundation is animal research stated to be tinder way in South Africa. Theft nvos&eys, rabbits, and guinea pigs are reported under test by quartz dusting to produce silicosis and by aluminum dusting to prevent it. Results have not yet been reported. l9Si McTNTY*E-SARA}MC CONFERENCE of silicosis prevention through the coopera tion of the medical authorities and mine management. Outlined at that time for the purpose of studying prevention was the fact that silica (quartz dust) caused silicosis, with tuberculosis as a complicating factor. The preventive -measures indicated were engineering control of the silica by ventila tion and dust control and medical control of tubeccukjris by x-ray diagnosis--control The Seventh Foundation Conference was of contacts--sanitarium treatment. held jointly vrith The Saranac Laboratory on Feb. 7,8, and 9. Unfortunately Dr. !- was-unable to act as General Chairman, but The idea was suggested too that certain antidotal rode dust discouraged silicosis pro duction. The resultant follow-up by the Dr, Carey F, McCord substituted for him McIntyre Research team of Denny and Fob- very ably. son in cooperation with the Banting-Best The two organizations, having been en Institute, particularly through Dr. D. A. gaged in research along parallel lines, were Irwin, was the emergence of the discovery naturally anxious to pool their knowledge that aluminum was an inhibitor of the toxic and resources. action of silica in the test tubes and with Our opportunities as Canadian miners to rabbits. dip into the pool of knowledge afforded by The McIntyre Research Foundation de our connection in the medical profession veloped from such a beginning. recall out earlier experiences. Of the 26 persons present at the luadwon, Meeting in I33 at Toronto with the at kast 14 remain active in their interest in National Tuberculosis Association and allied silicosis prevention. Four presented papers bodies, out pioneers participated in a re and discussion at the 1955 Conference, in markable silicosis session, with the late Dr. cluding Dr, Riddell, f the Ontario Depart L- U. Gardner, of Saranac Lake, presiding ment of Health, who gave a paper in 1933, aivd presenting a paper. and Drs. Irwin and Franks; the former who Under the auspices of the Ontario Mining was former^ with the Banting Institute is Association, a luncheon was provided for the now the Medical Director of the Aluminum 9 medical specialists presenting papers on Company of America, and die latter is still silicosis and for 12 other Ontario physicians associated with the Banting Institute. Dr. from the Department of Health, the Uni versity of Toronto, the Workmen's Compen sation Board, the mines, and the BantingBest Institute, Dr. (Sir) Frederick Banting being among those present. Along with 22 physicians, four mining engineers went pres ent, namely, Mr. A. C. Bateman, of tire Ontario Mining Association, and R.). Ennis, 376 A. J. Lanza, present in 1933, was unfor tunately unable to contribute this year. The successors trf three others in that group. Dr. Schepers, Dr. Dworski, and Mr. Parfcfoson, also took an active part in the 19S5 symposium. Stlicosfe prevention is a long-time effort. There has been, however, since 1933, and 4 k*\VV*<**v ' ** :'* ANNUAL REPORT OPUiJNTYRBJ^^&ARClUPOVNDATlON . partiadarfy fc the put lOrjiw^orft^tSrf'ptbm v presented and published at proof of a drastic decease in the faaidmlAtii Anmal Cbofereoce. The papers of the <rf new cases of sLBcosis asd of taherak^V^iim Conference of 1955 win be published at oar inm Thai * also.* cmariafcfe*ia bound Proceedings, increase is the life expectancy of lime wbo > The Foaodattoo's basic interest continues have contracted feilioosu.- > rilkosis prevention. It believes that In 1933 the avenge age * ofWt'^B&fauun therapy has a place in that pro- three McIntyre miom, then dying each year . reattoa, must engineering control can suc- through aflkaaia, was 40 years. Now the `oeaafully remove aU silica dust from the average age at death of CWario a*=*pkere at PIaccs at aJ3 eases fe 62 year*-*a feemae la' Sfc i .'tea. That isnt \% sot yet. pectancy t 22 ye** fe ,}* ^ 22 yeutl Foundation also continues its interest We cannot, of course, project W die future-1*1 ** |imoconkes. such an iaewase ia life expectancy.' thus took forward confidently to many On the FotmdatkstY part,".itaeareb 'fjfr`Wual beasts from the Mclntyre-Saranac being continued fe^Carferencc aad to increased protection of case of tiK.Ujgt Long SeeBoo^ftpjert;^^*361 ^ afl woricer* in dust presorted at the;Mctaly>*S^ if. . Ancus D. Campbell, ----- ---- wi ..............................=*' ' ' B.A.Sc., M.E., Manager. , > ; kW ..-y V- " V . ivff?*' *i`; ' '.* i ,'vv.' ' . i * .rti>. + , *>\** % v* \ v.*'-. ** --V..VV *> f-i.'. - r'r* '. . ... -JV - ' r'.* >***.' 'i .. ... 9 INDEX .. . ?* PWdtfr workers. silicosis claims 6$ ftl'Wsu ui 87,88, 107 Actisdrte jpg Aorte silicosis from scouring powder 207 Adsorption oq quartz particles 259 Aging of wm dust Ahvtirt 243 Alvmwunv twxwfcydntt PACE 226 Aluminum prophylaxis effective** 62, 22!, 222. 250 (or experimental silicosis 224, 2X In a foundry 219 tn ceramics industry 243 to experimental silicosis 224, 230 is gold mining 248 technique for administering powder 221, 249 Alummco staining technique 2i7 217, 218 Ahudnosis 2Sj Afartloum, antidotal effect on quartz *swstratkc in tissoe 79 216, 217 Ahouinan coating on quarts {article* staining technique 216 218 Aluminum hydrate, powdered effect oo normal animals or tuberculosis preparation prophylactic action against quartz mhalaiaoa expercmsvts injection experiment 22S 229 258 226 230, 232, 234 232 230 Aluminum retained in lire- and spleen after injection in lungs alter inhahtk* Aluminum therapy cost early experiments effect oo tuberculosis oo soduks historical in a foundry in ceramics industry In experimental silicosis tn gold mining patent results 232 233 251 225 238, 2S1 252 224 219 243 224 248 2 221 therapeutic action against quartz inhalation experiment %-ea? dHfactice pattern Aluminum hydroxide, eoUo&J effect on normal animals ioh&tioa of reaction to quartz preparation 234, 237 234 226 22S 228 22& 225 Aluminum trihydrate Alveolar das* deposition Alveolar wait lesions Amosifc Ampbibole 226 22A 10 181, 196, 201 J8I prophylactic action against quartz infection experimeots therapeutic action Against quartz injection experiments x-ray diffraction pattern Aluminum metal powder amount used for therapy composition effect on normal animals os tuberculosis for dusting for ejection experiments method ol d^perwag preparation prophylactic action against quartz inhalation experiment therapeutic action against Quartz inhalation experiments 236 236 234, 235 234 226 22$ 221, 249 217 229 238 216 227 249 225, 227 232 232 2M 234 Anhydrite 21S, 324 Aaoxia and ear pulmonale ft, 9 Anthophyllite intratracheal experiment intravenous experiment 181, 196 313, 314, 320 313, 320 AnthracosSicosU infective processes 203 15 Aathracosis ^ changes in Wood vessels b dust nodules and vascular lesions in reactions in 1 263 13 13 14 Asbestos ^ 181 196 tn dust mixtures in industry 196 tissue reaction caused by 10-14 world production 4 Asbestos bodies, Ulcosis 3 196 II, 12, 14, 194, 196, 289, 347 71, 184 379 k.' , ,,%_* JUPSX -Asbestos worker* iSvecfor ia ksloo* to Mood vttsdi of oouocespational respiratory disease of pelmooary disability ki pulmonary function studies of x-ray studies of tAoe 10 11, 12 m 196 198 198 Asbestos)* and intercurrent pulmonary infection 198 and lung cancer and tuberculosis blood vessel changes in SS, 200 15. 88, 200 14 eause dianges bi vascular adventitia in 196 12 clinical picture 198 disability features sew in 196 14 mddeace 198 lung biopsy 27 mortality <fe 88, $9 named 84 nodules 13 ` perivascular reaction of 12 progression 196 x-ray pattern 197 Asbestosis bodies 197 Atheroma 12, 14 Atheromatous plaques 12 B Bagasses* Banket of Sooth Africa, composition 95 33 Beryllium granulomatosis Beryllium pneumonitis Beryllium poisoning criteria for diagnosis Beryllium sarcoid Beryllium workers alveolar walls in lesions io Wood vessels ol Biopsy of lung for diagnosis Blood vessel change* and age Blood vessel changes and infection Blood vessel teskm* Byssinosis mortality data new cases FACft 94, 173 94, m 172 173 173 10 IS 26 17 15 11-14 84,94 89 90 C Catkin! gypsum (See also Gypsum) 207, 324 analysts of frogs cl animals exposed to 334 biological effect 324, 326 comparison of airfcome and settled dust 330, 332 composition effect on animat lungs 324 324, 342 on human longs 207 so fiAemdosis 215, 333-338 experiment*/ studies cakintd msum alone 334-342 325, 526, 333 calcined gypsum and quartz327-j3i 337, 34ft protective action against quarts 327-334 quam content 207 tissue reaction to 14 Bahlosls, x-ray features Berylliosis blood vessel changes in long biopsy patch tests reactions fo Beryllium disability in personsexposed to in tissue Beryllium content of phosphor Beryllium disease ease histories classification recovery from renal eakitii in Beryllium exposure and fong cancer Beryllium granutareta 91 173 14 27 27, 28 U 172 178 173 175, 176. 177 175 177 177 174 13 Calcium silicate (See also Hydrous calcium silicate) 343 Cancer of long and asbestos and beryllium and radiation in chromsie workers' Carbon monoxide in mine air 88 174 100. 161 253 247 Ceramic industry control of sltkosH mortality statistic* ssficosi* claims Chromate workers, cancer in 342 65 65 253 Chromium affinity of lung tissue for distribution kt body tissues reaction with proteins and audeic adds 255 254 2S5 380 DtDBX Gireotiom comtxrtmds aad Usag <aa<* animal expertcols reaction with body tissues Otroatam io hmgs relative tocancer to exposure Gaysotik Coal mine* cellular deposits m perivascular lesion of Coal miners* pneumoconiosis and tuberculosis lesion mortality data SACK m 254, ts$ 2S3 254 254 181, W, 201 \\ II, 12 55, $6, 92, 202 206 II, 12 8$ Cristobalite cause of pseussococuosh td foundry dost perivascular changes caused by race 55 219 12 Criteria of disease 283, 28? Oecadotite IB1, 196. 201 Cutting samples 246 Cytobielogkai tnanrfeseatlons of surface proper* ties of quarts 261 D Dermatomyosltis Diatomaceous earth vneumooactiiKU changes la vascular adventitia In 17 n, 54 12 Cm3 mutiny, pulmonary disability associated with 202 CcnJ trimmers 202 Cobalt effect oa animal hangs inhalation experiment intratracheal experiment J14, 125, 158 117 U6, 117 Cobalt oxide effect os animal fungi intratracheal experiment 114, 122 ns ^lagest, deposition of 10. 17 2aJtofdal ahutomira hydroxide (See Afarminvm hydroxide, colloidal} 2ampensatioa accrued liability classification of disability coverage is Great Britain data on silicosis for disability medical boards 157 1S6 85 51, 65, 249 157, IS9> 160 160 or pulmonale and anoxia and wbesfosis and silicosis cod tuberculosis and vascular changes causative factor of death cause oC disability caused by emphysema is coal misers is tak workers xtiartropin, response with 8, 9 7. 198 7 15 16 1, 8 % 154 206 70, 71, if 17, 176,177 sniseme, response with 17, 176, 17? Differential susceptibility to dust Disability associated with coal mining basic concept compensation for partial for total evaluation h persons exposed to beryttiem in silicosis 283 232 459 159 159 157. 158 172 249 Dolomite, intravenous experiment Drilling methods 313. 314 166 Dost eoneentistioB in ceramic plant 2d Ontario mines Quebec mines in South Africa safoet la tak mines and mills permissible limits relation to silicosis 242 m 247 56, 46 67 50. 165, 247 49 Dust coitrol by ventilation k mecal mines 368, 369, 245 165*167, 246 Dust diseases in Great Britain, historical < DusA exposure, e&etUanecu* 83 91 Dust nodules and vascular lesions, relationship 13 Dust retention in lung 285. 286 Dust sampling method 247 f Emphysema and'bronchitis cause of cor palcoonale heart failure 84 154 S i 381 i *r-'-**;^>< : - V 2-it \> i ;,vTtf x-ki^-y -< ' *.H- '*'> ' ; ?... ^ ^ -v .. Bgpbynmi rorffimed focal Irons nn earth fiooride* la asbestos!* fe coal saber* . EffdeaJofegy of rilre**. earl? studies *Ate 77, 310 205, 310 198 Graphite pneumoccolosU Gypsum (See also C&ldoed gypsum) effect on human fangs oa tuberculosis quartz content tissue reaction to INDEX PACE 95 207 215 207 14 Etiology of riljrosii, cardinal factors Gypsum mines and mills, dust condition? 207, 208 Fanned* 2an< Fett/era *; * *. , Fibross* is ooal obe** beg* . Fluorescent hap verier* .' Foundry1, afllcori*central 2s . Fasdiy industry,e^ fa Gypsam workers analysis ei hreg tissue of autopsy cases hUtopatbology of ieskos of 209 208 209 11 H H-1010 powder (See also Aiuminnm hydrate. powdered) 225, 226 efiett no oansal animals 229 - Foundry worfee* \*` ft aJteoUr veflj . vlefcas* of.bleed iu4> of '* ;'^Ajet*d to ahimkieffi fcgipy ` ' m{': *> *;.;*Q''*'*A- '' . ''*:1 " *-j\ * ,\V- '. . Geothermal gradient *; ** ' GSus cettaa, effects ce inset 73, 170 27/ A * .-Kolctf*! *&''> v/.-* > ''.anpoafeba - /fv- v . .''deowwtntfioo fe time '. *.V; .' ' `effect* ee aafaai bags : ,*V. hhibtioa eaperiasat . '* fetratradseal esperinent / \ y tb* * . - , - V' --* , Gauwooi * ' Uokkal * '.. effect*ooeokolfoyt 275 . 272 280 271, 27* 273 272, 273, 277 271,275 271 275 27J, 275, 277 Gold mbers . <v* occupational dxat disease* fa * South Africa^ Gold --*"^g ^ 33 33 la Canada is South Mica 57, 245 34 Geveraer GenenT* Ccomliskm of Semi Africa / Grain dodw* gnewMuom 37, 38 95 Gnshe todnstry dSttthmm erftot control fT<iirminlok study aaortaiJty statistics . a-rv eaaariaatko dal* GeipMie atom. crffalsr deposits in 28? 50 49 65 52 11 Hamman RJeh syndrome \7, 31 Heart faifare, causes Hemibydf&te 6 207, 324 * Histo^asmosis 192 Hydrous caJdure silicate analysis oS lungs of exposed animals composition effect on animal tissue iohabtkfn experiment reacteoo of uninfected animals of tuberculous animals 353 343. 344 343 343 344 348 Hypertension is occupational chest disease 16 Industries in which silicosis occurs 86 Iniectioo and vascular abnormalities 15 Infection technique 325 Initalation technique 228, 325, 343 Injection techniques 228 Intraperitonea] technique Intratracheal technique 228 114. 228, 292 Intravascular tediniqoe 228 Intravenous technique 228 Iron, tissue reaction caused by Iron miners alveolar walls in cellular deposits in lesions of blood vessels of 11 10 11 n K Kanimeier sampling method 166 ; *}r. . , *' 4 INDEX ` *->-- K< i OceupatSonal chest diseases Leather dressers' poeamocoqfasts * 93 b gold miners V * l< ^ 4 - -fa negro laborers leg!sfation. pclmcrtary disability, of . ,, , f.. ha white miners' Sooth Airiea ~ "MS value of lung biopsy contioaed Long ash analysis * . Ontario mines, range of operations of goeoea pig* exposed to gypsum and quarts 334 of workers exposed to tremolite tale 183 *agi. rn ' 41 38 26 `l65 Liatg biopsy for diagnosis -technique results Long cancer and asbcstosls and beryllium and radiation in chromate workers 26 /, .. 26 ;...............27 88,200 174 ` 100, 161 253 Particle count relationships of air* boraedust Particle size distribution of dusts Patch tests far berylliosis Pathology, comparative vascular Periarteritis codosa Saipus erythematosus M ' 17 ..5-. u. cor- -c tx..1; z>-j. PhcnyShrine Plccral plaques Manganese poHjruoconitxi* - fpeenoaBHOsis Jiaximtim allowable concentration, slUzxrdigh?SOL, ^^and fsadttttWDia-'''' Meletyre-Kescarch Foundation directors history objectives report research work - **~*i' iujagt ,.,pod tMferoSosis- -- - reu fee, * titnkil'4kgsh .v. .. ,. - try. yez.?2 v.'(/3prnpewti<fa : : - ... ..oc; }; Z-. 374 3 ' from.vegetable.dusts.. miscellaneous dusts* ystoSSr* ^ *- Medical Boards ior compensation JSO in bofcr scalers Metabolic rate far various species 28? Meta! grinders mortality data silicosis data 89 88 Miners Acts of South Africa Miners consumption . . C '35,36 49 Miners Phtlusis Bureau of South Africa * 34 Mining Act of Ontario 56, 57, 165 In diatomaceous earth workers io grain-dockers m grapldte worker* is G{ea^jBritai& ^ .. in leather. wp?kers .,. . in ncm-ferrous.fQUBdry workers incidence on the Kollr Gold Field mortality-data .new cases on the Kolar Gold Field Mining methods in Ontario mines Mysore Silicosis Kates 168 73, 79, 81 pathologrtal diagnosis radiologfaM~<fiagneete *- 80, 356, 358 80, 284 27,28 7 ` .17 tl 243 212 81 79 74 81 250 94 91 83 92. 54 95 95 83. 89 93. St 77 89 88, 90, 91 73 76 75 73 N Pneumophor 243 Natioral Health Jn*rorance Act of Great Britain 85 tfodote of anthracosUkosis of dost diseases 2Jortfc Carolina, a-ray examination data 32 13 52 Occupations! chest diseases comparative vascular pathology of ? Potassium carbonate and quartz, biological action /-% 107 Pottery*wdrif* mortality''data silicosis claims Powdere4 d metallic aluminum (See Aluminum 89 65 metal powder) Predisposition phase 348 Proteinadsorption on quartz particles J 259, 261 383 je>Jisflpu| jo,;' zireft |*n? , 4 vwmrtX# O>l ppaaswo*uIw ssafltud eauufin8s pjo ssaSuurntjj jjuo ;'. . ''*> I?2 u,.;',ll.i,S,/v > ' wnmutnj* Su{Ajaj^$fetu|ue 30 sja) jo iirerracnjuo5a Bbajni(!S SUJrBja StSOOIjSS <8M*jJ0M Jpwq ttJffS m $i . . : svwmawanoud w sSurpuy |83i8oiwpsg 2QI '(4 * r 3uiH u`0Ji fc>cn?Kap 'isnp Aij3?ospe^ C9I $$ 9unj qi O) i)tui| ajqissiuuad uaouitxttu 2e$op uoiptpca sopijjed *cnb u4j paAjMsip scr snjjtMq JQ ufww > ',-$! " jo saime; Xsj-x Uj 8U01J3BS4 t , Xsdotq Iod^ .. iioi[ ppuasss ik 'csi `az sa;u>6o3d aasjjns ' ow : s*tittq> |ssa poojq * . 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C9 *9? `19! `66 IP juo|| ^qnsrmod nmiuixeuj Mim at aoqBgiowKi? oopey 19! 22V3 i}l}K}np Xj8aKB{B UOflT^s; pue ttVJtt AttWB^Otl r^-.>g;gk..gA < .aar*^*7^ .. ** `f**- gp ' XS0}0)euic4(!uL<s S8 uniMfi \t>t fiUOlfOqSF O} UJ$Bpi jo pjxog 1?PK sko)**isv Pu* stw*'!!1? 9 `99 fSr 59 52 59 081 'W `U "99 T!**111 SM `$C `iC '9C zj-x isaqo in siuspuy W s8mpuy on{<]ei8otfkrOipoi motsaj z$ It iwwuojouinsud3l*si bxjjv L{jnos sisp oojiBusiuiwa X*x tn suopBaj anssn Hiatt >ToudJOH> 02 `- saabjjd 3{X 6* 19 '6S `9S `Z* uopsijuwuoo inp ot wnsodxa jsnp jo uofi&lBp i 08t 9sm{ uo paga %snp Sunmu ojX 19 '65 ' `9C 9*B 0} UOi)Cj91 9 281 `181 31 u{ jsnp jo uo^gjitBOBoa isnpojd jo at >np jo ikwso<Juj<*> sflreo pvt ewwi of*x z* J9 '2* '6C 19 `09 `6C SC `a uoaBoytsrB^asj jo ootsirBiitojd jo wi*8> aw jo uoneogfirw jo ?lJ 9S28 3isis-ui jo uotitm at >jca ftl ut sjo^oa 8t XSojoqied Ajguotujnd oots$aiSoid I8t uoiitpuao np fgj ut u^qjow jo s9un[ jo jjsXjsue Xijsnpui o|*x Sie 'SI `C81 *11 181 * ~r* Slf 'CTC: SIC '*|f 'CtC 2IC *9 pns> uoipisaj wwsti ejyadoad juaurjjifcto sruxmsjjut juatuuadxa jo]otnBu anssij jatutwr u ijjo }MJ> oj*2 .561 `W `681 '*( 'C6 *|poq *(*l 2j j p^nvJ ucrjtrcsi ansst* `ilmcub pen 9jx 181 *081 ooHtsodenK* *spx X 192 . 1%Z 592 19C I9f 59 - euopttssjrusiu |&Ljk>|Ott]oio jsnp ziirtib jo otuadoid eprt^ iSu* ij wejjng ujt&fijfia j*3 sapiWEtJ ' ej?i[jtta Mi sd)sau8*8 omp s|ti uojonuqng |ajV VnS u! w" uO(l>npoad 88 'S9 `J9 `09 ts 't n*tm* ^ijvwoui IZ X5<j<q Vurt] St EOSfJJO/rf dAdMJOf zs saaitJOA juoiowA t 88*98 $insodx atuH^njo oo)$ u> TSl `W 't9 Z9 `9t 98 `ZS _ wujv sjwos w SM^JOM 3}tqS tR 99 73u9 eujts ut 88 `S uansodxa 2cmre(qj>u ut 6*2 `i9Z oacprtO ul 88 'Vi `99 Ansopu; Xuuod ui *9*85 OU|)UQ Ut *ZS 88 *99 98 W 'CS *25 fiMtjo* eatjoa'Q qvoM ut vsajnsodxa Sespuua jnoui Sio^jOA aao!wu3t| ut Xjltnpai auitnvaipr&iS ut 6W `85 aurans pjoS ut 6IZ *88 `28 `*9 'CS *K <Cflsnp! ! 51 </ jw f 2*2 >9 Xosnpiu ut C9 '95 speaeo w . 59. ,, *tu]*p stseoiji* *sj3jpu oooiS gg sjo^zoa iapod a&utuqe u{ ^01 spod auuncoi utoij |5 Xj-x `stioaues ut ua$ infz) ISC | status gp je)g paintrj ue xp<4$ 8o[onU3ptda ! ` 522 sjoaiuadx nojisjamij at s^jeap sooatntiuods IU y 0*C *03fi!S I *v>up 2s*l**lS rtJWb jo/Cjjitgnjo^ 9*2 SujqsnjS gj jpj *g5 fp 59 *jj 2i pg jV tjtaos at aap^rtq iiuioaow opwg> si t|op oopwu*iatoo ut spnuaApa XEjronw. at ssStrcHO XOtnpui ut jo asots 8K vretfStnoapuioistuuiS ut sa8ae{0 pooft 9 ' 16 'a OS $*2 2>2 612 moirortqwJTa tojopoo oj#J*S smsis vjwajd 'monoid stsootjjS Suiuttc p|8 ut XlQsnjnn otbjo> ui ijponoj ut tojiaoa srewfffS 52 so<]eMjiu 6*2 `<Z2 *88 *62 `C9 *19 `09 *8* V* 'BC ' *2 pso^aoj^M pux stuoumood pas sjMwttS o*c m &Z 30a ij<wp stnXjod ppe op?ttS XjijsQap* *p3 tJ`S --V fW- xaatrr *%>-- X^Vi **' s-- *../ INDEX Tak reaction, pulmonary *ACB 183 Tuberculosis--continued race Xafc worker# alveolar walla a composition of lung ash of lesson* of TakosU oud infection asbestos bodks in Hood vessel changes in uodoies reaction in Tntalua oxide effect'on animal longs m&atracheal experiment lli, M 115 m South Africa 34, 36. 38, 41, 44, 151 incidence is Oorgaara mine mortaftty rate tn Omario rate in omen of tri-state area therapeutic agents Tungsten effect os animal lungs intratracheal experiment 114. 132 US Tungsten carbide effe^^B aainal lungs inhalatiea experiment intratracheal experiment 114, US. 138 117 115, 116, 117 y TtfBperatures io mining . 73, 170 , * > UUramfcroscopie sINca, lesions caused by Tttfriwa decay series '100 Thorcc daughters, biological half life *< incit too pro' Uranium mines radRsctive elements in Trenwlite 181, 195, Wpk radon concentrations is .. intratracheal experiment intravenous experiment 313, 314, 516 313^ 316 ag V 10 160 162 Tnmolite bodies 11, 14, 195 Vanadium poetsBccontosia 93, 95 Tresnolit* pneumoconiosis ~ 71 Va4enla^ahnonnalitkg and infection !S Treraohte tale industry composition of dost 0i product pulmonary hUtepathology studies of lungs of exposed workers 182 181, \%2 183, 284 183. 184 Tridytrrite, cause of pneumoconiosis Trudeas Foundation, establishment of Trudeau School, establishment of Taberculositicosis blood vessels in tn Ontario m Sooth Afcwa 45, 63 'odS iS W 44 'll ,44, Vascutagehanges and cor pulmonale symptoms without raotgenogram changes 16 18 Vascular kstons and dust nodules, relationship 13 Vegetable dusk pneumoconiosis Ventilation i names ., . W 94 168, 169, 245 Vermont, x*ray examination d*.a 9 *w 52 Welders " aJrCOkr ^ " W. pneumoconfeis in Tuberculosis and asbestosis and calcined gypsum and coal miners' pneumoconiosis v,r appearance of lungs of 88,200 Witwaterarand gold mines 215 33 206 Workmen's Compensation Act of Great Britain 84 and silicosis 7, IS, 36, 37,38,44, 45, 48, 88, 220 death rates in miners definition 46 346 Workmen's 6&mpcnsatxon Board of Ontario 1,, 57 early experiments effect of gypsum on 5 JIS X-ray exanun&ion data of silicosis 52 i