Document g2akxZrLQ5mBNJzK40kZ4YR2L

FILE NAME Talc TALC DATE 1955 DOC TALC496 DOCUMENT DESCRIPTION Saranac Studies of NY State Tremolite Talc Arch Indust Health - The Effects of Inhaled Mining Dust on the Human Lung emr + e re a Pence: nn 2 SER Se, tes De RAS Samer Seana! The Efects Effects of Inhaled Talc Mining Dust on the Human Lung The extent to which the mineral talc is responsible for the changes in the lungs is G. W. H. SCHEPERS M.D. D.Sc. still in doubt Certainly the experimental and and : T. M. DURKAN M.E. Saranac Lake N. clinical evidence incriminating pure talc as the principal etiologic agent in called BIRR ee talcosis has so far been much less convincing than similar evidence supporting the views Talc belongs in the group of silicates that have been under suspicion for many years as that silicosis is caused by inhaled quartz dust or that asbestosis is provoked by inhaled a cause of pneumoconiosis The literature contains a number of reports of studies which indicate that industrial workers exposed to tale dust sometimes develop changes in the lungs and several investigators have used the term talcosis to describe the pulmonary asbestos fibers Nor is there complete cer- tainty yet concerning the pathognomonic fea- tures of the specific talc disease In spite of these uncertainties reports on-on- 21 clinical and roentgenological and 13 autopsy studies exist in the literature com- condition produced in those exposed workers mencing with the first paper by Thorelin Pure talc a hydrous magnesium silicate is a specific mineral but as Schulz and Wil- 1896. Jaques and Benirschke * have recently reviewed these cases The main emphasis ap- liams pointed out the word tale as used pears to be on a radiological pneumoconiosis in industry usually refers to a product which meets certain physical requirements rather ranging from diffuse bilateral reticulation 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 Schulz and Williams found that 51 samples of from a benign to a rapidly developing fatal process with emphasis on cor pulmonale as commercial tale the amount of the tale com- the cause of death There may be a prolonged ponent based on the count of particles smaller than 10 never exceeded 52 of the sample symptom induction period Tuberculosis emphysema and bronchitis vary in their Other prominent minerals in their samples prevalence Pathologically the condition has were serpentine dolomite and tremolite A been described mainly as a dense type of review of the data on 35 tale samples re- fibrosis with peribronchial and perivascular ceived at The Saranac Laboratory for routine prevalence and sometimes with nodularity analysis revealed that the composition varied Talc has been demonstrated in the tissues of widely In 8 of the 35 samples there was no . some cases and the suggestion has been ad- more than a trace of the mineral talc present and all the 35 contained a substantial amount vanced that the tale shows certain erosion changes in the human tissue not present in of one or more other components such as tremolite mica carbonates and clay min- erals the original state A point which has by no means previously been settled concerns the role of substances inhaled in association with the tale as the cause of the disease proc- Recorded for publication April 7 1955 Director Dr. Schepers and .Chief Chemist Mr. Durkan The Saranac Laboratory ess Speculation has mainly concerned the effect of the quartz which has frequently been demonstrable On the other hand cases 180 Re aka hoe wes. shears het qectin EES it niet Rees Poe oh BBE 2200 Jus neral tale is the lungs is rimental and pure tale as in called s convincing g the views quartz dust by inhaled mplete cer- comonic fea- reports on al and 13 ature comThorel " in ve recently aphasis apnoconiosis eticulation osis to con- ntly er- oping fatal monale as prolonged berculosis in their dition has ivascular type of ivascular dularity issues of been aderosion esent in has by oncerns ociation e proced the quently . , cases EFFECTS Of inhaled MINING DUST DUST have . exist in which neither quartz nor talc 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 talc lesions have been observed not only in the lungs but also in the pericardium the epicardium and the gastric mucosa besides surgical wounds It is evident that a great deal may yet be added to the sum total of our current knowledge con- cerning this 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 the tale industry of Northern New York State together with the chemical findings and histopathology of eight deceased employees from that same industry SURVEY MINES OF DUST CONDITION AND MILLS OF THE IN CERTAIN TREMOLITE TALC INDUSTRY OF NORTHERN NEW YORK The rock mined and milled in the area in Northern New York studied by The Saranac Laboratory although sold as tale is a mixture of talc and tremolite accompanied by a smaller amount of anthophyllite All three minerals are silicates The talc usually develops in thin flexible white laminae that are characteristically greasy to the touch but in some samples from this area it occurs in fine fibers instead of the usual plates The tremolite anthophyllite normally occur as coarse crystal grains but in the area studied * These cases are part of a series collected by the late Dr. L. U. Gardner A manuscript under preparation by Dr. Gardner had not been completed by the time of his death The present account is an independent study of the material without reference to this manuscript and elsewhere those minerals sometimes break up into long narrow fibers and then exhibit the structure and properties of asbestos It should be pointed out that the term asbestos does 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 chrysotile 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 varieties amosite and crocidolite Tremolite and anthophyllite are also members of the amphibole group Since the experience in South Africa shows that at least one of the asbesti- form amphiboles 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 tale which may be present in fibrous form might have a similar on tissue Representative samples of the mine product from three mines and of ground talc from two mills in the area were analyzed by chemical petrographic and ray diffraction techniques The results appear in Table 1 At the same time samples of borne dust were collected with an electrostatic precipitator in two of these three mines near a miner operating a jackhammer drill and in the working area of both mills Later precipitator 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 TABLE Composition of Mine Product and of Milled Tale from Tremolite TalcIndustry of Northern New York Mineral Mine Per Cent Mine Product = Mine Per Cent Mine Per Cent 9877-8 50 35 9877-8 9877-8 7 9877-8 5 987 -8 3 9877-8 10.1 Milled Talc Mill Cent 228 228 228 8 z r] Min E. Per Cent 5 7 6 2 02 MID D used the mine product of Mines B and C and MID E was supplied by Mine C. - _o . 181 me Pe Nana MM ATE DOM@R DM ee ae eG alt Se) we Pe are ny en Cok tha ARE, AX Drae re CA ee OH EE NS nae ae Ng SCRE Bit a TBI CALLS angieae Se x LE Cease SCHEPERS AND DURKAN Table Composition of Atmospheric Dust Collected with Electrostatic Precipitator in Mines and Mills of Tremolite Tale Industry of Northern New York Mineral Mine & Per Cent 0 13 60 : ) s 2 TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI Atmospheric Dust ves TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI TITTI * The two samples of atmospberie dust from Mine ^ were collected in different levels of the mine They were taken several months later than those from Mines B and C and Mills D and E. in the mine product and in milled talc This finding is in agreement with previous observations * that the composition of borne distributed throughout the entire tremolite tale bed but the analyses in Table 3 show that it can be present in substantial amount dust may differ considerably from that of Owing to erratic distribution the quartz de- the source material from which the dust posits may be missed by random sampling originated Even in the same mine there In attempting to take cognizance of the may be substantial difference in the com- potential pathogenic role which may be position of the borne dust one atmos- played by the quartz in the tale sight must pheric sample collected in Mine A had a not be lost of the fact that the quartz found quartz content of % while for another in the lungs of deceased miners who had also sample taken at about the same time but in worked in other industries may have been a different level the quartz value was only derived from exposures in those industries % Table 2 This variability in the quartz content is illustrated again by comparing the CHEMICAL AND PETROGRAPHIC STUDY OF analyses of various samples of rock mine- THE LUNGS OF EIGHT DECEASED product and borne dust taken in Mine INDUSTRY EMPLOYEES vy 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 % to 0.3 and in one miller from the tremolite talc industry aterw. the Mine B samples from 41 to % All the miners had been engaged in drilling 5S This matter of quartz content is men- rock for periods ranging from 10 months to Be a tioned in some detail first because previous investigators * have reported that they found 27 years The mill worker Case 3 had been employed for six years but as his body only a negligible amount of quartz in sam- had been exhumed for study 18 months Pi ples of rock and of ground material from after his death the findings are only of lim- this area second because it has been dem- onstrated Table 4 that at least some quartz was present in the lungs of one miner and ited value A portion of the autopsy material was taken for gross specimens and for histologic examination and the balance was one miller from this local industry who had no other industrial exposure to dust and reserved for chemical petrographic and ray diffraction examination For the com- third because quartz is a known pulmonary ponent chemical analysis and a few of the pathogen The quartz may not be uniformly mineralogical analyses samples of tissue Table Quart Content of Rock of Mine Product and of Atmospheric Dust from Mines & and B Quartz Content . . Nine A. Per Cent | Mine B. Per Ceat eo ai Ta com ~ Rock chips 4 ! 0... ccsecsescenseveceeceeceteeerereeevserees e AMtimnoespphreorduicct dust 4 ! oes cece sees votes se cseccteereeneeenece 4 ! ! ! ! ! | .- 182 te bet as, he Table Analysis of Lungs of Industrial WorkersWorkers Exposed to Dust in the Tremolite Tale Industry of Northern New York Autopsy Case No. 1 2 3 . 5 3 Right Left Ash per cent of dried tissue % 8.50 % 12.11 % 13.02 Numerals Quartz Mineral Constituents Per Cent of Asb cee neces eee eeeu eee eesemeenenee 7.5 11.9 ok Take ....... Tremolite Anthophyllite Feldspar Minerals pee 18 13 8 7 nee 20 14 4 eee eens Tr oe) Mineral Constituents Per Cent of Dried Tissue Quartz ooo Tak ..... cee ee ene ce en en sna sccceereceenene Tremolite Anthophyllite soon cee ne cc .........e . ccc sse c csc caw c nee ne Composent 5.8 1.0 Tr 2.1 Xt 0.9 St 0.2 8 Analysis Analysis Per 3333 3333 3333 3333 aoe Cent 0.6 13 1.3 0.7 of Ash 7273 7273 7273 7273 Sees a 7273 6 Right %% 6.47 d Left 5050 7.45 8.0 3 2 ~~ 3 OTE Freee Freee Freee oe Freee 827827 827 1--50 1--50 1--50 1--50 1--50 50 0.9 0 S % 5.725.72 2.1 19 : 7 aes 0.1 - 33 33 40.0 51.6 4.8 13 0.4 ... 10.5 61 3.7 13.3 15.8 3.2 8.6 1.9 ... 36.0 39233959 52.6 5.6 39233959 82 2 39233959 7.9 16.1 39233959 8.3 3.6 21 26.9 39233959 129 5.8 39233959 2.5 39233959 23 29.6 3.5 17.9 141 15.9 6.1 72323 3.A 21.1 6.0 17 0.9 1.3 72323 72323 2.0 72323 3.1 4.7 7.6 72323 8.9 8.8 72323 6.6 11.8 72323 none found were removed from representative portions of the lungs and mixed The samples were then dried overnight at 105 C and ashed in a muffle furnace Most of the mineralogical determinations were based upon other mixed portions of tissue digested with 30 hydrogen peroxide by the method of Sundius and Bygden* to avoid the alteration in mineral structure sometimes caused by dry ashing The results of the chemical and mineralogi- cal determinations are shown in Table 4 It should be pointed out that the values given for some of the minerals are only approxi- mate estimates The quartz content was determined by a special chemical and petrographic method and is fairly accurate but the values in the table for talc tremolite and anthophyllite may be somewhat above or below the true valuc PULMONARY HISTOPATHOLOGY ASSOCIATED WITH DUST EXPOSURE Though our series of eight cases appears limited we were particularly fortunate in having available for study such a diversified range of dust exposures and lung lesions Table ) At the one end of our scale we have Case 1 with but 10 months exposure to talc dust as a miner and 17 years general mining At the other extreme is Case 8 with 27 years tale mining exposure and 10 years general mining The associated exposures included service as miners of zinc lead coal and iron py- rites This helps to elucidate the essential talc reaction as the normal result of exposure to dust hazards in mines of the latter types is fairly well understood Our best fortune however for the present purpose is Case 7 a person who had worked 23 years only as a tale miner before dying from an unrelated cause without any inter- current superimposed pulmonary disease This case may therefore serve as a classical example of a talc miner pneumoconiosis Case 3 would have been equally valuable as this worker had been exposed during his six years of employment as a surface crusher man and mill sweeper Unfortunately the studies were not made until his body was exhumed 18 months after burial and so not much detail was preserved However it confirms certain essential points . FUNDAMENTAL PULMONARY TALC REACTION The primary reaction present in Case 7 consists of multiple irregularly shaped foci 1 to 3 mm in diameter comprised of virtually pure fibrocytic proliferation and macro- 183 Table Industrial Exposures Causes of Death and Pulmonary Pathology in Eight Deceased Tremolite Industry Employees Dominant Pulmonary Lesions Case 1 2 Dust Exposure Tale June . 10 mo Drilling ys Other Zine mine 10 yr Unykrnown Lead mine yr Iron mine yt Art ac Death ? 38 Canse of Death Cor pulmonale : pulmonale Tale Pneumoconiosis Fibrocelular with perivascular granulomatosis . Massive diffuse Abrocellulas Abrocellulas . . Silicosis Advanced alguse with hyalinization isolated nodules Diffuse with focal ~ Nu Infection ! Histoplasmosis 3 Surface --seeeenee 48 ? Diffuse dominant- NO Bazal lobes tuber- Crusher 238 - ly cellular perivascular culosis Sweeper 692 - ry 14 yr & Mine Drilling 16 yr - Zine mine yr 49 Tuberculosis pulmonala pulmonala Coal EL Cor 27 27 Ironmine yr Massive fibro- fibro- cellular Multifocal massive Abrocellular Massive confluent and multifocal Conduent and massive Abrocellular Chronie basal tuber- culosis with bronchogenic spread Tuberculosilicosis Tuberculosilicosis with necrosis _ 6 Mine t IT ST mine FT Pyrites Jr. acne 82 Tuberculosis Diffuse massive Abrocellular . Tuberculosilicotie * Tuberculosilicosis with cavitation 7 Mine : 23 37 teeee ST Nephritis with cardiac falluse Perivascular dis- crete focal : xQ . NO $ Mine 1 Mining 10 yr 60+ Congestive cardiac failure Diffuse Abrocellular Massive multifocal NDI apes 2757 phage accumulation The cellular deposit Prussian blue while those which lie among ug tends to be arranged in a stellate manner the fibrocytes may be losing their con- around medium and smaller blood ves- taining sheaths as the Prussian blue reaction sels Fig 1A There is fairly abundant visible pigment which either is found within isolated koniophores or seems to lie in the is fainter and more widely dispersed Many of the koniophores in the alveoli show this ; blue staining too interstices between the fibrocytes Some of The larger blood vessels trapped within er n these particles are brilliantly birefringent and may be present as spicules some of which measure 0.5...by 5 Fig 1B these foci do not show much deviation from the normal It should be clearly appreciated that the focal lesions appear as isolated . These characteristic macules are easily distinguished from isolated mature silicotic nodules which are also present Some of the latter possess a halo of cellular elements and are probably composite talc and silicotic macules in section only and really represent cellular sheaths accompanying the blood vessels for variable distances The smaller arterioles may show some endarteritis ob- literans and rarely a tale body may be found lesions Fig 4B embedded in the vascular walls The fibro- Elongated terminally clubbed bodies cytic infiltrate abuts directly on the vascular measuring 20...to 50 long and in no obvi- adventitia However there is no appreciable ous respect distinguishable from asbestos bodies are present in fair abundance Fig 7 mainly within alveoli where they tend to occur in clusters held together by koniophores Fig 8A A moderate number also occur among the fibrocytes and in these sites modification of the lamina elastica of 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 where there are fewer dumbbell types there are also more instances of degenerative changes The alveolar take bodies fibers embracing groups of fibrocytes rather than subtending individual cells Fig 24 Elastic tissue is absent from the centers of are generally stained intensely by means of the cellular areas Fig 4A 184 AND DURKAN Fight Deceased TT, ~ ection <a Histoplasmosis Basal lobes tuber- F. F. Chronic basal tuber~ exlosis with with decrosis ~ with cavitation wr im 81 Pat Lyeru, I Cwern nar e = ban + She. 5 ke ex. e Ase: a Rd re nt boa as t Thich lie among me their con- JS: an blue reaction : ispersed Many 7 an veoli show this Pe Le trapped within deviation from rty ciated as isolated ally represent the blood ves- idarteritis ob- may be found ls The fibro- a the vascular no appreciable ation lastica of the ation through developed down among ng stroma in- b of reticular ocytes rather Fig 2A centers of Au ; ) EFFECTS OF INHALED MINING DUST . . Fig Primary lesion tale mine dust exposure only .. perivascular cellular aggregation D power view showing massed macrophages and fibrocytes and tale spicules Fig Stroma of perivascular deposits of talcosis A reticulum supporting the macrophages and fibrocytes in the primary lesion with talc components only How quartz content in lung ash B collagen abundantly deposited with fewer cells thigh quartz content in lung ashi , 185 SCHEPERS AND AND DURKAN DURKAN or rer ar pasetwe en 0 erg Fig Perivascular fibrosis in talcosis A abundant fibrocellular reaction around vessel a Suet moderate quartz content in lung ash B marked collagen deposition with paravascular nodule Sme 6 high quartz content in lung ash oe oer gh Fig Parenchymai nodules found talcotic lung A dominantly cellular nodule with coe central amorphous change and tale bodies low quartz content in lung ash B hyalinized were whorled nodule with peripheral cellular reaction high quartz content in lung ash me Dae ot A Na oe z PS b> ES a aeA 186 eatnerbetrs FE a05mma * Lyne a , . ^>roundvessel scular nodule nodule with , hyalinized oc ERR GT MRS Oo MAL ER OT CTH oSa Cn G ", < EFFECTS OF INHALED MINING DUST At isolated sites focal necrosis has super- Lymphoid tissue is scantily present in the vened within the cellular areas There is no lungs and the granulomatous reaction ap- . apparent zonulation around these necrotic pears to avoid these foci almost completely areas or any tendency to collagen deposition though these granulomata may abut on such or caseation No suggestion of tuberculosis lymphoid tissue The hilar lymph nodes show exists and the cause may be ischemic in view hardly any hyperplasia and exhibit minimal of topographically evident arteriolar occlusion or luminar narrowing On the other pigmentation only No talc bodies are to be found However minute circumscribed sili- hand the histological features are highly cotic nodules are present suggestive of histoplasmosis The perivascular fibrocytic deposits tend not to invade adjacent alveolar walls in massive columns though large numbers of alveolar walls are moderately thickened owing to cellular infiltrates and this change is the more evident at the points of junction of individual septa At isolated points the alveolar walls are inclined to be thin but there is Many of the branchioles and some of the smaller bronchi are markedly distended and distorted and are the seat of chronic infiam- matory change without however any material impairment of the epithelium Fig 9B The latter indeed tends to be hypertrophic with goblet cells predominating The bronchial glands are also somewhat hyperplastic A little plasma cell infiltration into . only a slight tendency toward rupturing as alveolar spaces are inclined to be moderately reduced in diameter The resultant tendency to atrophic emphysema is most distinct toward the lung periphery devel- . Septal cells are not conspicuously developed and there is no evidence of macrophage or septal cell catarrh into the alveolar spaces Virtually no excessive collagen is present within these alveolar walls but a delicate reticular skeleton supports its center Elastic bundles are poorly represented and occur in a fragmented fashion among the fibrocytes Alveolar wall capillaries are occluded along some stretches where fibrocyte deposition is particularly but more generally the capillary circulation is undisturbed Columns of cellular reaction accompany the interlobular septa to the pulmonary pe- riphery thus producing a coarsely webbed sectional effect There is more collagen in these septa than elsewhere Fig 11B The pleura shows slight cellular infiltration and mild collagen deposition internally to the lamina elastica Numerous tale bodies may be found here and some can be seen to par- tially penetrate the elastica Superficial to the mucosa is evident but there is no collagen deposition The muscularis mucosae does not seem to be hypertrophic because its component columns are so widely separated However this is illusory and there is in reality fairly marked muscular hypertrophy Sometimes this is focal in distribution Fig 9A How effectively this muscular system may operate is left in some doubt in view of the patent invasion of the bronchiolar adventitia by fibrocytes at many sites as the peribronchial veins and arteries are Similarly invested by the proliferating reac- tion MODIFIED TALC LESIONS The basic lesion just described may be recognized throughout this series of cases though modified by the associated pathological processes induced by other dusts It is the more remarkable to note that the cellular proliferative phenomenon is present even in Case 1 where the history of dust ex- posure is as short as 10 months and persists in virtually similar form only in Case 7 with a history of 23 years of talc exposure but also in the instance of Case S. where there was a year exposure history together with 10 years exposure to dusts the latter a vascular zone of fibrocellular re- encountered in zinc and lead mining action of variable thickness is to be seen There may be a greater tendency toward Isolated silicotic nodules occuirn this zone the formation of massive lesions and sub- It is covered by mesothelium Fig 12 pleural reaction where there is an associated 187 = + . ~ betas vore ~* KS . TS . TOES GATS tes BIS coand lence nee * g EV . . ep NIT im Ry kk Atcinae ,, sant ay A i May * = ws a f a ao alti he dapoih Fig Parenchymal cellular deposits in tale miners A loose cellular web with atrophic * alveoli moderate quartz content in lung ash B pigmented staining stellate cellular deposit ~ moderate quartz content in lung ash - Fig Stromal reactions in talcosis A pigmented fibrocellular granulation tissue with atrophic alveoli moderate quartz content in lung ash B. dense diffuse fibrosis with surviving elastic skeleton of occluded blood vessel high quartz content in lung asi~- be 188 Beppo} " [ ee ae ae Oe ' Se Oey 9 ae,on os e atropilic r deposit * with arviving Fig Tale bodies in human lung tissue A. slender elongated taic bodies emberkled in fibrous tissue B short dumbbell body partiy engulied by a macrophage and showing intense iron staining . . Fig Talc bodies in human lung tissue A. accumuiation of koniopivres sinewing a high Pa degree of iron staining and containing short lengths of talc fibers B tzic vody ameng eryturo- : cytes within the lumen of a bicod vessel . te ve " ; %og B wena, fe ete ere ts oe me. os. emce etn ee ee ee e Oe 00 SCHEPERS AND DURKAN quartz reaction In Cases 2 and 6 collagen formation is restricted to a minimum and the supporting stroma tends to be of a reticular nature of variable density In Cases 1 tially then there are three cortical zones viz a fibrocellular internal component which.. may be variably pigmented and which may contain distended bronchioles an intermedi- 5 and 8 there is a greater tendency toward ate exaggerated lamina elastica and an ex- collagen formation It is to be noted that of ternal highly vascular fibrocellular layer usu- these cases Cases 1 and 5 yielded a relatively high value for quartz in the lung tissue but ally covered by mesothelium Fig 12B The parenchymal stroma is considerably Case8 showed a very low quartz level Bire- fringent quartz particles are a prominent fea- ture of the tissues in Cases 1 and 5 and are exaggerated in the presence of a quartz reaction superimposed on the talc phenomenon Fig 5 This is largely a perivenotis but poorly demonstrable in 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 exposure and there is consider- incorporated within the scars as to be- able collagen deposition even with some hya- trayed only by their residual elastic tissue linization in Cases 1 2 5 and 8. Indeed in these cases the alveolar wall involvement is so pronounced as to overshadow somewhat the skeletons Fig 6 Vascular damage is indeedvery much more in evidencein those cases with the long- essentially perivascular distribution of the est history of rock mining or where the , underlying talc reaction highest silica content was discovered The damage sustained by the alveolar walls is further modified by the presence of quartz present Two essential processes are namely an endothelial proliferationin the least vesendothelial particles which involve marked macrophage and plasma cell infiltration marked enlarge- sels ending endarteritis or endophlebitis obliterans and a periarteriolar fibrocytic pro- ment and proliferation of the superficial sep- liferation with fibrotic stricturing or partial tal cells often associated with cellular catarrh invasion of the muscular coats Figs 2B into the alveolar spaces and finally moderate 3B 10 11 This process is present in its to marked impairment of the capillary circulation through these alveolar walls The latter most exaggerated form in Cases I and 6 in which multiple periarteriolar granulomata is not however a constant phenomenon and there may be advanced alveolar wall disease without appreciable loss of capillaries e g may be found Such lesions cause marked pulmonary ischemia the more so as the lesions are not limited to the pulmonary circu- Case 6 lation but may also involve the bronchial collagen present When is it fails to be arranged in the form of silicotic nodulesin all but rare locations e g Cases 1 and 5 vascular system at numerous points thus effectively precluding establishment of any collateral circulation Incipient fibrous whorls are present also in While the essential reaction to talc ap- Cases 2 and 8. Some lie against blood vessels pears to include exaggerated distention of Fig 3B It seems possible that the abundantly cellular tale reaction is incompatible with the complete evolution of the nodular silicotic lesions bronchioles and smaller bronchi this change though present in a variable degree in all cases of the present series is not universally . observed throughout the lungs where reac- Subpleural 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 tale and quartz have been considerable ing of the bronchial lumen epithelial desqua- The resultant lesion is howeanvee xar g- geration of the primary talc reaction except for the greater prominence of the collagen where quartz is abundantly present Essen- mation mucosal hypertrophy sometimes _. with papilloma formation and inflammatory infiltration with adventitial fibrosis and cicatrization at multiple sites where exposure 190 She ot ares de od aod 1 ON OW chat cor zones -- --whi--ch nd which may an intermedi- a and an ex- ~-larlayer usuFig 12B considerably a quartz reac- : phenomenon a perivenous ir columns of xluded blood so effectively as to be be- elastic tissue very much with the long- or where the discovered ent namely he least ves- ndophlebitis rocytic pro- gn rtial Fig 28 esent in its 1 and 6 in ranulomata se marked as the le- nary circu bronchial ints thus nt of any , t^le apention of is change ee in all niversally ere reac- present narrow- tea I desqua- metimes x} nmatory Se sis and xposure citvetyd ths: Fig Bronchial damage in talcosis A. irregular focal proliferation of muscularis mucosae low quartz content in lung ash B submucosal fibrosis with lymphatic distention but no injury to the epithelium moderate quartz content in lung ash Fig Vascular damage quartz content in lung ash . content in lung ash in talcosis B. talcotic d perivascular fibrosis and intimal swelling high nodules in the walls of blood vessels low quartz : Sug Tete 2 he, he aes SCHEPERS AND DURKAN to quartz dust was adequate This combination of chronic hypertrophic bronchitis obliterative bronchiolitis and the peripheral bronchiolectasia superimposed on the fibrocellular 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 tuberculosis or tuberculosilicosis There is some changes throughout the lungs may lead on the one hand to extensive areas of partial atelectasia of the relevant lung fields or on the other may be associated with the develop ment of multiple epithelium peripheral cysts The latter are essentially ballooned tendency toward inflammatory reaction at the periphery of the lesions in the latter three cases only On the other hand the necrosis also involves the stromal elements favoring histoplasmosis once more In the majority of other cases it seems possible that the necrosis terminal segments of the respiratory passages and may be readily distinguished from emphysematous bullae by the presence of the epithelial lining the residual basement membrane and the irregular presence of support- may be explicable on an ischemic basis either because the cellular hyperplasia had outstripped its vascular supply or because the latter had been cut off through regional vascular occlusion . However as all these cases ing muscle fibers True emphysema is rela- tively infrequently seen and when present consists of the atrophic vesicular variety _ The differential involvement of lymphoid tissue in the reaction to tale dust and to tale dust combined with quartz dust is clearly demonstrated in the present series Whereas came from the St. Lawrence Valley area at the time of an epidemic in that region it is possible that histoplasmosis may be a factor The process seca in Cases 4 5 and 6 if tuberculous has been modified considerably by the abundance of fibrous tissue and cells A large walled cavity without a dis- the tale reaction tends sedulously to avoid the tinctive fibrous capsule or even components lymphoid tissue the contrary condition pre- is present in the latter instance Atypical vails when quartz is abundantly present or where there is an associated tuberculosis tubercles are present within this wall at the edge of the broad inflammatory zone While Talc bodies are however never seen in the the temptation exists to interpret this cavity lymph nodes and the reaction present in most instances is limited to medullary macro- as tuberculous it may represent merely a chronic discharging abscess The lesion is phage infiltration and pigmentation Silicotic or tuberculosilicotic nodules are present in also compatible with a diagnosis of histoplas- mosis Attention may also be drawn to the but a few instances Cases 1 and 5 Despite marked peribronchitis and ulcerative bron- the fact that multiple nodules and necrotic chitis in the passage draining this cavity No foci are present in the lung substance the tubercles were observed here hilar node involvement is not marked This Pneumonic areas were observed in the state of affairs is the reverse of what prevails cases with exposures to both quartz dust and in the presence of exposure to quartz dust tale dust especially Cases 2 and 4 but not unaccompanied by an exposure to tale dust where only tale dust was the responsible etio- One is consequently inclined to infer that the logical agent This pneumonic process tends simultaneous presence of talc dust and quartz . to show healing by organization in various dust in the lungs militates against the trans- stages of progression and numerous tale portation of the quartz dust to the hilar nodes bodies are thus trapped It seems likely that Alternately though talc bodies are not seen in the hilar nodes their liberal transierence is those present in the formed lesions may have been incorporated in this manner through not yet precluded and the inhibitory tendency of the talc on the silicotic reaction which is earlier episodes of inflammation .. - manifest in the lung substance of this series COMMENT ; may prevail also in the lymphoid tissue The chronic or term effects of the Necrotic foci were observed within the . inhalation of dusts such as are generated in areas of cellular proliferation in Cases 2 4 talc industries are thus demonstrated by this 192 BS | wet CMRAVES 8g Pw tka Ane ae ieee fae EEF yh dpe GO Ly OUR CM fotos aby DS te mest ND DURKAN lasn is the Ees 4 , and 6 ive of tubercu- There is some reaction at the he latter three id the necrosis ments favoring the majority of at the necrosis ic basis either asia had out- or because the 1 regional vas- all these cases Valley area at t region it is y be a factor , 5 and 6 if considerably que and cells ithout a dis- components e Atypical : wall at the one While t this cavity it merely a he lesion is of histoplas- awn to the ative bron- cavity No ted in the tz dust and 4 but not asible etio- cess tends in various trous tale likely that may have : through tala BSat? Ti ro Y erated of the by d d by this by dj Sa eine f SPT <TS : Fas Sages: Sees Rtas lumen through Fig Vascular damage in talcosis A. progressive loss of venous pro- gressive proliferation of intima moderate quartz in lung ash B fibroelastic scar in interlobular septum representing the remains of obiiterated blood vessels moderate quartz in lung ash series of cases to vary considerably according to the extent or nature of associated dust in other industries to which the person may have been exposed either preceding or suc- Fig Pleural damage in talcosis A. diffuse fibrocellular partly pigmented and highly vascular reaction low quartz content of Jung ash B. loose fibrous proliferation external to lamica elastica with whorled nodule talc plaque high silica content of lung asin ~~ wee eS RW eq eee by ay, ys i SCHEPERS AND DURKAN 4 cn 119145 i 119145 119145 seeding 119145 the period during which talc dust fies appreciably the type of reaction to the was breathed quartz dust Though considerable quantities kakak The histopathological features enumerated of free demowenresdtemronastbralblee in the lung are almost entirely explicable in terms of the tissue Table 4 in some instances Cases 1 mineralogical analyses of the lung ash pre- 2 4 5 and 6 there was not in this series a kkaakkaakk ka k sented in Table 4 kakak clear tendency to nodular silicosis kakak Itis seen forinstance that for both of our Tuberculosis or histoplasmosis may have kakak key cases of pure talc pneumoconiosis Cases been a factor in the pneumoconiotic reaction 3 and 7 the quartz content of the lung ash in some of these cases While doubt persists 2.3 and 3.2 was about the same as as to the diagnosis of a true infective process uk . seat the corresponding value for many normal it does seem certain that if the latter diagseat persons never exposed industrially to quartz nosis has to be accepted the presence of the vo r dust Among this series the amount of lung ash of Case 7 is particularly low 4.69 of talc reaction induced an aberrant type of chronic inflammatory process dried tissue and so is the total silica con- While it has been postulated that the fore- m^/r tent 17.9 of ash which includes the silica going observed deviations from the primary BE in the silicates present in these tissues process may all be due to coincidental quartz Quartz was present in Cases 1 2 4 5 exposure to tuberculosis or histoplasmosis or compatible and 6 in concentrations *with nodular silicosis Indeed the average quartz to nonspecific pneumonia reference should be made to the fact that there is insufficient te content of the silicosis cases studied The knowledge in the present instances concern- 8 mentsohne't Saranac Laboratoryis 9.3 of the lung ash ing the differences in the talc dusts to which omen Cases 1 and 5 therefore had unusually large the men were exposed or to the concentra- amounts of quartz dust lodged in their lungs tion and rate at which the tale dust was de- aeons Yet nodular silicosis was conspicuous by its positedin their lungs The latter factors alone PoyiteSeb! absence in Cases 2 4 and 6 and only sparsely are known to influence the nature of the sili- Eno present in Cases 1 and 5 cotic reaction which may follow exposure to semeOboe Attention is drawn to the demonstrated quartz dust and the precise composition of ein presence dren of talc tremolite and anthophyllite the tale may therefore necessarily be a factor eret wal in the lung ash of Case 7. Thereis no appar- too In this connection it is interesting to eae ent correlation in this series between the note that the majority of tale bodies were in ata Pete length of exposure and the concentration of a range of 20 to 50 being somewhat longer these minerals in the lung ash eee 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 tale dust is the abundant also present Terminal clubbing was a factor amount ofquartz dust coexistent with the talc 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 tale employees had been miners also seen Segmented forms were but rarely seen of lead zinc or pyrites Attention is drawn In all cases mantle of the body showed an to the minor differences in the mineral components of the lung ash While we do know that quartz is an active pulmonary patliogen intense staining reaction but degenera- tion of this coat was demonstrable in most cases where the talc bodies were present in we do not yet know whether the additional the newly formed fibrocellular tissue substances demonstrated e g feldspar are capable of playing a material role in modi- " fying the response to either the quartz or the talc or are themselves pathogenic It does seem permissible 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 birefrin-gent particles spicules and crystals within the interstitial tissues and in the koniophores trapped within alveoli The variable abundant 194 ND URKAN reaction to the rable quantities ble in the lung inces Cases , in this series a silicosis osis may have oniotic reaction : doubt persists fective process he latter diag- presence of the errant type of i that the fore- n the primary cidental quartz toplasmosis or erence should is insufficient inces concern- lusts to which he concentra- dust was de- fa alone re or the sili- ' exposure to mposition of y be a factor teresting to dies were in ewhat longer ies generally tances some 200...were was a factor and 3 and ad could be rarely seen showed an t degenera- ble in most present in ssue es and the here were in tals within oniophores '" ndant EFFECTS OF INHALED MINING DUST presence of such elements at sites of maximal fibroid or cellular reaction may undoubtedly bear some relation to the differential patho- logical effects observed in the present series The pigmented particles though present in all cases were most abundant in Cases 1 3 6 and 8. Brilliantly birefringent particles on the contrary were conspicuous features mainly in Cases 2 3 4 and 8 and in this series large numbers of such particles were dispersed among the fibrocytes comprising the pulmonary lesions These particles were identified as talc . The talc bodies described may be an indi- cation of the main pathogenic agent in the present series of cases or may be merely incidental features Were the former to be the case it would perhaps be advisable to rename them tremolite bodies They were relatively sparsely represented in Cases 1 6 and 8 and it is interesting to find that in these very three cases the tremo- lite content of the lung ash was least They were present in greatest profusion in Cases 3 4 and 5 and once more the mineralogical analysis confirms the relatively high incidence of tremolite in these three cases Table ) The anthophyllite values on the contrary do not correspond with the histopathological findings It may therefore be fairly safely inferred that the tale bodies are of tremolite origin In view of the fundamental similarity be- tween the talc reaction seen in this series and the histopathological changes present in asbestosis one is constrained to speculate whether the tremolite component being an asbestiform mineral is not after all the main source of mischief It remains for animal ex- periments to shed some light on this subject SUMMARY A survey of the tale industry in Northern New York State revealed that the tale mined . and processed there consists of a mixture of talc tremolite and anthophyllite Quartz is also present in moderate amounts in the dust generated in mining and processing the com- mercial talc Lo A mineralogical analysis of the lung ash -} from eight deceased industry employees revealed the presence of appreciable quantities of talc tremolite and anthophyllite Quartz was present in significant amounts only in the cases where the men had been additionally exposed to dust in mining industries other than in the talc industry The histological features suggest that tremolite may be the main pathogenic agent in provoking the characteristic tale lung lesion The role of talc and of anthophyllite has not been wholly excluded ; The presence of quartz modifies materially the nature of the talc reaction The presence of tale dust in the lungs modifies both the responsteo 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 bronchiolectasis are associated major findings in this series The chemical analyses presented in Table 4 were made by A. J. Redlin chemist Saranac Laboratory E. S. Larsen 3d Ph.D. of the U. S. Geological Survey formerly petrographer of The Saranac Laboratory made the petrographic and ray diffraction analyses REFERENCES 1. Schulz R. Z. and Williams C. .: Com- mercial Talo Animal and Mineralogical Studies J. Indust Hyg & Toxicol 24:75 1942 2. Thorel .: Die Specksteinlunge Beitr path Anat 20:85 1896 . 3. Jaques W. E and Benirschke K Pulmo- nary Talcosis with Involvement of the Stomach and the Heart A. M. A. Arch Indust S 451. 1952 4. Hatch T. and Moke C. .: Mineralogical Composition of Borne Foundry Dust J. Indust Hyg & Toxicol 18:91 1936 5. Siegal W Smith A. R. and Greenburg .: Dust Hazard in Tremolite Talc Mining - Including Roentgenological Findings in Talc a Workers Am J. Roentgenol 49:11 1943 6. Sundius N. and Bygden A Isolation of Mineral Dust in Lungs and Sputum J. Indust Hyg & Toxicol 351 1938 195