Document jBVB86ebqGNMB56dNNZE6meKk

non ' ' C1I ALTER 12 ASBESTOSIS PLAINTIFF'S exhibit SA-S54 Asbestos lias been used for at least 2,01)0 years. Pliny415 A.O. 23-79 in bis Notu'ralis historin described its properties and spoke of the uses of asbestos fabric. "A linen has now been invented that is incom bustible. It is called ` live' linen and I have seen napkins made of it and burnt more brilliantly clean by the fire than they could be by being washed in water. The linen is used for making shrouds for royalty which keep the ashes of the corpse separate from the rest of the pyre. The plant grows in the deserts and sunscorchcd regions of India where no rain falls, the haunts of deadly snakes, and it is habituated to living in burning heat." Hut the material was rare: "When .any of it is found it rivals the prices of exceptionally fine pearls. The Greek name for it is asbesfitwn . . . this kind of linen holds the highest rank in the whole of the world." Asbestos is mined by blasting and quarrying, between 2 and 10 per cent of the mined rock is fibre. The crude asbestos of com merce contains 5-20 per cent of rock, dust and fine fibre which is removed in opening and spinning. The long-fibre yarn (ehrysotiic fibre-length j-inch or more, atnositc up to 6 inches) is used for textiles, packing gaskets, felted paper and for goods made from asbestos cement where maximum strength is desirable. Asbestos of medium fibre-length goes into paper and board, filter pads, brake blocks, brake linings and asbestos cement. The short-fibre (fibre length about ^ to ^ inch) material is useful only for paint, plaster and asbestos cement. Asbestos is used extensively as a mineral filler in plastics. The dangerous nature of asbestos dust was recognized only recently. In this country the first ease of asbestosis to be described was that of a man who died in Charing Cross Hospital in 1900; the second ease was reported 25 years later.416 Jly 1928 there were still no more than ten eases on record.417 The recognition that a pneumoconiosis was caused by the inhalation of asbestos dust followed a few years later, after several other eases had been described in England418 and a heavy incidence had been observed in some German factories.419-420 About this time Hunter421 saw 30 eases of asbestosis at the London Hospital in 5 years. Wyers422 has shown i composition or asiu-stos nn.sr 1-13 that a sharp decline in the incidence ol asbestosis has occurred since the adoption of proper methods of dust control in the factories, and the character of the tliscase has altered; it is now manifested in a more chronic form. Composition of asbestos dust - Chrysotile, 3MgO.2RiOg.2Il zO, is the main asbestos of commerce but crocidolitc and amosite arc also used. 'The native fibrous asbestos is embedded in other non-fibrous or micro-fibrous minerals such as serpentine and talc. Another fibrous mineral, the nun-siliceous Pin- 12.1. Electron micrograph of a dust sample taken by a Thermal Precipitator from the air of an asbestos works. AMu'Moa fibres are present hut there arc also many particles of oilier minerals and amorphous particles. Micrograph by Safety in Mtnet Unearth Enahlwhmttit; f Vnm I 'opyright hrucitc, MgO.HgO, sometimes occurs with the asbestos, brucite is of no value as a textile fibre because its fibres arc insufficiently " flexible. The manufacturing processes entail the breaking-up of massive asbestos into fibres. In this process the non-fibrous material is shattered to give a fine dust having an average particle size much smaller than that of the asbestos fibres. The non-fibrous dust, consequently, settles more slowly than the asbestos and the atmosphere of an asbestos mill with modern ventilating equipment contains far 144 A.MII S KIMS more non-lihrous than fibrous particles. Must samples of air borne dust collected from industrial atmospheres show few asbestos fibres in the size range which is thought to be of pathological import. In the electron micrograph of a sample taken from the air of an asbestos mill by a thermal precipitator, shown in Fig. 12.1, fibrous asbestos particles, non-fibrous mineral particles and the amorphous sooty particles found in the atmosphere of any industrial town can be distinguished. I Inrlhnl and Williams gave the following analyses for dust collected from the rafters of the different departments of an asbestos textile mill: '' Dust I'rnilttrnl in llic hlnnujneture of Asbestos Textiles Talc . CatbonaKMaanetiie Scrpcnlinc Asbestos Others . . . . . . . Picpaintintt Per cent 6 30 2H 14 15 7 OirilinK Per cent 9 27 21 29 K (< Spinning Per cent 5 21 27 27 H 12 Pathology of asbestosis Asbcstosis is a chronic disease. The lesions take some years to develop. In some circumstances silicosis may develop extremely rapidly and death may occur within two or three years of the first cxposuie, but such rapid development never occurs with asbcstosis. Superficially the lungs of a person who has died from asbestosis resemble the lungs of a victim of silicosis. They are hard and incompressible ami they adhere to the pleura. X-ray pictures of the chest of an ashcstotic patient show the lung fields to be interspersed with very fine, shadowy, round spots. They are mostly undefined but occasionally are sharp and they are denser in the middle and lower regions of the lung. The shadows on the X-ray films correspond to regions in which abnormal connective tissue growtli has occurred. This growth of diffuse connective tissue is greater in the lower part of the lung.423 The fibrosis due to asbestos is much more diffuse than that due to silica.421 Whilst in silicosis there arc numerous almost isolated foci, in asbcstosis there is a fine network throughout the lungs. Hunter describes the radiographs as having the appearance of ground glass. The degree of shadowing present in advanced asbestosis ATI [< >!.(>< ;Y ()l; ASIII SInSI.S 145 would have little .significance if seen in silicosis.4-'1 However, Wyers422 slates that the more chronic form of the disease shows up in radiographs as shadows which arc coarser ami more granular in appearance. The most obvious symptoms shown by a patient arc those of dyspnoea. Tuberculosis may lie present but asbestosis is not accompanied by a predisposition to tuberculosis, as is silicosis.121' Quite often there arc no tubercle bacilli in the lungs. Asbestos fibres have occasionally been found in the urine of patients with asbcstosis.42n Half the group of workers with asbcstosis which Wyers422 studied had clubbed fingers. According to Knox and Beattie427- 428 who examined lungs from 25 deceased persons who had been exposed to asbestos dust, the severity of ashcstotic lesions is related to the time elapsing between the first exposure to the dust and death rather than to the mineral content of the lungs. A visual examination of a sectioned diseased lung reveals tissue which is interspersed with sharply outlined, air-free, grcyish-black areas. When examined microscopically, the lung sections are seen to contain many asbestos fibres which lie in the alveoli ami air ducts and in the lymphatics and connective tissue. There are few fibres in the bronchial lymph glands. An asbestos fibre may penetrate the walls of one alveolus into a neighbouring alveolus. The most important position of protective tissue response in the ease of asbestos fibres is the terminal portion of the respiratory bronchiole whereas with minute silica particles it is the peribronchial and peri vascular lymph nodes.318 Lmphysema is always observed in sections from the lungs of a person who has died with asbcstosis. Strobe428 found hardly any phagocytes connected to fibres in the alveoli but there was considerable phagocytosis of the disintegration products of the fibres. Gloyne43'1, however, frequently observed the ingestion of fibres and bodies by macrophages and regarded this as a normal method for the removal of fibres from the lung. Sundius and Bygdcn431 could find only hornblende in the lungs of persons who had died from asbcstosis although the persons had handled materials which contained mostly serpentine. A recent paper on the pathology of asbcstosis is that of Lynch.824 Asbestosis bodies The characteristic feature of the lung sections from an asbestosis case is the presence of large mini hers of peculiarly shaped structures. There may be 8,000 of these asbestosis bodies visible in a section of lung tissue 1 cm.2 in area. Asbcstosis bodies form rapidly in the lungs. They have been 10--i'. 146 ASHFSTO.SIS found in the lungs of a patient, exposed to the dust for only 2 mouths and they may appear in the sputum within 5 months of exposure. Asheslosis bodies in the sputum or in the lung do not necessarily indicate a condition of pulmonary asheslosis. Indeed it has been observed43 that most workers in asbestos factories have asheslosis bodies in the sputum. Asheslosis bodies were found in tiie lungs of one man who had lived near to an asbestos factory lor many years but bad never been inside it! Asheslosis bodies are often seen in the lungs in clumps.433 These formations may occur within the lung alveoli or they may be embedded in lihrous tissue. Stewart, Tattersall and ' i laddow433 state that the clumps in the alveoli are almost certainly derived from clumps in the (ihrolic areas since the alveoli which contain clumps are always adjacent to areas of advanced fibrosis. Clumps of nsbestosis bodies have also been found in the sputum of patients suffering from asbestosis.433'434-435 These formations in the sputum indicate that the lung tissue is disintegrating and they point definitely to a con dition of asbestosis. Originally, there was considerable controversy about the nature of asbestosis bodies. Some investigators believed that they wore "essentially derived from, or associated with asbestos and were, in fact, portions of asbestos fibres in the process of alteration and absorption by hydrolysis, either by direct chemical action or by enzymes".430 Others, such as Cooke,417 believed that their " results completely negatived the theory that the bodies are asbestos or derivatives of asbestos", (,'ookc stated that "if organisms-- staphylococci, for example are incubated with a colloidal solution of asbestos they become silicated and resemble asbestosis bodies". 1 le sought to prove that most of the bodies were actually " vegetable" in origin. A report on the discussion which followed a paper ilescribing an early case of asbestosis437 said: "A second interesting feature . . . was the presence of a body which some thought was an aspergillus. The authors of the. papers held the view that it was a hyphomycctc analogous to that found by Dr. II. 11. Scott in batrachians, or that it belonged to the tuberculariaceae, a family of hyphomycetcs described by Khrcnberg in 1818." An outstanding investigation of the structure, formation, disinte gration and chemistry of asbestosis bodies was made by Jlegcr.438 A lecturer in geology in the Tcchnischcn llochschulc of Hanover, Ifeger was asked to identify asbestos in the lungs of a foreman who had died from asbestosis. Ileger had no knowledge of medicine, anil stated: "I deferred all study of the literature on asbestosis and asbestos bodies, until such time as l should have completed my experimental investigations." In the lung sections which he asju.siosis itonii-s 147 examined, Ileger found asbestos fibres anil asbestosis bodies. There were far more bodies than unchanged fibres. The fibres (Tig. 12.2) were straight, rigid, and extremely thin. Ileger measuiedthe length and thickness of the fibres in one field and gave the following values: 1.1-nuth (|i) 109 94 87 on 49 40 .1,8 10 15 11 2.825 25 Thickness (p) 0-8 tM 1)1 0-1 0 8 10 0 2 0-7 0 1 0 5 0 1 0 1 0 2 Kiu. 12.2. An asbestos fibre in a section oT a hmu (lower half of photograph). A ilisinteuratinu asbestosis hotly is in the upper part of the photograph (X 1,200). f 12.2 to 12.0 arc reproduced from Heger, Virchow's shrhiv., 290, 282, 1933.) . ............ .................. v.iv- . SUIIIC- timcs long fibres were thin or short fibres thick. Very long needles, say 120 p, were seldom seen, hot long needles arc easily broken in sectioning. Uy measuring the optical properties of the fibres (refractive indices, double diffraction, distribution ol the optical vectors, etc.) aod by considering other physical and chemical pro perties, the fibres were identified as ehrysotile. Jlegcr described asbestosis bodies (Idg. 12.3) as golden yellow structures sometimes having the shape of a dumb-bell but more often in the form of a string of irregularly shaped discs, the "string of heads" lorm. At the ends are eluh-likc protuberances. An average diameter of the head is given as 7-7 p and of the shall 3-5 p. 'I'll- length is from 10 to 100 times the thickness. ~ Running down the centre of the asbestosis body, a fibre or a modified fibre may sometimes he seen. Usually the fibre is still 148 ASUI-STOStK straight but it has reduced rigidity and is less brittle. Occasionally the fibre is curved or even coiled. The coating of the fibre is a gel-like substance. Klcctron micrographs41"1 of asbestosis bodies collected from the sputum also reveal a central asbestos fibre which is coated with a gel. When the gel is removed by mieromanipulation, the fibre appears to have transparent edges suggesting that a constituent of the fibre has dissolved. No fibres shorter than 10 p were found, suggesting that short fibres dissolve completely. AMti'KTosiK mums 140 Formation and disintegration of asbestosis bodies Heger suggests that the bodies are formed hv the deposition of protein from the tissue fluid on the asbestos needles until the fibres become completely enshcathcd. lie succeeded in burning struc tures which were similar in appearance to asbestosis bodies by coagulating egg albumin on acid-washed asbestos fibres. The gel generally takes the form of bends because of surface tension effects. If they come into contact with one another, the beads can coalesce. The commencement of the disintegration of the asbestos fibre in the asbestosis body is shown initially by cleavage lines in the cylindrical Imr. 12.3. Asbestosis bodies ( x 800). Chemical composition of asbestosis bodies Microchemical tests on the bodies show that the gel coating is a protein and that the granules therein arc ferric compounds. The Rod is not removed by hypochlorite and this reagent has been used440 to separate asbestosis bodies front lung tissue. Sundius and llygdcn431 gave the following analysis of an asbestosis body: Organic matter . 31% (S, 0-43%) Iron oxide . . 40% I'lOf. <''!% Water . . . 16% "Asbestos" needle . 4'6% An elementary analysis established that the organic matter was mainly protein. Koppenhoffer,441 however, thought that the sheath was not composed of protein. Iur. 12.4. The first stsiRC in the disintegration of an asbestosis body is shown by cle-avaRc lines in the cylindrical portion of the sheath ( x 1,270). portion of the sheath at right angles to the length of the fibre. The heads then show cleavage. Finally the asbestosis body disintegrates completely; afterwards nothing remains but a series of granules from which the shape of the original body can lie surmised. These stages are illustrated in Mgs. 12.4, 12.5, I2.b. The breakdown of asbestos fibres by the formation ami disinte gration of asbestosis bodies in the lung is emphasized by differential counts of fibres made on the lungs of 27 deceased persons who bad been employed in the asbestos industry.428 The figures shown in 150 ASIIl-STOSIS 1 ;iblc J2.I idelicate that, when the time interval between the last exposure to the Oust and death was more than 8 years, there were usually no fibres in the limn longer than 25 p. Fibres in this size range were abundant in the lungs of persons who survived for a Asiti'siosis liomi-s 151 shorter time after the last exposure to the dust. (iinvne,4* also believed that there were fewer and smaller fibres and ashestnsis bodies in the lungs of long-standing eases of ashestosis than in the lungs of workers exposed to the dust for a shorter time. Taiii.s 12.1 ' Particle-size Distributions Dxfircsseti us Pen cutouts of ('mint hi the lft-25-n miitfc exposure viva) C'sise time. time, Nn. Sex Yr. Yr. 3M 23 M 2(t M 9M 17 M 25 M 12 F 2M 5M 21 F 4F 19 F 6M to M 14 M 22 M 1M 27 M 20 M 8F 13 M 7F 28 M II M 24 M 15 M to M 2ft 28 20 II 12 8 32 27 28 33 14 8 22 9 27 7 23 21 25 27 27 ft 2 22 19 14 10 0 0 0 0 0 0 1 2 2 2 2 3 3 4 6 7 8 8 8 8 9 It 14 14 17 21 A ill 1 tOMR, -- + 1 .ess than 5| 4- 4+ + -- 4-- -- 4- 4* 4+ -- + 4* + -- 4" -- ++ + 4* 4- 4* +++ 4- 4* 4" 4+ -- 4-4-4+++ -- 4- 3ft4 458 510 ftl 2 394 ft27 501 ft89 433 573 (>27 522 421 510 517 48ft 010 78ft 829 898 49ft ftl 1 587 720 1,00ft 529 047 Mean psiiticlr nls Os 5 15 |/ 10 25 |i 2ft 35 |; 3ft 45 (/ 45 193 loo 217 100 290 100 389 100 281 too 329 too 257 loo 387 loo 225 100 381 100 29ft loo 359 loo 325 100 322 100 281 100 3ft9 loo 487 loo 521 loo 044 100 59) 100 321 100 418 100 292 100 599 too 707 100 380 100 411 100 3ft 42 51 (.2 79 38 18 33 50 If (>2 41 51 50 4(i 31 0 22 11 4 0 0 0 0 0 2 9 21 0 00 15 < 18 11 92 17 21 0 17 00 17 H 2 ft 20 5 87 25 17 20 0 IK 2 12 0 00 2 \) 4o || 0 t) 20 00 00 00 0 (j 00 (From Knox, J. F., and Ilenttie, J., Arch. nniustr. Uvg., io, 30. 1954.) The formation of asbestosis bodies has been described as a defence mechanism of the body for the detoxication of asbestos fibres.440-443 The bodies appear to he innocuous. Asbestosis bodies were recovered from a human lung, then they were injected intralrachcally into guinea-pigs' lungs. No fibrosis was produced although the bodies remained in the lungs for a year or more. It was possible to produce fibrosis, however, by injecting asbestos fibres. 152 aphi:.stosis Experimental asbestosis Asbestos dust hns been administered to animals by inhalation and by intratracheal, intravenous, intrapcritoncal and subcutaneous injection. The maintenance of an atmosphere containing a suitable concentration of asbestos dust is not easy. 'Tire inhalation chamber used in the Saranac laboratory was a cubical room, length of side 8 ft., in which asbestos dust was thrown into the air by a paddle slowly rotating in a hopper. Since the fibres tend to form trails in the hopper, wire brushes were attached both to the paddle blades and to the floor of the hopper. Animals were kept in this room for periods of 2 to 5 years. Stewart444 caused guinea-pigs to inhale asbestos dust. After 12 weeks, he found numerous asbestosis bodies in the alveoli and some in the alveolar walls. Some of the bodies were "beaded", in the process of degeneration, and they all gave an intense Prussian blue reaction, showing the presence of iron in the outer coating. Scattered, giant phagocytes in the. alveoli contained asbestosis bodies. No fibrosis in the lungs or thickening of the alveolar walls was observed ; the experiments lasted 20 weeks. Large-scale animal studies were made during some 25 years in Gardner's laboratory at Saranac Lake. Vorwald, Durkan and Pratt440 reviewed and summarized this work. When injected intravenously into rabbits, finely ground asbestos (chrysotile, amositc, crocidolite, anthophyllitc and tremolite) produced only the reaction of an inert foreign body. There was no fibrosis of the liver, spleen or other organs as is observed when quartz is injected intra venously. When chrysotile (0-25 g. or less) was injected intravenously 5 of 6 animals died; no reason for the deaths could be found. Guinea-pigs inhaled asbestos for periods up to 33 months. The dust collected about the respiratory bronchioles, where fibrosis developed; the peripheral alveoli were not involved. A segregation of the fibrous and non-fibrous particles was observed, only the latter being transported to the lymph nodes. Asbestosis bodies were formed in 2 months. A cellular reaction was first observed about one year after the first exposure to the dust and a delicate fibrosis appeared after a further 4 months. The fibrosis progressed thereafter and, as the collagen fibres contracted, alveoli were partially closed and distorted. I he appearance of the tissue resembled that of an adenoma; similar structures have been described in the lungs of guinea-pigs which had inhaled silicon carbide.445 When administered to guinea-pigs by intratracheal injection, chrysotile produced fibrosis. Two months after the dust was administered, there was well-marked cellular proliferation and focal ItXI'KHIMl-N'I'Ai. ASIIi-stosis 153 fibrosis about the respiratory bronchioles; asbestosis bodies were not observed. After six months, asbestosis bodies were abundant in the lungs but, perhaps due to the contraction of the fibrous tissue, the reaction was less extensive. Later, the fibrous tissue, still localized around the terminal bronchioles, became hyal'mized until, after 12 months, there were well-developed peribronchial and intrabronchial adenomatoid areas of fibrosis. Species differences.--Although Vorwald and his associates440 obtained a definite fibrotic response to inhaled asbestos fibres in guinea-pigs, no fibrosis could be produced in rabbits. As there were no fibres or asbestosis bodies in the lungs at autopsy, it was argued that the upper respiratory tract in these animals is an efficient filtration mechanism, adequate to exclude fibres from the lung. Well-marked peribronchiolar fibrosis has been observed in rats following the inhalation of long fibre asbestos dust but hardly any asbestosis bodies were present; in mice numerous asbestosis bodies were observed but no fibrosis. Some cellular connective tissue forms a sheath around bronchioles in the lungs of cats following the inhalation of asbestos fibres, but typical asbestosis bodies are not produced. The location of the lesions is similar to that found in guinea-pigs but the lesions develop much more slowly. Fibre length.-- Vorwald and his associates440 compared the fibrogenie activity of asbestos dust of short fibre length (3 p.) with that of samples containing much longer fibres (20 50 p.). The dust was administered to guinea-pigs both by inhalation and by intratracheal injection. Guinea-pigs kept in an atmosphere containing long chrysotile fibres developed lesions consisting of cellular connective tissue about the terminal bronchioles after <S months. The adjacent parenchyma was affected after 16 months. Lesions were large enough to be seen macroscopically after 20 months. by contrast, when the guinea-pigs inhaled chrysotile fibres which were mainly shorter than 3 p. they showed but little reaction to the dust; only scattered phagocytes and an occasional minute asbestosis body were observed. Cellular accumulations about terminal bronchioles were visible microscopically after 2 years, but no abnor mality was sufficiently gross to be detected with a hand lens. There was a slight increase in reticular tissue, but no true fibrosis in the tracheobronchial nodes after 30 months. Chrysotile fibres in the size range 20 50 p arc evidently pathogenic. The conclusion that particles less than 3 p long arc relatively harmless must be drawn with some reservations because of the experimental difficulties encountered in the tests. Vorwald showed that strictly comparable dusty atmospheres containing asbestos of different 154 ASM-STOSIS fibre lengths could not be produced. The average values (Table 12.2), which arc taken from the detailed control analyses of the atmospheres, emphasize the degree of variation to he expected in experiments of this type, even when the most careful attention is given to technique. The deductions made from the results of inhalation experiments arc supported by those obtained by intratracheal injection. Long fibre (20-50 p) chrysotilc will produce the cellular reactions in the lungs of guinea-pigs which were described earlier; there arc foci of cellular proliferation after 1 month and well-developed areas of fibrosis after 12 months. When the administered dust particles were below 3 p in size, they evoked an initial,proliferative reaction Taiii.f. 12.2 Differential Cminis (perenila/'e of loltil count) Non-fibrous Fibrous Analysis < 3|x 3-10 n "> 1Op > 10 p Chryso Serpen tilc tine 10p Clumps (per cent) (per cent) Long fibre . 05-4 Short fibre (hull tn ifled) . 90-6 1 -1 4-8 0 25-8 10 0 0-8 0-6 10 3-2 60 IS 20 60 and the dust became localized about the bronchioles but after 12 months there was no considerable fibrosis. There were only a few microscopic patches where the alveolar wall was thickened, and some adenomatoid change in air spaces adjacent to thickened bronchi. No asbestosis bodies were observed. It has been suggested427 that particles which are smaller than the critical size are removed by macrophages whilst those above this size do not reach the distal air spaces. King and others44" obtained rather different results when asbestos of graded fibre length was transferred to the lungs of rabbits by intratracheal injection. The long fibres (15 p) produced a nodular reticulinosis, comparable with experimental silicosis, but the short fibres (2-5 p) also produced a reticulinosis. Effects of different types of asbestos and other fibrous partic.les.-- Vorwald and others440 found that inhaled serpentine, of particle size less than 3 p, when injected intratracheally induced simple phago cytosis in the lungs of guinea-pigs but that it had produced no fibrosis 1 year after the experiment commenced. When administered by intratracheal injection (dose 50 mg.) the fibrous minerals chrysotilc (Thetford and Arizona), amosite, croci- liXI'liniMI-NTAl. ASllliSTOSlS 155 dolile (Bolivia and S. Africa) and tremolitc all produced fibrosis about the bronchioles. Hrucitc, MgO.ILO, produced a similar reaction. In all eases asbestosis bodies were formed but often they were not observed until after the fibrosis was well established. Kundius and IJygdcn431 found that "asbestosis" bodies formed around rutile needles. Anthophyllitc, another fibrous mineral of the amphihnlc group, produced no fibrosis. After I month scattered intrabronehiolar dust foci were observed but after 8 months there was little evidence of dust. Lymphocytic infiltration of the bronchiolar walls, giant cells, and a few atypical asbestosis bodies were seen after a month. No explana tion of the inert character of this asbestos has been offered. (Hass wool was also inert. Giant cells collected the particles, which could be seen as fine spicules in the cytoplasm, and formed clumps in the peripheral airspaces. No fibrosis was visible aftera year. Progress of lesions after discontinuance of dust exposure. Guineapigs were exposed to an atmosphere containing asbestos dust for periods of 6 or 9 months, then kept in a normal atmosphere for periods up to 3 years. The initial cellular reaction to the dust was replaced by thin strands of fibrous tissue 8 to 11 months after exposure ceased. As the fibres matured, they contracted so that the amount of scar tissue decreased with time. Experimental asbestosis docs not, then, progress after the animal is removed from the dust-laden atmosphere. Relation between asbestosis and tuberculosis.-- When guinea-pigs which had inhaled asbestos dust for 2(> months were transferred to a normal atmosphere and then infected with tubercle bacilli, the course of the tuberculosis was not appreciably altered. When the infection was coincident with the onset of the exposure to dust, the results were variable; in some animals the disease did not progress, but in most there was a temporary progression and subsequent healing. There is no evidence that asbestos dust significantly affects the course of a tuberculous infection. Aetiology Two theories have been used to explain the damage caused to the lung by asbestos. The one theory,440- 4ab 423 which is supported largely by the results of animal experiments, suggests that the damage is purely mechanical--that it is due to the fibrous nature of the dust. 'I'he following evidence supports this view. Only asbestos fibres which arc more than 20 p and less than 50 p long have been found to cause fibrosis in the lungs of animals.440 Moreover, fibrosis has been produced in the lungs of guinea-pigs by the intratracheal injection of brucitc fibres, which contain less than 1 per cent ,Si02. 15.X AKHKHTUSIK for the normal lungs were subtracted from those from the asbestosis cases, the extra mineral matter appeared to be only silica, lie concluded: " One cannot avoid the conclusion that the asbestos has undergone decomposition in the lung, with deposition of Si02" and lie suggested that the disease is "due to the chemical action of silica . . . liberated in situ from inhaled silicates capable of relatively easy decomposition within the lungs". Asbestosis and cancer of the lung Statistics have been published which suggest that the incidence of cancer of the lung is higher among asbestos workers' than among the general population. Merewether stated in the Report of ll.M. Chief Inspector of Factories,44'1 that carcinoma of the lung was notified in 31 of 235 eases of asbestosis (13 per cent) but in 91 of 6,884 cases of silicosis (1-3 per cent), Gloync430 from personal examinations found carcinoma of the lung in 17 of 121 (14 per cent) autopsies on subjects with asbestosis but in 55 of 796 (6-9 per cent) autopsies on subjects with silicosis. Gloyne emphasized that it is not possible to get figures which arc statistically significant because of the small number of asbestosis cases. The ratio of women to men workers in industries in which asbestos is handled is much higher than in the industries in which silica is used and amongst the general population. Lung cancer is more common amongst men than women. These facts give the figures an added significance. If only the male subjects who contracted asbestosis arc considered, the incidence of carcinoma of the lung is 17 per cent in the group studied by Merewether and 20 per cent in that studied by Gloync. A comparison of the incidence in different industrial groups of carcinoma of the lung associated with pneumoconiosis is made in the chart (Fig. 12.7). Doll448 studied the records of a group of 105 persons who had died after working in the asbestos industry. Of these, 18 had lung cancer and in 15 eases the cancer was associated with asbestosis. lie compared the mortality in a group of 113 men who had worked for 20 years or more in the industry with that in a corresponding group of the general population. Thirty-nine deaths occurred in the one group whereas the expected number was 15-4. The excess was due to lung cancer, and other respiratory and cardiovascular diseases, lie stated: " From the data it can be concluded that lung cancer was a specific industrial hazard of certain asbestos workers and that the average risk among men employed for 20 years or more has been of the order of 10 times that experienced by the general population." lie pointed out, however, that the workers examined had worked in the industry before the pathogenic nature of the dust was rccog- A-SIlliSTOStS AND CANCKIt Ul- Till- l.UNC 159 Fin. 12.7. Malignant neoplasms asso ciated with pneumoconiosis. (After Gloync, J,ancrt, 260, 810, 1051.) nized and before the introduction of the Asbestos Industry Regula tions, 1931, which controlled the conditions in asbestosis factories. Whilst most investigators believe that a relationship is probable between asbestosis and carcinoma of the lung,450< 037 others153' ZM do not. Experiments with animals have shown negative or inconclusive results.451* 452> 453> 454 See also Rombola.030 >*3 PNEUMOCONIOSIS Industrial Diseases of the Lung caused by Dust ' liy p. v. noi/r I'H.D., iMi.i.r., M.r.iuoi.. Lecturer in Chemistry in the University of HcmlinK LONDON EDWARD ARNOLD (I'URUSHKRS) LTD. First published *VS7 ( (\UG26W57^ Made and printed in Great Ilritain by William Clntvet anti Sant, Limited, London and lieccles CONTKNTS Chapter l'aj>e 1 Introduction ........ 1 ' 2 Tin-: Structure and Properties or some Industrial Minerals . .14 '3 Till- CHEMISTRY OF Till- SUREACES OE MINERALS . . 26 4 Tin- Chemistry or Silicic Acid . . . .32 5 Tin- Solubility or Silica and Silicates ... 41 6 The Interaction or Siucic Acid with Tissue Com ponents ........ 52 7 Fibrous Tissue ....... 62 8 Pll YSIOI.OOICAI. AND PaTHOI.OOICAI. KrPECTS OP ADMIN ISTERED Sii.ica in Tissues other than the I.uni; . 81 9 Dust in the Luno ....... 99 10 Siucosis...............................................................................Ill 11 The Soi.uijii.ity Theory or Siucosis . .. .131 12 Asbestosis . . . . . . . .142 13 Goal-miners' Pneumoconiosis . . .. .16(> 14 The Fppects or other Siliceous Dusts .. .171 Kaolin, Talc, Mica, Slate, Felspar, Sillimanitc, Cement and Carborundum 15 The lin-ECTS or Some Non-Siliceous Dusts . . 178 Ueryllium, Aluminium, Iron oxide, Graphite, Calcium car bonate and sulphate, Tungsten carbide, Tin oxide, Uarito, Zircon, Titanium oxide, Calcium fluoride and Organic materials 16 Protective Measures aoainst-Pneumoconiosis . .187