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FILE NAME: Talc (TALC) DATE: 1957 DOC#: TALC096 DOCUMENT DESCRIPTION: Book Excerpt - The Physics and Chemistry of Dust annual review of medicine D A VID A. R Y T A N D , Editor Stanford University School of Mediane W ILLIA M C R EG ER , Associate Editor Stanford University School of Medicine VOLUME 8 1957 annual REVIEWS, INC. PALO ALTO, CALIFORNIA, U.S.A. nificance, lie others rise to the classical :ent of only a few ree silica, produces a result of the high ollagenous fibrosis, nfection (24). The film on the surface (25). _ ganister bricks to ainly clay; neither n this occupation, interfered with the or the exposure to al silicosis amongst ave been described liosis and showing iners. The average was very different pt when the lungs it some of the airthat the presence ant as it could de>ly the aluminium admixture of shale n its solubility. ble to inert dusts nstituent of which we come to cases ihemical combina n enormous num:oniosis have been mstances are too lief difficulties are n free silica along complicates the osure to dust, alline silicates in sed in various in cates as colloidal iresent in crystal- THE PHYSICS AND CHEMISTRY OF DUST 327 China clay, or kaolin, is a degradation product of granite and consists of up to 25 per cent of free silica mixed with hydrated aluminium silicate and traces of other elements. A post-mortem examination of a man who had lon g been exposed to ball clay dust has been described by Thomas (2 9 ), who found silicotic nodules which were less whorled than is typical and had taken a very long time to develop; another case, also of long exposure, is given by Bastenier (30). A survey of 31 pottery workers by Chiappa & Ferri (31) disclosed only a relatively benign silicosis. The exposure of rats to the dust by intratracheal injection of saline suspension by King et al. (32) revealed only phagocytosis with no fibrosis within periods of 60 to 161 days. The free silica content of the kaolin was not determined, but the silica solubility was very low. It seems that kaolin is definitely not responsible for a fibrous sili cosis, like quartz, and that cases in which fibrosis has been observed are a result of tuberculous involvement (30, 33) of lungs heavily charged with dust, or to the presence of quartz with its action modified by the kaolin which does not, however, inhibit the growth of fibrous nodules. The comparative freedom from silicosis of men in the brick and tile industry, handling china clays and fireclays containing free silica, is com mented on by Uytdenhoef (34). They inhaled dust containing 11 to 46 per cent of free silica in concentrations up to 700 particles per cc. He suggests that the concentrations might have been below the danger level or that the aluminium silicates had an inhibitory effect. Size-selective sampling with determination of free silica in, the respirable fraction should have been em ployed. _ Deaner (35) describes silicosis in fireclay miners with histological exam ination of one case. The man had worked for 23 years as a fireclay miner in a colliery where the clay was adjacent to the coal seam. The clay was mainly aluminium silicate with only traces of iron, calcium, potassium, and sodium, but it contained a substantial amount of free silica. Laminated fibrous nodules of classical silicosis were present in the lungs. The occurrence of silicotic nodulation in this case and that of Thomas (29) argues against a specific inhibitory action by colloidal aluminium silicate which appears, on its own, to cause an inert dust type of pneumoconiosis. Fuller's earth, another clay, is a hydrated alumino silicate containing iron. It has been reported as causing pneumoconiosis (36, 37, 38). Quartz was present in these cases, but the disease differed from classical silicosis and and took longer to develop. The dust contains 50 to 60 per cent of combined silica, i.e., SiC>2 in silicates. A number of cases of silicosis, diagnosed by chest x-rays, are described by Rombola & Guardascione (39) in the bentonite industry; there had been very heavy exposure to dust. This clay is mainly montmorillonite; it con tains a trace of quartz along with 32 per cent of amorphous silica plus beta- cristobalite. There were no post-mortem findings to indicate whether the disease was correctly described as silicosis, exemplified by the classical nodulation, or whether there was diffuse fibrosis and to what extent. The maximum exposure was seven years. A dust containing 32 per cent of free 328 DAVIES crystalline silica, inhaled in the concentration and particle size described, would normally have been lethal in this time. Peretti & Occella (40) suggest that the fibrogenic action of quartz is en hanced in the presence of certain clay hydrosilicates. There appears to be no evidence for this statement, either on physical, chemical or clinical grounds. The rapid onset of silicosis leading to death within a few years, which was common in the days before precautions were taken, among men quarrying sandstone, shaping it, or grinding upon dry sandstone wheels, has no parallel in the exposure to silicates in clay or crystalline form, even when an appreciable amount of free quartz is present. The evidence is towards a diminution of the activity of quartz, attributable rather to the presence of an inert diluent than to specific inhibitory action. Pneumoconioses caused by inhaling dust from clays are essentially slow in developing, even under quite dusty conditions. Occella (41) has analysed many industrial clays and has found free quartz present in proportions up to 50 per cent. This figure did not always provide a good index of the hazard likely to be attributable to the material, because a low concentration of quartz was often associated with a high pro portion in the finer particles, which alone were small enough to be retained in the lungs. A survey of the cement, clay, and pottery industries by Sayers et al. (42) showed the main hazards to be the well-known ones attributable to silica and lead. A study by Parmeggiani (43), based on mass radiography of workers in the cement industry, proved that the highest incidence of pneumoconiosis was amongst those employed in mines and quarries where raw materials were obtained and cement dust was absent. Few workers in the factory where cement was made showed more than slight lung shadows. This was confirmed by Giulani & Belli (44), who x-rayed 180 people working in a cement factory and found no cases of silicosis, although 20 per cent of them gave indications of inert dust deposits. Upper respiratory disturbances were prevalent con firming that industrial hygiene practice should not be restricted to eliminat ing fine, respirable dust. Russell (45), also, observed the tendency of cement dust to cause bronchitis but found no encouragement of tuberculosis and only slight pneumoconiosis. Experiments in which rats inhaled dust of Portland cement containing less than 1 per cent of free silica revealed no fibrotic changes (46). Miller & Sayers classed Portland cement as an absorptive dust when tested by peritoneal injection, since the initial lesion dispersed and the dust disap peared (103). N onfibrous Crystalline Silicates Passing on to the crystalline silicates, several papers have been published on exposure to dust of the felspars. These comprise two similar groups of hydrous alumino-silicates of alkalis and alkaline earths crystallising isomorphously in monoclinic and triclinic forms. a to Experir in saline, IV than quart three kinds with time 1 nique was & J otten (A potash fels Rotter tuberculosi more widel collagenoui cent of qu aluminium solution, h Granite mica; it cc with nodu! tendency 1 tion is proj but a muc quartz dui granite wo A survi per cent f siliceous) granite m; without ini portional t In Frai granite du cent of fre German gi sis was ca menting w granite du; however, < did not pri Kaolin kaolin, fel; produce sij silica. It is minerals i: that fibro dusts and The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U.S. Copyright tide size described, don of quartz is en- here appears to be hemical or clinical .vithin a few years, taken, among men idstone wheels, has ne form, even when idence is towards a to the presence of moconioses caused loping, even under nd has found free ure did not always fie to the material, ;d with a high prough to be retained y Sayers et al. (42) liable to silica and graphy of workers of pneumoconiosis ere raw materials the factory where 'his was confirmed 1 a cement factory n gave indications :re prevalent conricted to eliminatndency of cement tuberculosis and ement containing ges (46). Miller & when tested by i the dust disap- /e been published similar groups of crystallising iso- THE PHYSICS AND CHEMISTRY OF DUST 329 _ Experimenting by the intratracheal injection into rats of dust suspensions in saline, Mohanty et al. (47) found that felspar was very much less fibrogenic than quartz. Policard & Collet (48) confirmed this work; they compared three kinds of felspar and obtained varying amounts of fibrosis, increasing with time but always less intense than was produced by silica. Their tech nique was the intraperitoneal injection of saline suspensions. Klosterktter & Jtten (49), using intratracheal injection, found only slight fibrosis from a potash felspar; hornblende, another complex crystalline silicate, gave none. Rotter & Grtner (SO), describing a fatal human case with extensive tuberculosis, state that the nodules were not like those of silicosis, being more widely disseminated; there was also less increase in reticular fibres and collagenous tissue. The dust inhaled by the victim contained 38 to 45 per cent of quartz with many particles smaller than 5 /i; they supposed the aluminium, potassium, sodium, and calcium ions, which would leach out into solution, had exerted a neutralizing effect. t Granite consists of about two-thirds felspar with one-third quartz and mica; it contains small amounts of iron, magnesium, calcium, etc. Silicosis with nodulation is produced in men exposed to the dust, but there is more tendency to diffuse fibrosis than with straightforward silicosis. The condi tion is progressive and associated with tuberculosis, which causes the deaths, but a much longer exposure is required than would be the case with pure quartz dust. These conclusions were reached following exhaustive studies of granite workers in Vermont (51, 52). A survey of 355 stonemasons in Australia who worked on sandstone (90 per cent free silica), granite (30 per cent free silica), and limestone (non siliceous) revealed seven cases of silicosis in sandstone workers and one in a granite mason. Seventy-nine cases of moderate, diffuse fibrosis were seen, without incapacity, and the amount of lung damage was judged to be pro portional to the free silica content of the stone worked (53). In France exposures of up to seven years to very high concentrations of granite dust, produced while tunnelling through rock containing 18.4 per cent of free silica, failed to cause silicosis (54). Surveys of the Austrian and German granite industries led Rhrl to conclude that compensatable silico sis was caused only after breathing the dust for many years (55). Experi menting with rats by intratracheal injection of saline suspensions of Cornish granite dust, King etal. produced focal nodulation in 100 days. The nodules, however, contained only a tangled reticulin network without collagen and did not progress up to 250 days (56). Kaolin is derived from granite, and reviewing the evidence relating to kaolin, felspar, and granite together, it is fairly clear that these substances produce silicosis when inhaled as dusts by virtue of their content of free silica. It is also very doubtful if any inhibitory action can be ascribed to these minerals in respect of the fibrogenic property of free silica. There is no doubt that fibrous nodulation in human lungs results from the inhalation of the dusts and that the aluminium silicate which they contain does not prevent - 1 330 DAVIES CD it. Some degree of modification of the nodule, the presence of diffuse fibrosis, and the long duration of exposure required all seem factors which can be accounted for by the dilution of active siliceous dust by inert silicates. A method of assessing the silicosis risk attributable to dust made from a partii ular rock was proposed by Landwehr (57). A danger figure was at- 00 tribu .ed to each mineral constituent of the rock and multiplied by the weight CCTdO present. T he products for all the constituents were then summed, and the n total was multiplied by a fraction representing the percentage of fine dust f) generated by drilling. No account was taken of constituents which could O suppiess fibrogenic activity, nor of the fact th a t the " danger" of a mineral might be a result solely of its quartz content; felspar, for example, was rated as 70 per cent as dangerous as quartz. A scheme of this nature suffers from the limitation th a t the effects of quartz are different from those of other rocks, which makes it rather misleading to classify them together. Land Cl wehr s treatise contains useful inform ation about a number of rocks. C The olivines, orthorhombic silicates of magnesium, and ferrous iron ap pear to provoke little fibrosis in the lungs. Experiments on rats by King et al. (58), using intratracheal injection of saline suspensions, revealed phago cytosis with the alveolar walls thickened because of congestion of the lym- p h a t cs by dust containing macrophages. Slight fibrosis was present in the 3 alveclar walls, b u t there was no organized focal nodulation. These minerals are used as a substitute for siliceous sand in various industries and have con tributed to the decline of silicosis. S-incite, a muscovite or potash mica, is an alteration product of felspar. oi Some historical interest attaches to sericite because Jones (59) claimed th a t it was 1he cause of silicosis. His argum ent was based upon his discovery in the lungs of silicotic miners of large numbers of fine needles of sericite under 2 n CL in length; qu artz particles were also present b u t in numbers subordinate to sericite. Evidence against this theory was put forward (60 to 63), and both Lemon & Higgins (64) and King et al. (65) found th a t sericite produced a minimal tissue response when injected into r a ts ' lungs; appreciable fibrosis was evoked if the dust was treated with hydrochloric acid before injection CL though anomalies between solubility and pathological effect were observed. 0 Lancwehr (66) claimed sericite to be harmless on its own but to act as a catalyst and to enhance the danger of quartz; his evidence for this s ta te ment is not clear. S upport for L andw ehr's hypothesis is found in papers by C-1J Weil and (67) and by H urlbut & Beyer (68). T he experiments of the former, on guinea pigs, seem to have been confused by intercurrent disease. The O0)" latter compare two foundries, one with many cases of silicosis and th e other XJ 6 with none. While associating the disease with the sericite content of a p a r t OO ing powder used in the bad foundry, and even commenting on the fact that <OCL the castings which it turned out possessed a finer finish than those from the IT otheq they entirely fail to record any details of the fettling processes or measurements of dust concentrations during this operation, which was obvi Li.) ously prosecuted more vigorously in the foundry with the high incidence of OO TJ5 CQ THE PE disease. T he fettling of It is difficult to credit of quartz within the It An examination of quartz and felspar witl cosis only amongst m< could be ascribed to m mines, b u t this was pre drillings to an extent 1 Sericite and mica fr dusts in pneumoconio inhibitory action can b ence in the slate indust ble to the silica contei and mica. The first wo content is high (35 per carried out by Wade ( where the free quartz workers in slate which being largely sericite, Italian slate also conf 8.6 per cent. X-ray pi slate revealed initial s merit; silicosis and tu The diseases had thus The suggestion tha sis because the particl an exaggerated incide velopment of disease tainly no gross effect quartz dust This su Bruckmann (76) on tl talc platelets in lung be accounted for by 1 quartz and Canada b particles in C anada be microscopy of the hit size must be subject fi M any silicates cr} longer fibres; the latt asbestos, the fibres c tudinally an indefinit Sillimanite an anl ce of diffuse fibrosis, ictors which can be r inert silicates. :o dust made from a inger figure was at:iplied by the weight n summed, and the centage of fine dust ituents which could anger" of a mineral example, was rated . nature suffers from from those of other em together. Landmber of rocks, and ferrous iron apits on rats by King ons, revealed phagongestion of the lym3 was present in the tion. These minerals istries and have con i product of felspar. 3(59) claimed that it his discovery in the of sericite under 2 ju ibers subordinate to (60 to 63), and both . sericite produced a appreciable fibrosis tcid before injection ;fleet were observed, own but to act as a lence for this state3found in papers by ments of the former, :urrent disease. The licosis and the other te content of a partting on the fact that than those from the fettling processes or ion, which was obvi:he high incidence of THE PHYSICS AND CHEMISTRY OF DUST 331 disease. The fettling of castings is the principal cause of silicosis in foundries. It is difficult to credit the theory of Hass (69) that sericite is formed out of quartz within the lungs. An examination of men working with mica and pegmatite (a mixture of quartz and felspar with some mica) by Dreessen et al. (70) revealed true sili cosis only amongst men exposed to quartz, though effects were seen that could be ascribed to mica dust. Silicosis has been reported in the Bihar mica mines, but this was probably a result of free silica which was present in rock : drillings to an extent between 11 and 67 per cent (71). ! Sericite and mica frequently accompany silica in silicotic lungs and other I dusts in pneumoconiotic lungs, and it is improbable that any appreciable inhibitory action can be ascribed to them. This view is supported by experi ence in the slate industry where the danger of the dust is probably attributa ble to the silica content and is not greatly influenced by associated sericite and mica. The first work on exposure to slate dust in Wales, where the silica content is high (35 per cent) and there is a long history of tuberculosis, was carried out by Wade (72). Silicosis was detected in Australian slate quarries | where the free quartz content was 33 per cent (73). In France, however, workers in slate which had a free silica content of only 7 per cent, the rest being largely sericite, showed few signs of respiratory impairment (74). Italian slate also contains a low percentage of quartz, ranging from 2.8 to 8.6 per cent. X-ray photographs of personnel engaged in working Ligurian slate revealed initial signs of pneumoconiosis after 10 to 15 years' employ ment; silicosis and tuberculosis existed only in men who had retired (75). The diseases had thus required a full working lifetime for their development. The suggestion that micaceous minerals are liable to cause pneumoconio- j sis because the particles are flat lamellae does not seem to be borne out by . an exaggerated incidence of disease or by a particularly rapid rate of de ' velopment of disease amongst persons exposed to mica dust. There is cer , tainly no gross effect comparable with the vicious attack from crystalline i quartz dust. This suggestion has, however, been made by Landwehr & ! Bruckmann (76) on the basis of a lack of quartz and an excess of mica and talc platelets in lung sections seen under the microscope. Their result may be accounted for by the small difference between the refractive indices of quartz and Canada balsam which makes the identification of small quartz , particles in Canada balsam mounts a difficult matter. Any estimate by visual microscopy of the lung content of dust in particles of the order of 1 x in ! size must be subject to considerable uncertainty. i F ibrous Crystalline Silicates Many silicates crystallise in fibrous form, both as short spicules and in ' longer fibres; the latter may be either brittle or else silky and flexible, like I asbestos, the fibres of which also possess the property of cleaving longi tudinally an indefinite number of times. Sillimanite, an anhydrous aluminium silicate used for special purposes in 1 332 DAVIES the pottery industry, crystallises in hard acicular crystals which do not cleave but are readily ground to powder. Middleton (77) stated on limited evidence that the dust did not appear to be highly dangerous, but it was later held responsible for lung fibrosis, including nodulation, in men engaged in making artificial corundum by heating bauxite and kaolin in an electrical furnace (78, 79). When rabbits were exposed to airborne sillimanite dust, fibrosis of the lungs with some nodulation was observed (80). Other reports of bauxite fume pneumoconiosis suggest that it is caused by the inhalation of extremely high concentrations of colloidal silica aerosol and that the presence of sillimanite in the fume is incidental. The end result, in these cases, was diffuse, inter stitial fibrosis without nodulation, deriving from interference with the koniophage clearance mechanism by the large quantity of dust present in the lungs and the high solubility of colloidal particles of silica (81 to 84). King et al. (85), however, have produced a dense, collagenous fibrosis in the lungs of rats by administering large quantities of colloidal alumina (A IA ). Sepiolite, or meerschaum, a light hydrated magnesium silicate resembling cuttle-fish bone and containing both fibrous crystals and amorphous material, has been cited in one case as a cause of "silicatosis" (86); the x-ray pictures show diffuse shadowing. The association of the shape of inhaled dust particles with disease is particularly interesting in the case of talc, a hydrated magnesium silicate forming monoclinic crystals which are soft and cleave into small scales and spicules. Dreessen & Dallavalle found that Georgia talc, a hydrous magnesium silicate containing 20 to 30 per cent of dolomite and 10 per cent of tremolite, was more injurious than tremolfte talc (87, 88), though the damage caused was in no way comparable with that attributable to silica dust. The Georgia talc contained many fibrous splinters and aggregates and was composed of hydrous magnesium silicate. Tremolite is a hydrous calcium magnesium silicate which occurs both as slender, blade-like prisms and as silky fibres. Hogue & Mallette (89), after examining rubber workers exposed to pure talc containing neither fibrous varieties nor free silica, decided that this sub stance did not produce pathological changes in the lungs, but emphasized that the term "talc" was used commercially in a wide sense to include tremo lite, pyrophyllite, and even quartz. Massive lung shadowing in miners of pyrophyllite, a hydrated aluminium silicate similar to talc and occurring in foliated, lamellar and somewhat fibrous masses, was observed by Eason et al (90), but the dust contained from 25 to 35 per cent of free quartz. Porro etal. (91) found pneumoconiosis in tremolite workers whose lungs exhibited fibrosis and contained talc bodies resembling asbestos bodies when examined post-mortem. That the fibrous varieties of talc produce a disease analogous asbst0sis>Wlth^ lffuse fibrosis and asbestos bodies, is confirmed by Siegal et al. (92) and by Greenburg (93). THE PI Several other case dust and diagnosed b; without reference to t scribes a generalized f which contained less from the sharp spicule had been 24 years' e which, with the x-raj pneumoconiosis. McLaughlin et al lungs of a worker in carditis. Although th< for 33 years contained to 10 n in length, wer in the root nodes but more numerous in thi characteristic pattern fibrous particles and found in cases of asb Rapid developmei similar to silicosis, in is described by Alivie up to 1,925 particles count for pronounced unless a fair proporti is given on this poin Miller & Sayers ( lowing the intraperit and soapstone (65 p therefore, classed thi borne talc dust wh bronchial reactions a but the animals were enough for it to be re skin and peritoneum Asbestos shares t years, a high degree The disease, asbesto occurrence was held (110). Its associatio sis, though this is i Germany (111). Pei contracting cancer c served with other p Asbestosis differ THE PHYSICS AND CHEMISTRY OF DUST 333 Several other cases of pneumoconiosis, caused by long exposure to talc dust and diagnosed by x-ray as differing from silicosis, have been reported without reference to the shape of the particles (94 to 99). Millman (100) de scribes a generalized pneumoconiosis from exposure to talcum powder dust which contained less than 0.5 per cent of free silica and was entirely free from the sharp spicules found in the fibrous variety of tremolite talc. There had been 24 years' exposure, a long period, to high dust concentrations, which, with the x-ray reproduced, suggest this to be a case of inert dust pneumoconiosis. _ McLaughlin et al. (101) made a very thorough examination of the lungs of a worker in a rubber tyre factory who died of rheumatic endo carditis. Although the Norwegian talc dust to which he had been exposed for 33 years contained both platelet and fibrous particles, only the latter, up to 10 [i in length, were recovered from the lungs. Fibrosis was not observed in the root nodes but was scattered throughout the lung in small nodules, more numerous in the lower lobes, which were less compact and lacked the characteristic pattern of silicotic nodules. These nodules were packed with fibrous particles and contained "curious bodies" somewhat similar to those found in cases of asbestosis. There had be^u no exposure to asbestos. Rapid development of talc pneumoconiosis, clinically and radiologically similar to silicosis, in workers exposed to very heavy concentrations of dust is described by Alivisatos et al. (102). No free silica was present. Dust counts up to 1,925 particles per cc. are quoted; this would not be adequate to ac count for pronounced x-ray shadowing in periods as short as 16 to 60 months unless a fair proportion of long, fibrous particles was present. No information is given on this point. Miller & Sayers (103) obtained only an initial foreign body reaction fol lowing the intraperitoneal injection of talc (75 per cent fibrous tremolite) and soapstone (65 per cent fibrous tremolite) dust into guinea pigs and, therefore, classed them as inert, while Policard (104), exposing rats to air borne talc dust which contained needle-shaped particles, observed only bronchial reactions and loss of mobility of phagocytes. No fibrosis was found, but the animals were killed off after 20 days which may not have been long enough for it to be recognised. In the human subject talc granulomata of the skin and peritoneum have been described (105 to 109). Asbestos shares with quartz the capacity for producing rapidly, in a few years, a high degree of fibrosis of the lungs when inhaled as airborne dust. The disease, asbestosis, was first recognised in 1906, and an inquiry into its occurrence was held by the Factory Department of the Home Office in 1928 (110). Its association with tuberculosis is infrequent, compared with silico sis, though this is less marked in England than in the United States and Germany (111). Persons affected with asbestosis have an increased risk of contracting cancer of the lung (112, 113), a tendency which has not been ob served with other pneumoconioses (114, 115, 116). Asbestosis differs from silicosis in additional ways. It does not progress 334 DAVIES after exposure to the dust has ceased, and it is characterised by diffuse x-ray shadowing as a result of pulmonary fibrosis which, unlike silicosis, chiefly affects the bases of the lungs, spreading to the middle and upper parts as the disease advances, with the apices usually clear. The laminated, fibrous nodules of silicosis do not grow as a result of the presence of asbestos in the lungs; instead, a diffuse, general fibrosis without calcification is stimulated. Characteristic asbestos bodies are found in the fibrous tissue, air spaces, and sputum and within macrophages; they consist of asbestos fibres sheathed with iron-containing protein derived from the capillary exudate. They were first observed in the lungs of an asbestos worker in 1927; similar objects have since been found in cases of talc, graphite, carborundum, and coal pneumoconiosis and, possibly, byssinosis. Asbestos bodies may be up to 250 /r long; ultimately, they appear to break up and disperse (117, 118, 119). Injection of asbestos bodies into the peritoneum of guinea pigs failed to pro voke the fibrous reaction observed with naked fibres (124); Miller & Sayers (103), however, found asbestos fibres to be inert by a similar technique. Asbestos fibres produce granulomata of the skin, or asbestos corns (120, 121, 122), which do not contain asbestos bodies. An immediate inflammatory reaction in the peritoneum of mice has been caused by fibres detached acci dentally from an asbestos sterilizing filter; talc acted similarly, but glass fibres and mica produced only a slight response with no immediate effect from silica (123), possibly because the particles were too coarse (140 mesh) Histologically, the characteristic feature of, asbestosis is the growth of fibrosis around the fine bronchioles and alveolar ducts, suggesting th at as bestos fibres lodge across air channels which are of appropriate diameter and work into the surrounding tissue by virtue of its movement during respiration. This has been supported by the results of many animal experi ments at Saranac by L. U. Gardner which have been reported by Vorwald et al. (124). These showed that peribronchiolar fibrosis could be produced in guinea pigs, cats, and rats by inhalation of asbestos dust containing fibres around 10 ju in length. No effect was produced in mice. Inhalation of dust almost free from long fibres produced little fibrosis. Further experi ments by intratracheal injection of long and short fibre dusts, using various kinds of mineral, were carried out. Using fibres 20 to 50 x long it was shown that chrysotile, amosite, crocidolite, tremolite, and brucite were active; for some reason anthophyllite was not. Brucite is a fibrous form of magnesium hydroxide which is free from silica. Glass wool, of the same length and 3 ja in diameter, produced no fibrosis. When the dusts were ground before ad ministration, so as to break up the long fibres into pieces 3 ju and less in size, no fibrous reaction was produced by any of them; the only effect observed was a greater or lesser inflammatory reaction with transport by phagocytes to the lymphatics. The association is with the fibrous habit of the mineral, not with its crystalline form; chrysotile is probably rhombic, amosite is orthorhombic, crocidolite and tremolite are monoclinic, and brucite belongs to the rhombohedral section of the hexagonal systems. Anthophyllite is orthorhombic. T , THE PI All these minerals, be growth along a partic' of their formation, ma repeated longitudinal and his colleagues cc cleaving fibres of glass j and his co-workers clit 1 venous and intraperite Quartz particles be ; in various organs, sue hyalinised fibrotic no ground to particles si jections of the short fit : excited by inert dusts, \ ing anthophyllite, ga\ 1 It is also claimed spleen did not cause a l and peritoneum are m tissues. Full details of i Further evidence . ! is afforded by their ot inhibit asbestosis, wl aluminium had no ini 1 quartz (126, 127), altl ; Observations on t chanical factor in its < of asbestosis in a mai of particles up to 4,0( | were no localised nodi [ in the lower parts of e isolated and in group lungs, but also in the Cartier, describin; states that all cases duration to concentr chrysotile asbestos fil 250 x long. This coni be required to cause s | of the figure associate ! of exposure. Other c appeared to be harm Asbestosis from F by Noro (131). Fibres the fibres being most! fibres up to 65 fi long Dreessen et al. (1 THE PHYSICS AND CHEMISTRY OF DUST 335 All these minerals, because of an enormously exaggerated rate of crystal growth along a particular axis being encouraged by conditions at the time of their formation, may occu r in the fo rm of lo n g fibres which are capable of repeated longitudinal subdivision. It is this growth habit which yorwald and his colleagues correlate with the power to produce asbestosis, non cleaving fibres of glass of similar length do not cause the disease. Vorwald and his co-workers clinch their argument with observations following intra venous and intraperitoneal injection. _ Quartz particles below 3 ju in size, when injected into the veins, collected in various organs, such as the liver and spleen, and caused the growth of hyalinised fibrotic nodules of characteristic type. The asbestos^ minerals, ground to particles shorter than 3ju, produced no effect. Intraperitoneal in jections of the short fibre dusts caused only the phagocyte reaction commonly excited by inert dusts, with no fibrosis. Long fibre asbestos minerals, includ ing anthophyllite, gave rise to fibrosis. _ It is also claimed that direct injection of long asbestos fibres into the spleen did not cause asbestosis because this organ is static, whereas the lung and peritoneum are mobile, which makes the ends of the fibres work into the tissues. Full details of this experiment are lacking from the paper. ^ Further evidence in favour of mechanical, rather than chemical, action is afforded by their observations that colloidal aluminium hydroxide did not inhibit asbestosis, while King et al. (125) found, similarly, th at metallic aluminium had no inhibitory effect. These substances prevent fibrosis from quartz (126, 127), although an exception has been mentioned by King (128). Observations on the disease in humans confirm the existence of a me chanical factor in its origin. A typical case is described by Luton et al. (129) of asbestosis in a man who died after 18 years' exposure to concentrations of particles up to 4,000 per cc. containing fibres up to 10 n in length. There were no localised nodules in the lungs, but a general thickening of the pleura in the lower parts of each lung was evident. Many asbestos bodies were seen, isolated and in groups, and dust particles could be traced, not only in the lungs, but also in the vessels of the liver, kidney, and spleen. Cartier, describing conditions at the Thetford mines in Canada (130), states that all cases of asbestosis arose from exposures of over 14 years duration to concentrations exceeding 18 particles per cubic centimetre of chrysotile asbestos fibres, which were dry, partially cleaved, and from 10 to 250 n long. This concentration is of the order of one-tenth of what would be required to cause silicosis from quartz dust, and less than one-hundredth of the figure associated with an inert dust pneumoconiosis in the same period of exposure. Other dust, consisting mainly of powdered serpentine rock, appeared to be harmless. _ Asbestosis from Finnish amphibole, a hard, brittle variety, is described by Noro (131). Fibres and asbestos bodies were found in the lungs of victims, the fibres being mostly 9 n or less in length and under 1 n in diameter; a few fibres up to 65 ju long were seen. Dreessen et al. (132), in an exhaustive study of an asbestos textile in- 336 DAVIES ) The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U.S. Cop dustry, where the risk of asbestosis is much greater than in mining, found airborne fibres of a median length ranging from 7 to 163 x. Asbestosis was diagnosed in many workers and asbestos bodies were found in the lungs. Dreessen and his colleagues comment on the very low dust concentrations which could be held responsible for causing the disease. Concentrations below 180 particles per cubic centimetre, measured with a Konimeter, were sug gested as being safe; as no attem pt was made to distinguish between fibrous and nonfibrous particles, this does not necessarily conflict with Cartier's figure given above. The asbestos was mainly chrysotile. Alden and Howell (122) describe corns produced in 99 out of 167 workers with amosite. No asbestosis was detected, but figures for the airborne dust concentration are not included. These facts do not oppose the theory that asbestosis is caused by fibres penetrating the tissue of the primary lung lobule, in the airways of which they are held up on account of their length; it is also conceivable that easy longitudinal cleavage of the fibres, which results in fraying of the broken ends, may be a necessary physical factor additional to a length exceeding 10 n. In spite of the failure of aluminium to inhibit fibrous growth, however, the possibility of a specific chemical reaction at the ends of the fibres cannot be excluded. Asbestos bodies provide visual evidence of chemical action against the invading fibres, probably to render them innocuous, with special activity at fractured ends. The ultimate development of cancer cannot readily be ac cepted as resulting from mechanical stimulus, or the presence of fibrous tis sue, without postulating some accessory cause. The asbestos corn, stimu lated by small slivers penetrating the skin of the hand, under which a fibrous response is initiated, seems to be more specific than a foreign body reaction. The handling of glass wool, slag wool, and even glass fabrics causes skin irri tation because of the pentration of glass fibres, but corns are not produced, nor is there evidence of pneumoconiosis, although long exposures have not yet been recorded (133, 134, 135). Finally, Kettle (25) injected ground as bestos into subcutaneous connective tissue and produced active lesions, like those attributable to silica. ' In considering the reaction of tissue to dust, both the immediate inflam matory reaction, and the long-term, fibrotic effect, have to be differentiated. Regarding the latter, asbestos and talc dusts appear to be selective in respect of both the organ and the species of animal, which is not the case with quartz. Quartz dust provokes a fibrogenic reaction, with only minor dif ferences between species, in every organ capable of retaining particles and in every kind of animal which has been investigated (136, 137). Miller & Sayers (103) found no fibrosis in guinea pigs injected intraperi- toneally with asbestos and talc. Gardner (136) obtained only a very slight effect in the lungs of mice and dogs with asbestos while man, guinea pig, cat, and rat developed fibrosis. He inoculated the dog by intratracheal injection of a suspension of long chrysotile fibres in saline which failed to produce more THE PHYSICS AND CHEMISTRY OF DUST 337 than minute granulomata in peripheral lymphoid tissue, although observa tion was continued for two years. Inhalation was employed for the mouse; asbestos bodies were formed, but the tissue response remained limited to phagocytosis over a period of two years. Yet the dog can experience asbestosis, for Schuster (138) describes one which had inhaled dust for 10 years in a factory where three kinds of asbestos were handled. The lungs contained fibres from 8 to 60 ju long, and there was considerable diffuse, interstitial, peribronchiolar, and perivascular fibrosis. Asbestos bodies were absent. These variations in the response to asbestos fibres are peculiar, and it is doubtful if they are genuinely a result of differences of susceptibility. For fibrous growth to be initiated, contact must be established between the stimulating agent and an area of connective tissue. It is conceivable that this contact is mechanically uncertain in the case of long fibres, especially when they are administered by the injection of a liquid suspension; more uncertain than is the case with granules of quartz. The relationship of the immediate inflammatory reaction, which is often produced by the injection of foreign material into tissue, to the long term fibrosis also requires consideration. Kettle (139) describes a tissue response to subcutaneous injections of colloidal silicic acid which included necrosis and the ultimate development of a fibrous scar. He also produced similar lesions from the solution of silicic acid which leached out of a permeable collodion bag of silica embedded in tissue. It is doubtful if these lesions can be regarded as analogous to the prolif erating silicotic nodule. Gardner, Miller & Sayers, and other more recent ex perimenters, disregard any initial reaction and concentrate on the growing nodule, which is evident only after a period of weeks. Kettle's asbestos lesions referred to above (25) may come into the same category as his silicic acid scars. Complete disregard of the variable initial reaction seems unjustified, at least in the case of asbestos, because it is doubtful if asbestosis in humans is progressive. There may be a similarity between the asbestos scar in the connective tissue under the skin, and the lung condition of asbestosis. P hysical and Chemical F actors in P neumoconiosis The difference between silicosis and asbestosis arises from the physical difference between the two dusts which cause them. Silicotic nodules are focal collections of large numbers of particles which have been gathered to gether from the distributed sites of their original deposition upon the walls of the air spaces in the lungs. The focalisation is a result of phagocyte ac tivity and lymph currents, and it is necessary to postulate th at the silica particles cannot harm the phagocytes appreciably if this description is ac cepted. It is physically impossible for a long fibre, over about 20 i, to be engulfed by a single phagocyte; hence the building up of focal aggregations of such 338 DAVIES Prtfcie, cannot take p i* ., and the fibrosis which they prodnce must be dlf i broMhidewntTalveoHsbice t"ey0im!)i *TM " * admiltri * lh' "' the ciliated wall, of the bronchi and bronchioles^ ,,'e"cZ S `f Z fib" they move relative the is abn U 1^ y V ^ " ^ M i ^ tt i P a strong tendency to travel with an air stream, which e x l ^ t t ' m lung tissue of asbestos fibres up to 250 Mlong occurrence sihcost * T 2 e a . e br , h t r m Df na,, ? t " " ' ^ 0 TM '" a " h e r f h e r ^ r n t t ? s: m - ; 1^ ^ S T b " L T ; r ; r 1,is,h^ nodIsh: i" t a i . i d e l m a l T l ,, dr , . T "1,,bin 7 ' 'bmph reaction has been observed from th e s e T h e T n e g f Cyt0Sed' Mlkl fibrous primary lobules and produce local fibrosis Tt, 8 fib.res,are cau8ht ln the by McLaughlin et a l (101) seems to hP i V ^ ^ [ ta Cfibrosis reported focalisation found with quartz dust and th ermedjate between the complete sis, attributable to fib L exceed t e 20 . " " ? ? diffuSeness of " b o - ;S r r ;LbPZTLTii*TirlenEth number of nodcte " ): ," , ' `ma ' P "(Ion, and large bbre length I n c ^ L T b . ^ , , " " 8r W' " S > * TM P the tu b S :TM TM " ~ ; r vi i " r - c f a ,,.am .. and fluid and fibre-forming J k n l n ? i , ' h" 4 `"tercellular material i make fibre, i, yet d , J T l ' "" chan,,m by which the cell, taining an acidic p o I y s Z c ^ W e C L " " " a"d <142>' precipitate the fibres extracellularly by a proc^coM ron i T ' " "*a" '1 may Z 7'Z ^ 7 ` and electrostatic interaction, w iti n d g h Z d n g m i t , ^ T l l " 0 A i e ' S " , " r ^ p e T e t, relate, with the unspecific M u r , of , ` "* which growth mechanism com mon^an6speciesenmenta !ili" ' iS " d a can stimulate tlw 'fil,!)TM )^, - resulting ,,odn.es fro C P*rlides in connective tissue THE PHYSICS AND CHEMISTRY OF DUST 339 must be some feature in the chain of causation common to the crystal of quartz and the tubercle bacillus. The association of tuberculosis with dusty occupations was observed before the identification of silicosis and the ex perimental increase of the local reaction to tubercle bacilli in the Pre; ^ c e of colloidal solution of silica, itself toxic (145), is well established (146, 147). Gye & Purdy (145) showed that the tissue change induced by silica sol ad ministered parenterally consisted of a slow thickening of capillary boundaries by a deposit of collagen, and their work encouraged the theory that solution of silicic acid from quartz particles in the lymph tissue initiated fibrous growth. It could equally well be argued that silica would be precipitated from the colloidal solution owing to its particles aggregating at the low pH of blood and, depositing in the connective tissue irrigated by the capillaries, would initiate collagenous growth near their walls. This view persisted for 30 years in spite of certain difficulties. Banting (148) was one of the first to distinguish clearly the peculiar nature of the growing silicotic nodule as distinct from the local toxic action, necrosis, and formation of scar tissue which followed the injection of colloidal silica, sol. He showed that nodules could be produced only by particulate silica; in addi tion he repeated Kettle's experiment of implanting a permeable bag of silica into tissue and failed to obtain nodules. Banting's conclusion was that par ticulate silica caused silicosis and th at fibrosis might be initiated by t e phagocyte changing from an amoeboid to a connective tissue ce . The solubility theory persisted, nevertheless, with support from the o served decrease in silica solubility caused by the presence of small amounts of iron (25) or aluminium and of larger quantities of calcium hydroxide or cement (126, 127), or by the presence of other rock dusts (128). ^ _ There was some evidence of a parallel diminution of fibrogenic action, though exceptions were noted. Reports of siliceous dusts which were failing to produce silicosis were accounted for by the assumption of a depression, by another constituent, of silica solubility, as mentioned previously, and were accepted as evidence in favour of the solubility theory. It was also found that the fibrogenic effects of certain silicates ran parallel with their solubilities (154); the weakness in this argument lies in the in direct and unspecific association between the dust administered and the re sulting fibrous growth, except in the case of free silica. _ The grounds for believing that silicic acid, dissolved from particles of silica and silicate by the lung fluids, is the agent which stimulates abnormal collagen production in connective tissue are extremely tenuous. There is no positive evidence apart from the experiments of Kettle (25, 139) by sub cutaneous injection of colloidal silicic acid, which must be regarded as doubtful because of the nature of his lesions; these were not growing nodules but contained areas of scar tissue repairing regions of necrosis produced by the toxic action of colloidal silicic acid; crystalline silica had a much smaller effect. Necrosis in the silicotic nodule does not precede fibrosis but is sub sequent to it. DAVIES An apparent abundance of iamined critically. On 'le o n e an mconiosi. With absence of nodnlarion d.m e * of simple P" *- shadowing or reticula- y to .ilkeous ion without discrete op,a,., " d usts. These are cited a . m .tance. of `he " ,,i ,,lability. I t is imand analyses of the ,erative th at accurate measureme mea, be made in such cases. each group. . . pntal work with animals. Evidence of On the other hand is the p ^ ^ ^ upon silica particles seems to the preventive action of Kettle (25) using the method of subcu- ^ h l M h i s m S . beTM S " f " " di" ,Ved ` W ' he dust particles had deposited in * dust (150) is usually quoted as The work of Gardner on carborundum dust mechanical trauma supporting the solubility theory agai himself maintained; his by hard, sharp particles, a conclusion th e ^ a u th o r ^ ^ ^ ^ paper describing the effec s o . the lungs 0f the control animals, which had'inhaled^dust, in comparison w i t ^ ^ - : f s X % 1 X t t ^ ; t r o s r . f T i g parenchyma' j ft. hVip dust controls and the injected The tracheobronchial lymph>nodes in hat later date than did the cor series showed microscopic dust deposits at^ was found> but it was responding granite series, at m considerable quantity of dust had collecte . not until the fourth month that " V was a steady inCrease in the deposits From then on, until the sixteenth in both series. In the last five animal > iarge quantities were contained in all J ^ period there was a very definite parts of the nodes. In the two dus \ obliterated the medullary sinuses. This ^ o - n c e n t r a t i o n of excessive amounts of irritant within a small focus. Gardner ,, so comment.r on tb . a.tera.ion * S 3 S `p t i l i y t l f n ^ y resolution, to a progressive tnberenfar brB oth the encouragement of t u b e r c u l o s ^ a ^ a t tri- as the result of the presence of an inert dus . THE PHYSICS AND CHEMISTRY OF DUST 341 The difficulty of carrying out inhalation experiments led to the use of intravenous and intratracheal injection. Gardner & Cummings (151), using the former technique, showed the importance of particle size. Particles of quartz between 6 and 12/* in size failed to produce silicotic nodules, while particles between 1 and 3ju did. The particles were transported by the blood stream to lungs, liver, and spleen; no reaction was observed in the kidneys. Necrosis and scar formation resembling that described by Kettle was pro duced at the site of injection in the ear. The idea that a dust with a high specific surface was especially dangerous on account of its enhanced solubility was thus encouraged, but later experi ments showed the existence of an optimum particle size for fibrosis in the region of 1 to 2ju (152, 153). _ The great objection to the solubility theory of silicosis came with the discovery that the solubilities of various forms of silica did not always run parallel with their pathological effects (149, 154, 155). In the first place, it was established that samples of quartz from which an initial quantity of silicic acid could be leached readily did not thereby lose their fibrogenic effect, even though their subsequent solubility was very low. Secondly, four forms of silica, i.e., vitreous silica, quartz, cristobolite, and tridymite, have similar solubilities but produce differing fibrogenic effects, the intensities broadly increasing in the order named (156, 157). The experiments of Kettle were conducted with colloidal solutions of silicic acid, and it is only recently that the physical chemistry of solutions of silica has been worked out sufficiently for their significance in the solubil ity theory of silicosis to be appreciated. Solutions of silicic acid may contain both monomeric and dimeric molecules and polymerised aggregates of sizes ranging up to the colloidal particles present in Kettle s solutions. Molecularly dispersed solutions are excreted to a large extent after oral or intravenous administration without damage to the animal (158), and after oral administration of silica and silicates in man (159). Colloidal solutions, however, are toxic (158), precipitate protein (160), and produce scar type fibrosis, though not in the lung, from which they are too rapidly drained away (160). Policard & Collet (161) claim that the fibrosis is qualitatively similar to that produced by crystalline quartz, but quantitatively more prolific. There has thus been a tendency to accept the innocuous nature of molecular silicic acid and to associate the growth of silicotic nodules with colloidal solution. _ The immediate objection to this view is that nothing remotely resembling a nodule has ever been produced by the administration of colloidal silica to animals, while human beings exposed to the dust of amorphous (not vitreous, which acts like crystalline) silica rarely develop disease unless the concen trations are abnormally high; in this case the clinical picture is quite dif ferent from silicosis (81 to 84). These points are countered by arguing that inhaled dust of amorphous (i.e., dry, colloidal) silica is so soluble that its action in lung tissue is pro- 342 DAVIES foundly modified, whereas classical silicosis could be attributable to the production of colloidal silicic acid in situ from particles of silica. Doubt is thrown upon the last hypothesis by the failure to find amor phous silica in lung residues and by the fact that it is impossible to demon strate the presence of colloidal silicic acid in extracts from crystalline or vitreous silica prepared under conditions which could hold in the lungs. At high pressures and temperatures colloidal solutions are formed di rectly but the quantity of silica dissolved has fallen to .02 per cent when the temperature is down to 200C. (162). At body temperature solutions con taining less than .016 per cent S i0 2do not form a colloid; the transition from a true solution to a gel is slow in the vicinity of the above concentrations, and it is extremely unlikely that so high a figure is ever attained in tissue fluids (163). . .... Baumann (164) emphasised the complicated nature of solution eqm l - rium between crystal, colloid, and molecular phase, and the time taken to become stable; as a result, many determinations of alleged solubility were i reality measurements of rate of solution. ^ . His figure for the solubility limit of molecular silicic acid was -012 to 014 per cent over the pH range 4.5 to 9.0, with a much higher value in more alkaline media. This figure was obtained for equilibrium between amorphous silica and solution, and it is interesting to note its closeness to the figures above for crystals at 200C. (162) and gelling solutions prepared from sodium silicate (163). . f Paterson & Wheatley (165) found the equilibrium concentration of molecular silicic acid to be .014 per cent irrespective of the presence of colloidal silica solution, but could not obtain any colloid in solutions made with crystalline silica. A suggestive feature of these investigations is the recurrence of a figu e around .014 per cent for equilibrium with both crystalline and colloi material. It is certainly possible that the crystal surface is contaminated locally or generally with colloidal particles which are attached U>o^strongly to float away into the solution yet provide a reservoir for maintaining the molecular equilibrium concentration. . As far as silicosis is concerned, the conclusion must be that any col oida silica would have to be associated with the crystalline particles so dose y as to necessitate their virtual contact with the fibre-forming cell in order to stimulate it. The actual amount of colloid could be extremely sm al. Summary Pneumoconiosis is the term used for a group of lung diseases caused by the accumulation of dust in the lungs without systemic effects immediately attributable to the dust. Some dusts are inert and produce neither an obvious reaction in the organ nor symptoms for diagnosis until a considerable quantity of dust has been collected. Free silica, usually in the form of quartz, THE F causes silicosis in whi< focal nodules which c There are many caused silicosis; this is action of quartz by o crease the solubility o conclusive because tl victim of a sufficient reach the lung alveol cause the classical sy in experimental silic other hand, there is is modified by the pr The production < dusts of crystalline urally occurring, the tuberculous infectio mentally by these d less focal. The expe'i to produce such a r< continued inhalatiot development of tu There are thus crystalline or vitrei nodules in connect! developing collageni The pathology of i nature of the fibres of the primary lobu the ensuing fibrosis Colloidal silicic acid silicosis, but the effi attributable to qua solution of quartz THE PHYSICS AND CHEMISTRY OF DUST 343 causes silicosis in which a continuous formation of collagen is stimulated in focal nodules which contain dust. There are many reports of dusts containing quartz which have not caused silicosis; this is commonly put down to the inhibition of the fibrogemc action of quartz by other constituents of the dust which are known to de crease the solubility of quartz. Such reports, however, cannot be regarded as conclusive because there is seldom proof either of the inhalation by the victim of a sufficient concentration of quartz in particles fine enough to reach the lung alveoli, or of the presence of enough quartz in the lungs to cause the classical symptoms of silicosis. There is also a lack of parallelism in experimental silicosis between fibrogenic effect and solubility. On the other hand, there is some indication that the action of quartz in the lung is modified by the presence of a sufficient quantity of an inert diluent The production of developing fibrous growth in the lungs by inha e dusts of crystalline or amorphous silicates is extremely doubtful. As nat urally occurring, these dusts often contain free silica, and the presence o tuberculous infection may simulate silicosis. Fibrosis produced experi mentally by these dusts is usually less than that produced by quartz and less focal. The experimental techniques are drastic and might be expected to produce such a reaction more readily than would be the case with long continued inhalation. Even inert dusts are suspected of encouraging the development of tuberculosis. There are thus grounds for thinking that quartz and other forms ot crystalline or vitreous silica are unique in causing proliferating fibrous nodules in connective tissue. The only other dusts which cause rapidly developing collagenous growth are fibrous silicates, loosely termed asbestos. The pathology of asbestosis contrasts with silicosis because the physical nature of the fibres renders them liable to become caught in the fine airways of the primary lobule. It is possible that chemical factors are concerned in the ensuing fibrosis which seems to lack the active progression of silicosis Colloidal silicic acid is a tissue poison and has been suspected as the cause of silicosis, but the effects it produces lack characteristic features of the disease attributable to quartz dust, and it is doubtful if it can be formed by the solution of quartz in the lungs. ! CD 3CD CD o3 -0o3 CO CD (f) Oo -o 344 DAVIES LITERATURE CITED 1. Ministry of Pensions and National Insurance, Aim. Refit. (1953) 2. Hugh-Jones, P,, and Fletcher, C. M., Med. Research Council Memo. No. 25. (Her Majesty's Stationery Office, London, England, 1951) 4. Fletcherfc^U.^Ber.'med.-wiss. Arbeitstagung Silikose, 119-150 (October, 1951) 5 Fletcher, C. M., Arch. Ind. Health, 11, 29-41 (1955) 6. Cochrane, A. L,, Brit. J. Tuberc., 48, 274-85 (1954) 7. Meister, P., Arch. Gewerbepathol. Gewerbehyg., 14, 214-26-(1956) 8. McLaughlin, A. I. G., Grout, J. L,, Barne, H. J., and Harding, H. 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