Document pedgOrymDbr5bpMR0pRozxxnE

INDUSTRIAL MEDICINE AND HYGIENE Edited by E. R. A. MEREWETHER CB..CB E,, M.D., KR.C Pn D I.H, F R.S.Ed., Barristfr-at-Law II.M, Senior Mdhal Inspector of Fartokiir, Ministry oi Lamiur ami National Service; Chiff Medical Adviser, Ministry or Agriculture HwHimies and rnoii VOLUME 3 BUTTERWORTH & CO. (PUBLISHERS) LTD. LONDON 1936 SCF-FA-4578 Sfea CONTENTS CKAITER fAUH 1. Silicosis and Othcr Fidrqtjc Pneumoconioscs - -- l A. Melklejohn, M.D., M.R.C.P., F.R.F.P.S., D.P.H. Senior Lecturer in Industrial Health, University or Glasgow; Formerly Member of the Medical Board for Silicosis and Asbestosis 2. Dust Diseases, Excluding Fibrotic Pneumoconiosis - - 123 A. T. Doig, M.D., Ch.B., D.P.H., M.R.CP.(ErL). H.M Medical Inspector of Factories; Lecturer in Industrial Hygiene, University of Aberdcon. Formerly Medical Superintendent, Oalcwood Hall Sanatorium, and Tuberculosis Officer, Rotherham Industrial Carcinogenesis and Toxicology Par r i * Occupational Carcinogenesis - Part n. Some Aspects of Industrial Toxicology M. W. Goidblatt, C B.E, and Judith Goldblatt 185 36ft Index to Volumes 1-3 v DIAGNOSIS OF PNEUMOCONIOSIS to be observed the first is the patient's reaction to the effort of undressing and dressing; this constitutes a simple exercise-tolerance test; secondly come the general build, so maUc type, chest configuration and nature and range of respiratory movements. The development of the soft tissues of the chest wail and, particularly in the female, the si2e and conformation of the breasts, should be recorded, for theso items are often important in the inter pretation of the radiograph. Percussion, auscultation and percussion.--By reason of the insidious onset and the paucity of physical signs, pneumoconiosis has been described as a silent disease. Percussion and auscultation frequently, in the presence of well-established changes, suggest no abnormality, yet on the other hand, in another group of cases, one may discover the whole range of abnormal physical signs. Even when massive shadows appear radiographically, precise areas of dullness cun seldom be mapped oul by percussion, whilo, despite the evidence of morbid-anatomical changes, clinical signs of pleurisy and bronchitis are the exception rather than the rule. Cyanosis Classicully, cyanosis and clubbing of the fingers are regarded as regular accompaniments of chronic pulmonary disease, and so one would expect evidence of these in pneumoconiosis. Slight cyanosis is very difficult to define, even by the most careful inspection, and quite often it is present only in the imagination of the physician. It can definitely be asserted that easily recognizable cyanosis, except when associated with serious cardiac embarrassment as in cor pulmonale, is seldom observed in pneumoconiosis Asbestosis, however, is exceptional, for in this variety of chronic pulmonary fibrosis, unmistukuble cyanosis of the malar regions, lips and lobes of the ears is not uncommon, while drumstick clubbing of both fingers and toes is almost pathognomonic of the discaso, in workmen employed in certain processes in the manufacture of asbestos textiles. Diagnosis of clubbedfingers Clubbing of tbe fingers, too, except as just mentioned, is a rare manifestation (Fig. 13a). Any enlargement of the terminal phalanx is, by many people, mistakenly regarded as clubbing. In many artisans, who, in the course of work, are required to apply pressure with the tips of the thumb and fingers, the pulp of the terminal phalanx often becomes considerably broadened and thickened. This spatulate appearance Is not clubbing. Clubbing generally appears first in the thumb and index finger and later involves the others. When present m asbestosis it usually affects both hands symmetrically. The first changes are observed at the root of the nail, where thickening occurs and the overlying skin becomes shiny and injected. In this area the circulation is impaired and, in advanced cases the defect may actually impnrl a dusky blue coloration. PNEUMOCONIOSIS OUf TO GRAPHITE ANIJ SOOT 105 Manufacture of artificial graphite Artificial graphite is prepared by crushing, grinding and calcining of gas and oil cokes, and is used in the manufacture of shaped carbon blocks and electrodes for use in electric furnaces in the production of aluminium metal This material is a very pure form of carbon, and the silica content seldom exceeds 1 per cent of the total weight. It has been proved, and accepted for purposes of industrial disablement benefit, that labourers employed in the milling operations suffer from pneumoconiosis similar to that found among workers in natural graphite. In Great Britain, soot, lamp-black or " nearly pure carbon " is manu factured commercially by the incomplete combustion of gas and tar oils and petroleum distillates Mineral impurity constitutes only a trace. The chief uso of this product is us a reinforcing filler in rubbor-compoundmg. Tn addition to producing rigidity in the vulcanized rubber, the carbon increases the tensile strength and the resistance to abrasion. No definite evidence of pneumoconiosis, in either the lamp-black or the rubber industry, has so far been recorded in Great Britain, but Brauss and Gartner (1951) have recorded tho occurrence of cases in Germany. A similar product--gas-black-is manufactured in America by burning natural gas, which is 95 per cent methane. This work, it is reported, does not cause any pulmonary disease. Recently the writer has observed a few cases of simple pneumoconiosis among a group of workmen in the north of England who were engaged for many years (30 to 50) in the manufacture of soot (no silica impurity). Cause of coal and graphite pneumoconiosis These observations arc important in relation to the aetiology of pneumoj coniosis of coal-workers The problem is whether these cases of pneurao! coniosis arc due to the small amount of silica within the coal or graphite or j are due to the carbon itself. That there is no simple answer to this question ' will be realized, if one recalls that the pathological changes in the lungs may be determined, not only by the quality of the dust, ohemical and physical, but also by mere quantity of fine particles, while both factors may be further influenced by associated infection ASBESTOS1S Asbestos, meaning unconsumable, is a collective term applied to a group , of silicate materials, which, while differing widely in chemical composition, i resemble each other in certain valuable physical properties. They are finely i fibrous in structure, and so can be split readily to microscopic size without ' loss of identity. Single fibres have been noted up to 43 inches and down to 0-000003 inch in Jonglh. The fibrous structure, which, in varying degree, is associated with flexibility, enables it to be spun into yarn and then woven E3-200S 07:08P FROM: TO:1S18259 >06 Stl ICOSIS AND other FIBROlIC pneumoconiosis into textiles. The following are Ihc special qualities of the material which make it of use in Industry; (1) resistance to fire and heat, (2) low hcatconducltvity, (3) high electrical resistance and (4) inertness to chemical action. Varieties of asbestos The several varieties of asbestos fall into (wo main groups; (l) chrysntile, or serpentine asbestos, and (2) amphibolc asbestos, which includes (a) amosile, (b) crocidolile and (c) tremolite Chrysolite Chrysolite asbesros, which constitutes 90 per cent of world production, is a hydrated magnesium silicate. The fibres are short (usually a fraction of an inch), very fine and of a silky sheen. Thetford (Quebec) Is the chief source of supply; lesser quantities urc obtained in Southern Rhodesia, the U.S.S.R.. and elsewhere Amphihole Amosite contains iron from which it derives a dirty brown colour. Deposits or this variety of asbestos oceur almost entirely in South Africa. Normally the fibres are several inches long and of poor spinning quality. Accordingly, its main use is for the manufacture of heat-insulating blocks, and as a binding mulcnal in the composition used in the production of asbestos cement sheets, which are nowadays so extensively used in the fabrication of modern houses and other huildings | Crocidolile, or blue asbestos, occurs mainly in the Cape Province of South Africa, and in the industry it is usually designated " Cape Blue It is extensively used when resistance to chemical action is required. 1 Tremolite asbestos is obtained from Italy It is white and the fibres may exceed a yard in length Because of undue brittleness, it is not suitable foi the manufacture of cloth, and so is chiefly employed for insulation purposes, such as the lagging of boilers and steam pipes. Mining and manufacture of asbestos Mining The minoral is obiumcd cither in open quarries or in shallow mines, and the normal operations are drilling, blasting, breaking and sorting When, freed from waste rock, the asbestos is dried and successively crushed to a fine powder. Foreign matter is removed by screening, and particles of iron arc extracted by passing the material over powerful electric magnets. The crude fibre Is then graded according to length of fibre, and is packed for despatch to the manufactories. Manufacture Asbestos textile manufacture is similar to that of other fibres, such as v hich leat- e nical '! )dlcr a isite. , is a if an i; *of 5 5.R., :| osits r ially i igly, 1 as a it sstos ti m of I outh . It is si may b e for r oses. a, and Vhen x to a o 'Iron s The o d for n eh &s asbwtosis 107 cotton, wool and flax, first the fibres are opened in a Crighton machine, then follow in succession carding, spinning and weaving All these opera tions, unless carefully controlled, produce considerable amounts of fine thistledown dust, which is wafted far and wide throughout the factory premises and even into neighbouring buildingR, including adjacent offices. Water, or even wetting agents, so useful in the control or dust, are of no value because asbestos is practically unwell&ble The cloth is used for the manufacture of fire-protective clothing* suits, helmets and gloves, and safety curtains. It is sewn into covers which, when filled with crude fibro, form mattresses or pads for the insulation of heating boilers, tanks and pipes. In the form of tape, it is very easy of application for the protection of domestic pipes against either frost or heat loss. Bonded with bitumen it is moulded into slabs for use as panelling, or cut and shaped into brake-linings, gaskets and other forms of packing for machines. Jn the manufacture of cement roofing-tiles, fiat or corrugated sheeting, rainpipes and other building materials, asbestos is introduced into the " mix '' as a binder. During World War II, small quantities were incorporated into the cotton-wool filters of gas-masks Waste asbestos boarding is often crushed and used as a filler in paint manufacture. The importance ot this reference is that very frequently the workmen in these processes do not know the danger, which is aggravated by an almost entire lack of safety precautions. The main centres of asbestos textile manufacture in Orcat Britain are at Rochdale, Leeds, Clcckheaton, Barking and Glasgow. History of asbestosis in 1906, Montague Murray reported the case of an asbestos-worker, who had died in the Charing Cross Hospital in 1900 of " typical fibroid phthisis ". The man, a card-room worker aged 34 years, had stated that 10 of his work-mates had died at about the age of 30 years. Sporadic cases continued to be recorded, and finally in 192b Seiler reported on a case, which seemed definitely to establish the relationship between the inhalation of usbestos dust and disabling and fatal pulmonary fibrosis. Therefore the Home Office instituted an official inquiry into the asbestos manufacturing industries throughout Great Britain, and the report by Mercwether and Price remains the authoritative account of the disease (See Mercwclhcr, 1930.) The occupational origin was proved, and accord ingly asbestosis was recognized as a compensatable disease under the Work men's Compensation (Silicosis and Asbestosis) Act of 1930. in addition all workmen employed in certain scheduled occupations were required to puss an initial examination, and thereafter, at yearly intervals "Since extended to 2 years--to submit to periodical medical examination. Any workman found at such examination to be suffering from asbestosis was immediately sus pended permanently from all further work in the processes FEBH23-B00S 07:09P FROM: TO:1618S5 IOK MUCOSIS AND OTIICR FIOROTIC PNEUMOCONIOSES Patholog i and morbid anatomy of asbestosis In cru ihing operations, fiberizing and disintegrating, in opening, spinning, weaving and the filing of asbestos mattresses, production of fine thistledown dust occurs This consists of fine needles nr spicules of asbestos, which are inhaled by the workmen Most of the dust inhaled never reaches the lungs, bpt Is arrested in the upper respiratory tract and trachea, from which it is rejected in the nasal mucus and sputum Whereas only the minute parljiclcs of silica gain entrance and are retained within the lungs, much larger particles of usbestos, when mhulod, because of their physical form, arc mechanically trapped. Fibres up to 200 microns have been delected in the air passages, but dangerous fibres measure up to 20 microns. In the lung no local necrosis results, nor is there any leucocytic reaction. As a result of mechanical irritation the pulmonary epithelial cells are desquamated, and fibroblasts appear round bronchioles and alveoli, in interlobular septa and in the subpleural tissue. Finally, collagenous fibres appear around the distal raraificajtions of the bronchial tree. Gtardner and Cummings (1931) have shown, by animul-inoculniion ex* perimems, that the chief site of asbestos-dust localisation is the respiratory bronchiple. They describe the curly lesion, in the guinea-pig exposed to inhalation of asbestos dust, as follows: " The asbestos dust is carried by the Inspired air only to the distal respiratory bronchioles . . . The mononuclear phagocytes from the adjacent connective tissues enter the lumen of the air passages and engulf the particles. ;The|phagocytes with their contained fragments of dust are frequently pushed nsidc into the alveoli which pouch out of the sides of the bronchioles, where many of them remain Indefinitely. More dust entering the lung is held up by the partial obstruction created, and further reaction is largely proximal la ihc point of original localization." At 60 days the authors describe the dust-cells of the terminal bronchioles as being increased, and the lumina of some of the lateral alveoli completely blocked with mononuclear phagocytes und giant cells At the end of 2 months small asbcslosis bodies appear. After 90 days' exposure it was found that the amount af cellular reaction had not kept pace with the number and size of the asbcslosis bodies Hyperplasia of the lymphoid tissues was now visible. At the end of a ypar the wails of the bronchioles proximal to the alveolar ducts were thickened fijom excessive local accumulation of phitgooyies, but definite proliferation of fibroblasts was not noted until after 550 days. This was confined to the walls of the air spaces adjacent to the deposlli or dust phagocytes. Ai ihe end of n further 100 days a true fibrosis developed, contracting the air spaces, which now appeared to be filled with compact masses of dust cells and phagocytes, fibres and bodies. After 2 years the mischief had reached the periphery of the lung, and sub-pleural greyish-white nodules were uniformly distributed over the surface. King. Clegg and Roe (1946) have recorded the results of experiments in rabbits exposed io the inlriuruchcnl injection of usbestos fibres of varying length. In P:6'13 animals treated comparable wji with short fihia of powdered al Post-mortem app Microscopicalji> The morbid ap above for siljeosi The pleural chm of pneumoconio advanced long-st sheath like a pla folds, and it io frequently the \ completely obliti as is shown on p The asbestosis fibrotic charactei Ftc. 19.--Fern lung showm theTower pol Dt II Wyi 590896 the a of fetal cent qles. shed here 1 up imal ssas . eked small i bunt m rtosis 3 of a c ;ened t m of < walls U of a /hlch i bbits Q In f ASBESTOS1S 109 animals treated with long fibres (15 microns) a nodular xcliculinosis developed, comparable with iho experimental silicotic nodule, whereas in animals treated wjth short fibres (2-5 microns) a diffuse reticuljnosis appeared. The addition oj powdered aluminium did not afford any benefit in either group. Post-mortem appearances Maeroscopicalfindings The morbid appearances to the naked eye are very similar lo those described above for silicosis (see p. 23). No specific change occurs in the air passages. The pleural changes, however, are more marked than in any other variety of pneumoconiosis. Generally the pleura is everywhere thickened, and in advanced long-standing cases iho lungs appear encased in a glistening yellow sheath like a plastic material. All over the pleura is puckered and raised in folds, and it insinuates itself universally into fissures and sulci. Not in frequently the whole space between the visceral and parietal pleura is completely obliterated by massive tough sessile adhesions. These changes, ns if shown on pago 115, dominate the radiographic appearances. Tjbe asbestosis lung is firm and airless, and when it is cut with a knife the fibrptic character Is immediately apparent. The characteristic lesion presents .tffljirVsaS Piir. 19 --Female aged 35 years Asbestos spinner 5 years Posi-mottcm section of lung showing blue-black polygonal areas of asbestosis and thickened pleura. At the lower pole a squamous carcinoma surrounds an abscess cavity (By couruiv of Or H Wym) 1 -13-2006 07:10P FROM: TO:1618259 MO SILICOSIS AND OTHER FJBROTlC PNEUMOCONIOShS as bli;o-black polygonal areas J-i inch in diameter. These are distributed over ho whole of the cut surface, but arc most evident in the lower lobes. This pay be due to confluence or simply to the greater bulk of the base of the lung. Anatomically it will be observed that these polygonal fibrosed areas conform to the sue and shape of the pulmonary lobules, which they have, in fact, replaced. All these changes may be considerably modified according to the terminal illness* broncho-pneumonia, tuberculosis, bronchial carcinoma or con' gestiye heart failure. Other organs do not show any characteristic changes, they are not involved in the disease save indirectly and in relation to complications and sequelae Microscopical up/tearances Asbestos fibres (natural and altered), plugs of mucus and desquamated epithelium may be observed in the maJn air-passages la ihu terminal bron chioles and alveolar ducts, these changes are more advanced and associated with the presence of large mononuclear phagocytes. The alveoli and lymphutio vessels are blocked with dust und phagocytes Connective tissue surrounds the bronchioles, alveolar ducts, air-sac$ and blood vessels, and penetrates into the interlobular septa and beneath the pleura. In the most advanced stage, all appearances of lung structure are obliterated by fibrous ! tissue, i | The ashestosis body I Curious bodies in the lungs were first described by Stuart McDonald in 1927. They are now recognized as a feature of exposure to the inhalation of asbestos fibres, and they have been identified in the lungs, pleura, sputum and faeces. It Is now accepted that they are formed from the original fibre by the following process: (1) deposition of some material around the fibre so as to thicken it; i (2) fissure or cracking of (his material giving rise to the appearance of 1 segments; (3) fragmentation, or the separating off from the asbestosis body j of fractured portions of the deposited material. Oloyne (1932) summarizes , the variety of uppearanees hs follows. i (1) Marked variation in length (24-60 microns) and breadth (12-24 p). Gardner and Cummings (1931) record iheir being as long as 250 p in experi mental animals The short forms arc sometimes seen within phagocytes. (2) Golden yellow colour: Gardner and Cummings have pointed out the resemblance or this colour to the haemosidcrin deposits found in areas of tissue in which haemorrhage has occurred. (3) Homogeneous structure when viewed by ordinary transmitted light. | (4) By cutting down the light, a suggestion of a central fibre can often be \ seen. This fibre may also sometimes be seen projecting beyond the body, i (5) No dilTcreniiarion with polarized light. I (6) Tendency to be arranged m irregular clumps and clusters ASBESTOSJS I Fxa. 21.--Asbestosls bodies In sputum; white blood cells Indicate comparative size. 07:IIP FROM: TO:161825908 1J1 SILICOSIS AND () IHLR F1BROT1C JPNtUMOCONlOSBS (7) Very early Terms unsegmemed (" sausage-shaped "). (8) Later forms crennted, segmented, or resembling a senes of oval discs, or beads strung together in a necklace form. Sometimes, later, a short length of fibre is seen between the segments. (9) Bulbous or pointed extremities (or one bulbous and one pointed suggesting " heads and ttuls"). Slnuon and Siruohun (1931) have noted sharply nnglcd forms suggesting incipient fracture, and beheve that the tapenng tail forms may be the broken ends of this fracture (10) Generally quite straight, occasionally curved, very rarely S-shaped During examination in a wet preparation, slight pressure on the cover slip will sometimes cause them to bend owing to tho elasticity of the central fibre. This proneness to bend under stress and strain may explain the curved forms often seen In sections of lissuo, as suggested by Gardner and Cummings. (11) Forms seen " end-on '' look like knobs or door-handles. Small secondary knobs and bosses sometimes seen thereon. Histological technique. - -Gloyne (1933) describes the following technique for the identification of these bodies: After digesLion of the sputum with equal quantities of concentrated antiformin and centrifugation, the nntiformin is pipetted off, and the deposit covctcU with a small quantity of a 5 per cent solution of ammonium sulphide The asbesiosis bodies are then coloured blnok. This colour can he removed with hydrochloric acid. Sections. --In the case of sections the following technique has been found useful: After removal of the paraffin wax with xylol and alcohol in the usual way, the section is washed with water and then flooded with ammonium sulphide, which is allowed to remuin for several minutes. The section is next washed and counter-stained with an aqueous solution of neutral red, dehydrated, and mounted in balsnm. This method of stauiing also shows Ihc presence of n large amount of iron in the sections. Unfortunately the black colour is slowly removed by the mounting fluid, and the sections will only keep for a few weeks. Staining with haematoxylin--Hacmatoxylin, which ulso has an affinity for iron, can be made to colour asbestosis bodies, but it is rather a deposition of stain than a true staining reaction. The technique is as follows. After digestion of (lie sputum with equal quantities ot concentrated unliforniin and after centrifugation, the anliformin is pipetted off and replaced by a 5 per cent solution of Ehrlich's haematoxylin. Blueing or Lhe hnemtuoxylin immedi ately takes place owing to the remains of the alkaline anliformin. The mixture is well shaken and allowed to stand for jr-1 hour, and then centrifuged again tuid the depom mounted as a wet preparation By this means the asbestosis bodies become a dark-brown or black colour, according to the length of time they have been exposed to the hoemaioxyltn. Although these haematoxylm-coloured bodies give the impression of having the haematoxylin deposited on them rather than having actually taken up the stain, after washing over-night they still retain sufficient stain to give a darkbrown effect under transmitted light. ASBtSTOSIS 113 Diagnosis of asbestosis While the methods of diagnosis Follow those for the pnoumoconioses in general--namely, occupational history and clinical and radiographic investi gation--the relative value of these items is unusual and so merits comment. Occupational history Reference is made on page 107 to the authoritative contributions made to our knowledge of asbestosis by Morcwcther and others 20 years ago. At that time the industry was comparatively new, factory conditions were not good, and neither employers nor workers realized the dangers of the material and the processes. The typo of workman was poor and the labour turn-over was heavy. The great majority of cases, when diagnosed, were in the advanced stages of the disease, and tho symptoms, clinical signs and radio graphic changes were correspondingly severe. Furthermore, by present standards the technical quality of x-ray films was unsatisfactory, with the result that radiographic interpretation was not always reliable. Meantime, conditions have substantially altered for the better, and patients present themselves for diagnosis at a much earlier stage--indeed, sometimes before tho disease has had time to develop. Despite increased knowledge and experience of the disease and the higher standardof radiology, a firm diagnosis in the earliest stages is still often extremely difficult Another matter worthy of note is that, in the spinning, weaving and asbestos-mattress sections of the industry, the workers are predominantly females, but doctors outside the immediate locality of tho factory seldom associate dust disease of the lungs with women, particularly young girls This is further complicated by the fact that the disease may not become manifest until the woman has married and left work, and her occupation is then designated as "housewife1'. Pregnancy--especially in the later months--is sometimes the circumstance which aggravates any dyspnoea and leads to investigation of the cause. Furthermore, early radiographic changes in asbestosis are usually most marked in the lower halves of the lung fields, and the female breasts, when engorged in pregnancy and occasion ally during menstruation, may obscure these changes when present, or simulate them when they do not exist Howover, by reason of the great publicity which the disoase has attracted in the main centres of the industry, the workman usually announces the diagnosis to the doctor, who himself is equally aware of the local scourge. Nevertheless, even without this guidance, any doctor should be aware of the possibility, provided that he has investigated the occupational history in the manner described. Clinical aspects of asbestosis Dyspnoea is the single universal complaint, and it is all the more con spicuous because frequently it is quite out of proportion to the clinical signs 07:IIP FROM: TO:161825 114 SI) ICOSIS AND OTHER FlBKOflC PNEUMOCONIOSES tn the longs Considerable emphasis has often been laid on the showers of persistent fine crepitations, which are particularly audible over the bases of the lungs. These adventitious sounds are intrapulmonary, but they do not necessarily indicate disease, for they can be detected within a Few weeks of commencing work and without any accompanying departure from health. The most probable explanation of their occurrence is that they arc due to obstruction of the bronchioles by usbestos fibres, and this is supported by the simultaneous appearance of altered fibres in the sputum. The presence of true asbestosis bodies in the sputum is not diagnostic of the disease; these bodies merely indicate that asbestos fibres have been inhaled and retained sufficiently long in the lung to acquire the characteristic changes. Stewart (1933), however, has expressed the opinion that clumps or fibres may denote disease associated with breaking-down of lung tissue. This observation is analogous to the occurrence of elastic tissue in the sputum in tuberculosis, and of persistent " black spil" in tholate stages of massive fibrosis in silicosis and pneumoconiosis of coal-workers. In advanced cases all the clinical signs of lung fibrosis may be detected, and they are usually associated with evidence of cardiac distress. Apart from dyspnoea, two features are impressive: (1) an earthy cyanosis and (2) the sudden appearance of an extraordinary degree of drum-stick clubbing 1110 22 Norm'll chest radiograph Female, aged 24years; married. Note obscuration of basal lung fields by heavy breast shadows, ASBESTOSIS IIS Fio 23.--Male as^d 49 yean (1953). 1926-38, asbestos millboard cutter; 1938-43, timekeeper and gatekeeper; 1943 el stq., despatch clerk Typical radiographic appearance* of advanced asbestos!*; dabbing of fingers Ute Fig. 13). At present working regularly. (By courtesy of Or, IT, tt'yrrr) of the fingers and sometimes of the toes. Out or Wyers' series of S3 con secutive cases, clubbing of the fingers was present in 29 cases (Wyers, 1949). Complications of asbestosis.--Pulmonary tuberculosis occurs as a com plication, but there does not seem to be the same close relationship to asbes tosis as exists in silicosis. An excess mortality from cancer of the lung and olher organs has been recorded by several observers. Wyers, the medical officer to a large asbestos manufacturing company, stated in 1949 (.we Table V) that he had collected details of 1 IS deaths from asbestosis, and that of these cases 11 males and 6 females showed pulmonary cancer, whilst cancer of other organs was present in 3 males and 4 females (in the pancreas, colon, stomach and ovary). Despite the frequency of dubbing of the fingers, frank infective bronchiectasis is unusual. Congestive heart failure and broncho pneumonia arc common terminal conditions. Radiological appearances in asbestosis Often the first fact which impresses the reader is the smallness of the chest, as if tho lungs were shrunken from apex to base. The next feature Is a general haziness of the lung fields; this has been described as veiling or a FROtjl: TO:16182590896 1)6 | SILICOSIS AND OTHER K1BROPIC PNEUMOCONIOSES ground-glass appearance. While there is no orderly progression of changes, the next stage is characterized by fine mottling or stippling, localized or general, and particularly conspicuous in the lower halves of the lung fields. This mottling may later become coarser, thus producing a granular pattern. Thereafter the whole picture is dominated by the sclerotic pleurisy described on page 109 Thu costo-phrcnio and cardio-phrenic angles are obscured, and the outlines of (he cupolae of the diaphragm and of the cardiac shadow appear shaggy, because of opacities, which, as so aptly described by Wycrs, resemble teused-out cotton-wool. In some cases a very characteristic appearance is presented by the horizontal fissure, which is thickened and presents a lenticular rather than a fine linear shadow, It is also often con siderably depressed in level, especially laterally, so that instead of appearing horizontal it is oblique, with the convexity directed upwards and outwards. Ii Differential diagnosis it cannot be said that the condiuon requires to be differentiated from any other condition. If the investigation follows the routine which is outlined, almost complete accuracy should be achieved. It may be said, however, that, ml the early diagnosis of asbestosis, aR a supplement to the occupational history, tho clinical features are a more reliable guide than radiographic changes and, indeed, often precede (hem. Incidence of asbestosis In Great Britain the risk of contracting the disease occurs in the asbestos manufacturing industries, and to a small extent in heat-insulation work, pjpc and boiler covering (lagging) and the other incidental processes, such as stripping the old composition. The risk varies, of course, with the dustiness or the process and, in the absence of efficient dust suppressing and collecting devices, the most dusty operations are (1) preparatory processes of crushing, opening, sieving, mixing and blending, (2) sack filling and emptying and all hjandling of loose usbestos. (3) carding and card cleaning and grinding, (4) cloth weaving, (5) matlress making, and (6) cleaning dust settling or filtering chambers Jn recent years considerable advances have been made ifi controlling the dust at the source of production. Thus, whereas in 1929 cases were identified after 7 years' exposure--some even after u much shorter period--the corresponding figure now is 10 years. I <r k i. ( s. >y a at f ic IS )S a k, h as iq ss ^ig ill i ig> I or i do 3 29 c ;er d *y { ne OTHER SILICATES CAUSING PNEUMOCONIOSIS 117 envisaged before. In this connexion the dictum of the Committee that " For practical purposes the conditions arising from flyer spinning carried on without exhaust under good conditions may ... be taken as the `dust datum ' "* was agreed, and this level of dust production was accepted as tho basis on which to assess the dustiness (and henco the necessary protective measures) of other processes. Nothing has emerged to suggest departure from This practical standard. It should be remembered that ring spinning is more dusty than flyer spinning, and therefore local exhaust ventilation should be applied to ring spinning. Doubling, plaiting and braiding may be linked with flyer spinning in this connexion. At one time prohibition of the industry was advocated--a completely futile and absurd attitude, as is proved by the present importance and development of the manufactures A sub stantial measure of control has been achieved by mechanization and by enclosure of machines with Perspex panels. As a means of safeguarding the health of workmen in dangerous processes, the statutory system of initial and periodical medical examinations by the pneumoconiosis Medical Panels is in operation. This medical supervision i i supplemented at most large factories by the work of the firm's own factory medical officer. OTHER SILICATES CAUSING PNEUMOCONIOSIS f].part from asbestos, silicates do not constitute a serious cause of pneumo- Tjooiosis among workmen. One important reason, of course, is that the population at risk (excluding the clay industries, bricks and tiles) is small. Sporadic cases, however, have been reported, and certain relevant facts arc Iorthy of note. Silicate minerals exist in two forms: (l) fibrous, which includes (a) sbestos, (6) talc, (c) sillimanite, and (d) sericite; (2) non-flbrous, Including r) mica, Qi) china and ball clays, and (c) Fuller's earth. Talc and French chalk Talc is hydrated magnesium silicate, and in its compact form is known as ! teatite or soapstone, which is familiar as the chalk used by tailors for i larking doth. The purest talo deposits occur in association with dolomite i nd marble, and the chief sources of supply are the United States of America i nd Manchuria. Talc exists in fibrous and plato forms, and the special ualjtics which make it valuable in industry are low conductivity to heat and lectriclty and resistance to fire: hence its use In insulation. About 90 per t of the talo production is marketed in ground form, us a white powder, hich is used as a filler for paints, distemper, paper and soaps. Popularly it is best known os toilet powder and as a dusting agent (French chalk) in .the manufacture and handling of rubber. * Report oa Conferences between Employers and Inspectors concerning Methods for Suppressing Oust tn Asbestos T isUlc r.cinrtes, H.M. Summery OfRen I9JI. 16P FROM: TO:16182590896 164 OU$l DISEASES, EXCLUDING THE HBR0T1C PNUUMOCONlOSGS a impounds, at least, must be added to the list ot' substances which may cause cancer of the respiratory tract. Association of pulmonary cancer with silicosis and asbestosis Between 1930 and 1940 there were several papers calling attention to a suspected association between lung cancer and silicosis, the inference being that silica might, directly or indirectly, play some aetiologies! part in producii g the malignant disease. Such an association has not been borne out by farther inquiry. The relation between asbestosis und lung cancer is, however, quite different. his subject is dealt with in Chapter I of this volume New and unknown Industrial carcinogens In the future there may be new and increased usage of certain materials now known to be carcinogenic. This is true ul the present lime for radioastive,materials, especially isotopes, and tor x-rays. Furthermore) as our Knowledge of the aetiology of malignant disease of the respiratory tract increases, it is to be expected that other materials which are now oncounlored in the industrial environment, as well, perhaps, as some in the domestic environment, will prove to have carcinogenic properties. New uses for some ojf the rarer mcluls ure continually being found and the toxicology of many or these is incompletely known. Substance* carcinogenic to animals.--Some substances, not yet known to produce cancer in human beings, have been shown to induco malignant changes in animals. Beryllium is one of these, intravenous injections having been reported, both in Oroat Britain (Barnes, 1949) and in America (Gardner and Heslington, 1946; Dutra and Largent, 19S0), as causing sarcoma of bones. Animal experiments have also shown that selenium is carcinogenic for certain species, although no human caso attributed to its industrial posure is known. TMineral oils. -Uncertainly exists about exposure to mists of mineral oils, epcounlered by garage workers and in other occupations. Kennaway and I^ennaway (1936) note that spinners and piecers of cotton, who are exposed to fine droplets of mineral oil, have a very low ratio (31) for lung cancer, but a rather high ratio (148) for laryngeal cancer. Hueper (1951) mentions /re-propyl oil, as requiring further study in regard to cancer of ihe nasal sinuses and lungs, in tho manufacture of /re-propyl alcohol. Santo (1949) summarizes available knowledge concerning the reaction of the lungs to the instillation of various types of oil. He says that mineral ails may produce net only acute lipoid pneumonia but chronic granulomatous infiltrations or paraffinomas. He presents 2 cases of bronchial carcinoma in patients who had been taking liqdid paraffin dally by tho mouth ovor a period of years. In 1 case organizing lipoid pneumonia was present throughout the affected area, and in the other the carcinoma appeared to have arisen in such an ASBESTOS 21S , there was 1 milligram per gramme of nickel in the long even 8 years after cessation of exposure. If Loken's results were correct, there must have been 'some 1-2 grammes of nickel in the lungs--a wellnigh incredible figure-- , completely out of harmony with Bames and Denz's conception of non retention unless there was very great difference, as seems likely, in the physical form and states of the nickel. ASBESTOS The association of what appears to be purely mechanical trauma with a later development of neoplastic change has a long history both in the ex perience of myriads of medical observers and in that of theorists who invoked it in the exposition of a theory of cancer. If such an association is looked at askance it is not because it is denied that it can occur, but rather that it is too facile and even sterile an explanation. Of the tens of millions of mechanical traumas occurring daily, the number which can be later recognized as having possibly initiated a neoplastic process in situ is minute. Most pathologists would sum the matter up by saying that if trauma is followed by the develop ment of a tumour at the site of the original trauma, then that site was not normal at the outset. . Co-carclnogenesls The classical experimental basis for the effect of the super-imposition of trauma on an abnormal site is the Deelman phenomenon. Deelman showed in 1923 that if a tarred area of animal skin Is injured by wounding or other physical effect, tumour formation might be hastened and its location thereby determined. This observation was later confirmed by other workers who used pure carcinogens and laid the foundation of what is now called co ' carcinogenesis. Co-carcinogenesis may be defined as the augmentation of the action of a carcinogen by some suitable additional treatment which shows itself in increased numbers of induced tumours and/or shortening of tho induction time. In general the term co-carcinogenesis is applied to an effect produced by local application of an agent to a tissue (Borcnblum, 1947). A co-carcinogen is not itself a carcinogen although Anderson (1948) appears to think otherwise, regarding co-carcmogene$is as a synergy between sub liminal doses of two or more carcinogens. Such mechanical irritation as strongly brushing the skin, and foreign body fibrosis, have been shown to be effective as co-carcinogens, heat, cold, radioactive radiations, croton oil and resin, all possess co-carcinogenic power. The precise nature of co-carcmogenesis is difficult to understand except as an expression of certain experimental facts. The significant matter from our present viewpoint is that Tor a co-carcinogen to produce its effects it must be applied after a preparation of the tissue has taken place by a carci nogen, or even after an overt carcinogenic response has regressed. Although the whole conception of co-carcinogcnesis has arisen from fpEQ.b3.200t 07:16P'FR0M: TO:16182590896 :5'13 216 INDUSTRIAL CARCINOOHNESIS AND TOWCOLOOY experimental work on mouso and rabbit skin, some such idea must be evoked by a problem such as that of asbestosis and cancer, until some more experi mental evidence of direct carcinogenesis by asbestos or a decomposition product) or u can be obtained. Tf such an idea is feasible, then we must also assume p pre-neoplastic preparedness in the organ in which the co-carcmogcn (usbestos or the fibrous tissue in the peribronchiolar reaction) later induces u further development into true neoplastic growth. The preparedness of the tissue if it is to be regarded as more than a form of words is brought about by something independent of the asbestosis, and this must be regarded us an endogenous factor. But some special property must also attach to the asbesto! is foi the alleged cancer Induction in this condition is not apparently found in the long-stunding cases of silicosis- We will firpt consider the evidence that asbestosis leads in a proportion of cases tc camper of the lung. As long ago as 1938 the suspicion arose that asbestos workers might be more than normally prone to lung cancer. Nordjnarm (1938) analysed six cases of lung cancer and showed that the range of exposure periods was 7 21 years, and the rango of intervals between entering the industry and death was 13 to 21 years The malignant disease in some cases occurred years after leaving the industry. Half of these cases were co nparauveiy young, 33-41 years of uge at death. In one remarkable case a 11-year old woman had worked in asbestos for only 19 months. Later in the'same year he referred to a further seven cases of associated asbestoi is and lung cancer, including Gloyne's (1936) finding of six cases of carcinoi aa of the lung in SO necropsy cases of asbestosis. Tn tic 1947 Annual Roport of the Chief Inspector of Factories, Merewether [tabulated the age incidence among 235 deaths caused by asbestosis: in 13*2 per cent or these cancer of the lung was present, and it is especially imporlunl to note that 4*8 per cent of the age-group 25-34 years and 5*6 per cent of the age-group 35-44 years had this condition, ll will be seen that the over-all figure is closely in agreement with Gloync's findings. In a further report* carrying this analysis up to the end of 1934, be found tipat amongst 344 deaths, in 55, or 16*0 per cent, cancer of the lung was present. In their senes of papers on asbestosis Lynch and Cannon (1948) give an analysis of the post-mortem examination of 40 cases of asbestosis among which 3 case,s of carcinumu of the lung were found associated with medium or advanced grades of asbestosis, which, according to these authors, is seven times tha general incidence in the United States. In a r tore recent study of the clinical picture and pathology of asbestosis, Behrens (1952) estimated that of 309 cases of asbestosis reported in the literature there were 44 cases of carcinoma of the lung (14-2 per cent) whereas in a senes of 2,204 cases of silicosis only 32 such tumours were found ( *4 per cent). * Annual Report Chief Inspector o! Factories Tor 1954, pp, 190-195 he discrepancy 1 ijder, as that found 'SL'jpTgSgWes*t.i,v-e. * as thei with th< Jffbatfjime which Snesof'235 cases c bichds again .almi series of Saffibing.the c JvcHpg.pipeswitl wearing a respiratc ^Irugh nothing not '"s'bone marrow. ^shadows whi ___ r ^tumours. aftered large not ffical3 examinatio ^astic .carcinoma udbe some doubt Jpfmuthors incline Igftke problem of i suggest that pect of its com] fkjless eomprorr Sadly that in ' about 1J-20 yet jiblished in the ^.'successfully c vea^sofworkina! ^aWgraphic invei *"frer lung field . Middle ahd lower Lobectomy of fatihiziiig squai yasToccupied by i now. Asocsto ^ph node. Rec xpansion of the 1 jfti'suggestive ca H^years.who 15 jlustry. Necroi jcinoma accom uthor is cautious ASBESTOS 217 The discrepancy between the two incidences in Switzerland is of the same order as that found in the smaller series by Lynch and Cannon In the United States. Suggestive as these and other data are, Stoll, Bass and Angrist (1951) were dissatisfied with the statistical woight ono could put upon available figures at that time which included, in addition to those of Lynch and Cannon, a series of 235 cases of asbestosis with 31 carcinomas of the lung (13-2 per cent) which is again almost identical with the finding of .Behrens. They refer also to another series of 115 cases with 14*8 per cent lung tumours. Describing the case of a worker who had been engaged for only 6 years covering pipes with asbestos and who had refused to take precautions by wearing a respirator, they point out that except for weakness and persistent cough nothing noteworthy was found unlil malignant cells were found in the bone marrow. Radiographs of the chest showed numerous large discrete oval shadows which were interpreted rather as metastatic deposits than primary tumours. Post-mortom examination showed asbestosis with scattered large nodules and metastases in kidneys, brain and liver. Histo logical examination confirmed the presence of asbestosis bodies and ana plastic carcinoma of the lung, with numerous metastases. There appeared to be some doubt about the primary focus of malignancy in this case, and the authors inclined toward a multiple origin. Whethor this case is relevant to the problem of asbestosis cancer is open to question, but the authors were led to suggest that asbestos must itself be regarded as a direct carcinogen in respect of its composition as a silicate. A less compromising attitude is taken by Werber (1952) who states cate gorically that in 7 -17 per cent of cases of asbestosis after a latent period of about 1$-20 years, as a result of epithelial metaplasia, carcinoma becomes established in the lung. Werber then reports what appears to be a clear-cut caso successfully operated on. The paiicnl was a man of 58 years who, after years of work in asbestos with complaini of irritant cough, showed, in a mass radiographic investigation, a well-marked dense round shadow in the right lower lung field associated with bilateral finely granular shadows in the middle and lower fields, more marked on the right side. Lobectomy of the right lower lobe confirmed the presence of a non keratinizing squamous cell carcinoma. Nearly the whole of the lower lobe r was occupied by an almost certainly bronchogenic (postero-lateral segment) . tumour. Asbestosis bodies were found in the lung and in an excised hllus .lymph node. Recovery was uneventful and x-ray examination showed later ` expansion of the upper and middle lobes. A suggest!vo case is also described by Curcton (1948) of a young woman of 37 years who 15 years before had left asbestos work after 7 years in the industry. Necropsy showed a predominantly squamous-celled bronchial carcinoma accompanied by asbestos bodies and fibrosis in both lungs. This author is cautious about the relation between the neoplasm and the asbestosis 0116 218 INDUSTRIAL CARONOClfcNfcSIS AND TOXICOLOGY bui po ins oui lhac the woman was very young for a squamous growth. As in the case of most other occupational tumours, it is commoner to find worker] without the neoplastic reaction than with it, even after all the upparci tly necessary and sufficient conditions Tor its development huvo boon found t > exist. Many such cases have been amply described. We give one or two rom |he Continental literature. ' Havii g wcjrked for 22 years consecutively applying insulating (asbestos) materia to articles, a man aged 40 years was killed in a street accident, never h iving complained of respiratory troubles. Franchlni and Cancpa (1949) j erforjmed the post-mortem and found a frncture of the base of the skull as the immediate cause of death. The lungs were massively and exten sively fiirosed mainly in the middle and lower lobes, with lymphocytic infiltrati ms and thickened elastic tissue: many asbestosU bodies were found occupying the lungs and lymph nodes. No mention of neoplastic change is made. Ijt is spcciuliy interesting that, us in so many other cases, tho massive pulmonary changes should have been unaccompanied by complaint. This is of importance because if after a period of exposure to asbestos dust a certain measure of fibrosis is developed and thereafter the industry is left, Mye may picture a static non-symptomatic, non-progressive fibrosis, but a continuing process of cancellation in a certain number of cases Whether the preceding fibrosis is necessary for the subsequent neoplastic process or whether the latter is conceivable without the former, it is not as yet possible to say. The entry of any particles or fibres into the lung, even when they are soluble in water, produces a phagocytic response from the septal cells in the alveolur walls and giant cells with many nuclei soon develop. In the case of a soluble compound the ultimate degeneration of the dust cell permits the second stage of the absorption of the compound. This is readily shown ex perimentally with any of the common laboratory animals. The lung presents a temporary barrier to soluble particles; in the case of insoluble particles the barrier is more permanent, depending on tho size of the particles. The smaller particles may be taken up by phagocytic cells arising from various sources qnd disposed of in lymph glands, in the interstitial tissue of the lung and even to some extent in organs- from which they cun bo excreted Every thing depends upon the size. Phagopytic I cells may, however, be completely frustrated both by the nature and size of particles. Tn such cuses they surround the foreign matei ial and a process of local fibrosis sets in, the foreign unattackablc material remaining me re or less m situ. a[ small pailide (2-3 micrograms) will ultimately enter the alveoli and the | fibrpus rpacuc a will start from the alveolar walls and lymphaucs, if it cannot otherwise be disposed of. If the particle is big (10-15 micrograms) and cannot therefore proceed into the ultimate air passages, it is held up and the reaction o xurs more proximally in the broncbiolar tree ASBESTOS 219 In respect of the basic features of the body's reaction to asbestos fibres there is nothing to choose between them and particles of silica. The par ticular differences, which are undoubtedly observed, arise from different 'physical form; difference in solubility; difference in size, and the possible (.difference in carcinogenic properties. The term asbestos is vague and industrially may refer to any of a series ;-of complex silicates. It belongs to a group of crystalline magnesium silicates, which include talc (steatite) MgsH4(SIOi)4, Meerschaum Mg,H,(SlO,),.HtO, . possessing varying degrees of resistance to heat and to chemical agents. It is best as recommended by Spencer (1937) to preface the word asbestos with ' the particular mineral from which it is derived, for example serpentine ^asbestos and amphibole asbestos (hornblende). Unfortunately, more t words than one are used in this industry for the same natural product. ' The common forms, with country of main origin, used in the various ^.industries with which our present theme is concerned are: \ (1) Serpentine asbestos (Canadian) (chrysotile*; amiant). Chrysotile is the most used of the fibrous silicates. Empirical formula: H,Mg,Si10, ,L(=3MgO.H1(S.O,)s). As mined tho following is the analytical composition of an average sample ;'of the naturally found mineral (serpentine: hydrous magnesium silicate); SIO, AI.O, FeO Fe,0, MgO HtO per cent 43 0 52 10 41-36 13-79 ; (2) Amphiboles Empirical formulae: ijCajMg^SiOj)* Tremolite (Italian) i,Ca(MgPe)t(SIOa)4 Asbestos (amphibole asbestos)' (CaMg,(SIO,)4 Actinolite '^N3gFe''Fe,'"(SiOj)e Crocidolile (Blue asbestos--South Africa, Australia) (3) Amosite asbestos (South Africa) (ferro-anthophyilite). Empirical formula: H.,(MgFo),(SiO.,)a. Their commercial value is due to the long fine, infusible, non-conducting bres in which ihcsc silicates exist and can be worked and it is this char- which motivates the characteristic changes in the lungs when inhaled ver considerable periods. In the mining of serpentine and of the asbestos it as a mass of fine, silky crystals In Canada, Cartier (1949) found that "could divide the 3,242 workers of whom 40 per cent had been in the : for 10-40 years into two groups, one exposed to the dust of serpentine, i remained free from asbestosis and the other, exposed in grinding, 'Not *0 te confuted with thmolirc which j* in Uomurptmux mixture of vita). (furiieme) and PaSiO EB- 23-201 i 07:18P FROM: TO:161 !20 INDUSTRIAL CARCINOGENESIS AND TOXICOLOGY awning, suction and bagging to the dust of the dried separated fibrous lllcate, in which all the cases of asbestosis developed. Among (ho 22 cases if ashes to is found by'radiography and confirmed post-mortem, there was to mentio i of any cases of cancer of the lungs. More clinical and occupatonal dau on these cases would havo been desirable. On the basis of the ladings el iewh^re, 1 or 2 cases of lung cancer would have been expected. 3n the ex] eriraptal side Carrier implies that his clinical data are confirmed >y exposui e of pnimals to the two kinds of dust. Cartier nakes two statements of considerable interest as to the severity >f asbesto is among his miners. (1) Dur ng hjs 3 years of clinical observation (more than 10,000 complete nodical e> animations) no worker has died of uncomplicated asbestosis under the age of SO years, even after 20-30 years' severe exposure to asbestos dust; nor has h< seen among asbestosis cases as severe cyanosis or dyspnoea as thatiseen n asthmatics, lung cancer or advanced tuberculous cases. From this'he cc ncludcs that pure asbestosis is not as severe a diseuse as it is considered in Great Britain and elsewhere where manufacturing processes are canted out with the separated asbestos. (2) Pure asbestosis, often even radiologically very advanced, is found among workers who show no clinical signs, no diminution of respiratory function ajtd can without discomfort carry out ihoir habitual tasks. The claipn by Cartier amounts to this, that asbestosis as usually described is really a mixed disease, complicated by cardiopathies and even tuberculosis, and that " pure " asbestosis as seen by him is by no moans a severe condition. Having been in close association with such notable authorities as Gardner and Vorwald, these statements cannot be ignored because of relatively short experience of the industry. It may be that Cartier considers a life of 60 years amply sufficient for the relatively few cases who develop the disease severely enough to die from it. He does not, however, in this paper give the popula tions at risk so that we cannot calculate essential data It may be relevant to his thesis that the population around the Thetford mines is almost entirely pependent upon them for their " gagne-pain ", Cartier's second statement is, however, borne out by the case of Franchini and Canepa. It will be recalled that whereas the general view in Gteat Britain is {that the symptomatic picture is more severe in asbestosis than in silicosis, the reverse view is held in America. The long period of absence of symptom^' has, been known for many years, but the diminution in vital capacity demonstrable even when the worker is perhaps unwilling to admit any respiratory abnormality. As was pointed out over 20 years ago by Mcrcwcther and Price (1930) and Mereweihoc (1930), the worker is inclined to attribute his discomforts to causes other than his work. A more normal case history is that given by Luton, Champeix and Faure (1951) who describe what is slated to bo tho first case of asbestosis reported in France This was a man aged 62 years who, having worked for 11 years E! IS B7ilSI ;10^13 ited ibrou d c xupa-1 3asis of the] ex tected. coi&nnedl [he $tverity I i co ipletol tosis under) dust; ipndea as' From] it is | prcfcesses is bund itory des< ribed iosis, lUUliion. ' as Ga dner atively short eof60 rears sase sc brely the pc nila ' be rel vant aostei irely 'I >f Frai iw in/ osis fabsen l<j l in | nj to i >ajs * i i incttned f id F iurc repc rtcd n > ars ASBESTOS 221 in an asbestos cloth factory (2-25-4-Ox 10B particles (1-2 p) per litre of air) complained of dyspnoea on exertion and was somewhat cyanosed. Radiographically the fibrotic condition progressed in the middle and lower lobes until he (tied 7 years later. Necropsy findings were of the classical kind; diffuse fibrosis, thickened plurae, no nodulation, many asbestosis bodies with giant cells and many mineral particles in the lungs. Dust particles were found also in the vessels of the liver, kidney and spleen. No mention is made of metaplasia or nooplasdo changes. These authors discount the possibility of a chemical influence of asbestos particles on the pulmonary tissues. Wc have been at some pains, but without success, to elicit any statement or evidence in the literature of asbestosis which could be interpreted as more than ft verbal attribution of the dlocls of asbestos particles to irritation. For the fibrotic effects there does not seem any reason to seek causes other than sharp " insoluble " foreign bodies larger than a critical size. The work of King, Clegg and Rao (1946) in which they pursued the mechanical action theory of Gardner, presented a reasonably full picture of the response of the lungs of rabbits to insufflation of small (2-5 p) and large (15 p) asbestos fibres. Gardner and bis school had emphasized that, as we havo already mentioned, with asbestos particles size is everything, small particles being innocuous, big panicles hazardous, and that this distinguishes their effects from those of silica and quarts which are entirely the result of small particles. Nevertheless, King, Clegg and Rac did find some effect from the inhalation of small (2-5 p) particles of asbestos, which might be described as a diffuse fibrous tissue reaction affecting mainly the interstitial tissue and alveolar walls with hyperplasia of the bronchial- nodes and some nodular areas of giant-cell reaction. Phagocytosis of these small particles was probably easy enough to restrict the reaction to the locations mentioned. With larger fibres (15 p), the foreign body giant-cell processes were apparently overlapped by a more permanent reaction, nodular in distribution, which fixed the asbestos particles in situ. King, Clegg and Rae mako the significant comment that these nodular, somewhat acellular, areas of intra-alvcolar connective tissue were strictly comparable to, if less intense than, those produced by quartz, which means that the lung does not distinguish them. In respect of small particles they suggested that if fibres < 2-5 p in size were insufflated, they would be completely removed from the alveolar wall and fail to produce interstitial fibrosis. Tt scorns possible (hut in the case of Luton and his colleagues the smaller particles were phngocytosed and discharged into the circulation in the way probably envisaged by King and his co-workers, since they report having found dust particles in the vessels of the liver, kidney and spleen. Summing up the many years of research of Gardner and his co-workcrs on the effects on animals' lungs of asbestos particles administered by 1-23-2006 07: IS3 FR0|1: TO: 1618259^96 222 INDUSTRIAL CARCINOGENESIS AND lOXIOOLOOY inhalation, intratracheal insufflation, intravenously or intr&pcritonc&lly, Vorwuld, Durkan and Pratt (1951) recall that ordinary industrial (asbestos) dust apd, especially, long fibre asbestos dust from which (he small fibres had been separated, produced characteristic peribronchiolar fibrosis which remained static on discontinuance of exposure, whereas to particles of 3 n and lep there was no tissue reaction (King, Clegg and Rae, 1946). On substituting Brucilc (native magnesium hydroxide containing only 0-9 per ccit silica as silicate--Brucile is a crystalline compound easily split into tb n sheets and has a flexibility comparable to that of asbestos fibre), for the asbestos peribronchiolar fibrosis is similarly established, but dust of glass fit rc which is not flexible and, of course, cannot be split docs not, on long imal&tlon, lead to fibrosis. The dependence of the fibrosis on physical form was, however, settled by th s failure to induce fibrosis by long inhalation of asbestos which, having been fused and ground, no longer retained its original structure. The {Gardner school held that the combination of size, physical form and in mobilization in a rhythmically moving organ is the determinant of the pa ihogcnic effect. Effects somewhat similar to this pulmonary fibrosis can be obtained by iqjection of asbestos fibres into the peritoneum. But jat no stage in all these impressive researches was any clue obtained wi tich 'might have offered any support to the possibility that asbestos could ac t as a carcinogen. There is no reliable criterion by which one can anticipate carcinogenicity and, as is well known, relatively minute changes in the structure of a chemical carcinogen are sufficient to diminish or eliminate ca reinogeme action. If apbestos is indeed to be regarded as a carcinogen, tho need is felt to demonstrate some property which can be regarded as something more than inprtnps. The simplest such property Is solubility. Solubility confers some activity on a compound as, for example, in -the case of silica, the solubility ol' which in aqueous conditions is sufficient to found a chemical theory of si icosis. Asbestos has, however, not given much evidence of a solubility which night be significant. In analysing the working environment for asbestos dust Sundius and Bygden (1938) made the curious remark that only amphibole asbestos could be recognized in their analyses, in spite of the fact that the asbestos commonly used in indusiry contains mainly chrysolite und to a considerably lesser extent amphibole asbestos. This statement, if confirmed, might mean that chrysotile Is dissolved in the analytical process. In fact, chrysolite is the least resistant of asbestos types to chemical and physical agents' it is decomposed by hydrochloric and sulphuric acids, it loses water at red heat and its fibres can be fused in the bunsen flame. (Crocidolilo--blue asbestos--is also fusible to a black magnetic glass but is resistant to chemical agents). I Assuming that chrysotile might be capable of exerting some chemical P:11'13 effect by vir to the ashes have some: structure ir experiment: bodies did Cooke ( made the f spicules up soluble fra salt, have alveoli In recent in the elec that Cham the aetiolo Electron m The pro the electro the photo Cbampe Alkalii 10 minut Homo cautiousl Decan To ex; . To exi micro-m of the ol ` fracture ,, As rega |microscoj yith the ijways > nyelope ffipressio pisiform < - Two ol i6. fibres collo SSiipula &were h< ' aesc ITK ' ASBESTOS 223 effect by virtue of these and perhaps other related properties, the mind turns to the asbestos body which, lying in the lung tissues for long periods, might have some significance other than that usually attributed to them of being a structure in which the enclosed asbestos fibre can lie innocuous. In the experiments of Gardner and his school the injection of isolated asbestos bodies did not produce fibrotic reactions. But this need not deter us. Cooke (1930), who, with MacDonald, discovered the asbestosis body, made the following comment: `` they consist of central nuclei of asbestos spicules upon which colloidal aggregates of blood proteins, plus, possibly, soluble fractions of asbestos, and, in the case of chrysolile workers, iron salt, have been absorbed and moulded by currents in the bronchi and alveoli In recent work Champeix and BoutevlUe (1950) examined asbestosis bodies in the electron microscope at magnifications of 25,000. It may be recalled that Champeix was associated with the view opposing a chemical factor in the aetiology of asbestosis (Luton and his colleagues). Electron microscopy ' The procedure to examine an object as delicate as an asbestosis body in the electron microscope presents much difficulty, and the Interpretation of the photographs obtainod should be correspondingly cautious. Champeix and Bouteville treated expectorated material as follows: Alkaline digestion of the diluted sputum with NaOH (equal volumes). After 10 minutes' warming in a porcelain dish, allowed to cool. Homogenized fluid divided among several centrifuge tubes and centrifuged cautiously to avoid disintegration of (ho asbestos bodies. Decanted and residues spread on several slides. To examine in the optical microscope, mount In Canada balsam . To examine in the electron microscope the smear allowed to dry and with a micro-manipulator a single asbestosis body is lifted on to the collodion membrane of the object carrier. This operation is difficult and delicate and the hazard of fracture of the asbestos body is great As rogards the general morphology of the asbestosis body, the electron microscope confirms in greater detail and without deformation the findings with the optical method--the central, needled fibre (-1 p thick, length always > 10 p) surrounded by an amorphous, somewhat opaque rounded envelope (2-3 p thick) in parts appearing as if burst and giving a general impression of a colloidal, proteinous gel: the extremities ovoid, ellipsoid, fusiform or sometimes angular. Two observations suggested solution of the asbestos fibre: (1) there were no fibres less than 10 p in length in any asbestosis body; (2) removal of the colloidal envelope of the asbestosis body by means of the micro manipulator shows the central fibre with one edge semi-transparent as if it were being dissolved away. These facts lead the authors to some dubiety on whether the fibrosis is 19P FROM: TO:16182590886 224 INDUSTRIAL CARCINOGENESIS AND TOXICOLOGY due to a maintained mechanical irritation produced by the insoluble amphibolc, or to a chemical effect brought about by the dissolving silicate. Tt may be recalled that Alden and Howell (1944) stated that amosite needles are capable, where embedded in epithelial tissue in the skin, of eliciting a non inflammatory epithelial proliferation. This statement was made from obser vations on amosite workers who developed hyperkeralotic epithelial thicken ing after penetration by a small splinter-like fibre. X-ray examination and biopsy show no evidence of a foreign body in these " corns Solubility of asbestosis bodies More work is required on this problem especially quantitative studies of the solubility of asbestos types in a variety of conditions, together with an identification of the products after solution. The question is not one of explaining fibrosis of tho lung by a chemical process, for this is ulmo&t decisively negatived by the undoubted fact that tbe smallest particles of asbestos have not in fact produced a fibrosis In the experience of most investigators. The question is rather one of finding a product of solution which, by entering the modified squamous epithelium of the lung, or by changing its environment, can lead to de-dilTerenliution or to tumour for mation. The majority of pulmonary tumours in men are anaplastic or undifferentiated or (epidermoid) squamous epitheliomala and they con stitute a type of new growth in the lung which has hitherto eluded the experimentalist. Probably the only claim to have induced a true cancer in the lungs of mice was that made by Nordmanrt and Sorge (1941) who exposed 100 mice to undefined asbestos dust and stated that 20 per cent of the animals developed cancer. There is considerable doubt, however, whether the evidence presented i$ really acceptable. In fact, cancer of the lung (truly so called--not adenomas as found and induced in mice) has not hitherto been produced by inhalation of any material W H Smith (1952) in a very forceful consideration of the experi mental aspects or cancer of the lung concludes " that wc are singularly illequipped for the experimental study of one of the chief problems of human cancer ", Until this charge is successfully answered we may for practical purposes regard asbestos or u derivative ot asbestos as a probable co-carcinogen in that proportion of cases of diffuse fibrosis of the lung m which the necessary preparedness of the lung has been brought about, probably endogenously Such a view has, ill Icust, the merit of loss sterility than the common panacea for carcinogenic dilemmas, irritation AROMATIC AMINES Of tire few identifiable chemical agents which may without doubt be accepted as standing in the line of causality of particular types of human neoplastic disease, certain aromatic amino intermediates in the dyestuffs industry occupy the most interesting and, from tho point of view of the experimentalist, the most fruitful position. Not only have they been repeatedly reported in 3-200$ 07:08P FROM: trtHicul gra shite INDEX Artificial gra shite, 3, 10! Atheresderulic dementia Artificial hit oidlficatton, temperature ami. 2, carbon disulphide 105 polsumng, In, 3, S2I AnHtdal Hgl ting, 2, 308 job onalyn is and. 1,318 Aromk energy, medical services and, 1,1^ Atoms, lonlzatiou or, 2,387 Artificial rta] ib-atlon dectric.il rreplraiion and. 2, 324 dew tnctlu ds, 2, 223 I Atopic allergy, 3,390 ( Atropine, unit-muscarine action, 3,480 Asbestos <- j Attainments, worker selection and, 2, U1" amoSiCe,3 219 * amphlbolt, 3, 219 g / . carclnogei ssls and, 3,215-224 1/ , dost of, l, 31 V ^ Industry, i igulatlnn* applying, 1, 33 v > regulation , young persons and. 1,43^ serpentine 3,2l9\/' Asbestosis, 3 10! body. 3. I 0. Ill| ^ _ compliant ms of, 3, l IS oyanosii ir. 3, 33 \S diagnosis, I, (13 *" history, 3,107 Incidence, 1,116 ^ morbid an itomy, 3,108 ^ poswnnrtc ti appearances, 3,109 *"' prevention 3,116 -- - I Audiogram diesel engine work and. 2, 350 gunfire and, 2,348 ' examination of personnel und, 2,363 gramophune, 2, 365 . pistol firing, 2, 351 pure tone, 2, 364 riveting, 2,350 < Aurnmliiv, cnrelnogcnesis and, 3, 240 ` Aureomydn actinomycosis, in, 2,28 i anthrax and, 2,29 ] Austin Mulor Works, rehabilliatlon and, l i Auto-sensltlxatton, skin alkrgy and, 2,48>s Auxochrome, 3, 248 pulmonary cancer and, 3,164 i Avidin, biotin and, 3,447 Ascorbic aclr AxInMIow fans, ventilation in. 2,294 blood Tom atton and, 3,465 oxidase, 3. 441 ! Asa component, immunc-scra antibodies aq Vase*, glandt re Contracted from, 2,31 Azo-dMsobutyroilinUrltc, 3,424 ksdaunts, sli ip | alopecia ar rata and, 1. 222 diabetes ur d, I, 223 duties or, 1,218 1 Azo dyes lU I cross*sensitiration phenomena and, 2,v I sulphonuniide sensitisation and, 2, StU Azo-protcIns, 3, 434 electrical giads, stiles, I, 218 epilepsy In, 1,222 ' Axoxy benzene, 3. 260 eyesight an 1,1, 221 foot deifccu. 1, 222 gyoaecolog cal conditions and, 1. 223 luuards, 1, 220 heart disease and,11,222 mental characteristics or, 1,223 morbidity, 1,229 Bacillus anthracic, incubation period, 2,: i Huron ! calorie value or, l, 350 mortality, 11,228 vitamm cuntent, I, 364 neuroses inj 1,221 permanent hoods salec. 1,217 personal appearance or, 1, 222 pharmacy, i, 218 selection on 1,222 , Bacteria airborne, removal of. 2, 288 ' respiratory disease due to, 3,167 i Bacterial allergy, 3, 408 septicaemia! In, 1,228 Bacterid, pustular, industrial disease, i _ skin conditions and, 1, 221 snobbish aspects, 1, 23,5 ' from,. Baelcrlnlyaln, mechanism ol. 3,385 , special events, effect of, 1, 218 I special skills In selling, 1,217 1 suicide rale11, 228 Bapacsosls, 3, 168 { Baghdad boll, 2,33 ! techmuuc of selling. 1,217 ' temperament of, 1,223 varicose veipt and, 1, 222 \ women's clothing, selling of. 1, 217 Asthma Tur dyeing and 3,4|9 1 Cuiuuma kamani causing, 3, 181 Bakehouses basemenL, legislation and, 1, 20 welfare regulations, 1,35 I "Baker'sItch",2,37 Baking, bread, skin disease and, 2, 74-76J 1 BAL, chronic pneumonitis, in. 3,157 p-phcnylene| diamine causing, 3,417 platinum sensitization, in. 3,411 vegetable dt sis and, 3,181 Banana, calorie value or, 1, 330 Barberry bush infection, 2, 35 vegetable gi ms causing, 3, 429 Barber's nuh, 2, 34 Netv.--HTeotm u Wd type refer to Voltim* numben [3661 P:l'13 bltone Parbltone, 3, 551 2 B Barium j jb duct, Inlialation, 3,139 j[` sulphide, eye irritation ana? riey, ealorio value of, 1,350 t,--rrler creams & brucella eruption and, 2,36] &. " Camralld *, 2. 85 d dermatitis and, 2. 84 'A effectiveness of, 2,86 essentials Oi, 2, 85 ' grades of substance, 2,85 , oil dermatoses and, 2,73 * JBwytosK, 3,139 S Basement bakehouse-,, 1. 20 ' j' District Councils and, 1,52, (Bdsie deg, pneumonitis of, 3, 1 t` Basophilin, punctate, in lead poi SyBeans, caloric value, 3. 330 v K*` Bents ", coal-miner's, i, 17l| Beauty parlours", work in. 1, jL Bed-bug, infestations, 2, 37 a k Beef, vitamin content, 1, 364 g Beer, calorie value, 1,350 1 (.Belt forks, legislation and, 1, 23 Benches, cleanliness of. t, 13 - TiButds } production of. 2,178 symptoms ami signs, 2,180 , t Benefits '> death. 1,338 pneumoconiosis disablement, . workmen's compensation and, gj.Bcnzaldchyde, skin tolerance, pa . 1, 2 Benzanthracene, 3, 315 `'Benzene chlor-nitro compounds of. skin sensitiratit poisoning, 1, 342 legislation and, 1,38 methionine in, 1, 375 vluimln C in, J, 375 Benzidine careinogenosis and, 3,257 tumour induction, 3, 2J2 Benzine, eye injuries and, 2, HO J' Bcnzocnlne cross-vrnsitizution and, 2, 50 sulphonsmide sensitization and Benzoic add, skin tolerance, paid Beozonitrlle, 3, 509 ^Benzoyl choline, 3, 485 peroxide, dermatitis and, 2, 74 Benzpyrene air concentration, 3, 310 pitch cancer and. 2.63 ^.Benzyl * benzoate, Tronibiailar mfescatio cyanide, 3, S0 fNOtffy--n*