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dm. Omm Mi* VL ||, m. UV-m. Pna IIU. Prim* m OmI Brittle ,< A ' \lf I2.U. '`(c,lcjr-cjnc^c 194 4+ . ASBESTOS BODIES AND MESOTHELIOMA* J. Stumphius Royal "de Scheldt" Ltd., Flushing, The Netherlands P. B. Meyer Research Institute for Public Hcilth, Engineering TNO, Delft, The Netherlands (Received 21 February ]968. in recitedform 24 April 1961) Abstract--The relation between exposure >o asbestos and the occurrence of neoplasia is reviewed and it is concluded that the increasing use of asbestos will result in an increasing incidence of tumours. It is known that inhalation of asbestos fibres results in the formation , of asbestos bodies in the lungs. Typical asbestos initiated tumours--pleural and peritoneal mesothelioma--were found at an unusually high frequency in shipyard-workers. Only slight asbestos caposurc had taken ' place in these eases. On the other hand the persons involved had been eaposed to high . concentrations of iron oaidc (flame cutters and welders). Objects similar to asbestos bodies > were found in their tunp. Originally it was thought that these were pseudo asbestos bodies. containing an iron oaidc core, and it was suspected that pseudo asbestos bodies might play a - part in the genesis of the tumours. Investigations carried out at TNO institutes') showed that the kernel of the bodies contained asbestos of the amphibole type thus proving that they were not pseudo but normal asbestos bodies. The simultaneous caposurc to low eoneemra* lions of asbestos and high concentrations of iron oaidc raises the suspicion that iron oaidc might be an important cofactor in the genesis of mesothelioma found in the shipyard-workers. Experiments with different types of asbestos and iron oaide. on animals, arc considered to bo . highly desirable in order to verify or disprove this hypothesis. INTRODUCTION In recent years an increasing number of reports about exposure to asbestos and mesothelioma have appeared in medical literature. There is an alarming rise in the incidence of this rare tumour and, nearly always, exposure to asbestos is found. Asbestos--an indestructable material--is mined in increasing quantities, for ever wider use inside and outside industry. Known as a dangerous material, leading to illness and death by asbestosis and lung cancer when inhaled in great quantities during work, it now seems to have a long-term effect when inhaled in minor quantities. The last form may result in mesothelioma. Exposure to asbestos also results in the formation of asbestos bodies. 'Publication No. 297 of the Research institute for Public Health Engineering TNO. * t The investigations using electron diffraction and electron microscopy .were carried out by H. D. Zccdijk, and then with the X-ray microarulyter by A. P. von Rosensticl, both from the Mcul Research Institute TNO. They will report in dcuul about their investigation* in the journal Micro Chlm/ta Acta. (TNO ta the Dutch abbiovtation of "The Organisation for AppUod IdendfleRcMafck In the N*hc* land*".) . STOOI1591 /' i.*. DOW 06874 J. Stumi-iiiuj and P. 0. Men* The frequent finding r.!l over the world of asbestos bodies at autopsy, without distinct asbestos exposure, perhaps indicates a widespread contamination with asbestos, unless there is a possibility of pseudo-asbestos bodies being formed. The relatively sudden appearance of a great number of mesotheliomas in shipyard* workers without definite asbestos exposure, or any sign of asbestosis. together with ii a high incidence of asbestos bodies in the sputa of this group of people called for an I examination of these asbestos bodies which is described in this paper. i ASBESTOS < Asbestos, the well-known mineral with the "thousand-and-one applications", 1 also called "the magic mineral", consists of silicates having a fibrous crystal-structure. The two most important groups are: 1. serpentine asbestos (chrysolite); i 2. amphibole asbestos (amosite, crocidolile). Serpentine asbestos is a silica-magnesium compound; amphibole* are composed of silica and iron. t Magnesium, aluminium, calcium and other elements are also found in amphiboles. Asbestos may be described as a mineral that breaks down into fibres when crushed. The molecular units are very strongly linked together in one direction; cleavage i results in fibres which are sometimes of considerable length. Tnis property, together i with the many other well-known qualities, results in the widespread use of asbestos, in and outside industry, for textiles, heat and electrical insulation, friction-materials i (brake linings), filters, packings, filling material for plastics, asbestos cement, etc. Industrial use started about 1880, especially in the asbestos textile industry. i Nowadays an enormous increase in applications can be seen. To meet the growing worid consumption a 1000-fold increase in output has been required in the last 60 i years. The greatest increase started after World War II. In 1945 the total production was about 0-6 million tons. The total yearly world production it now about 3*2 million tons: 90 per cent is chrysotile, 10 per cent amphiboles. The fact that asbestos is practically indestructible means that an ever-growing \ i quantity of asbestos is descending upon the human community, especially in the i industrial parts of the world. Nowadays in many circumstances there is no other material that can replace asbestos. i ASBESTOSIS i A shadow was thrown over the famous qualities of asbestos when the first case of asbestosis was found (Murray, 1907). \ \ii People exposed to asbestos dust in asbestos textile works showed increasing deterioration of lung function; asbestosis became a well-known professional disease. \ After long, or sometimes short, exposure progressive fibrosis of lung-tissue sett in, with increasing illness leading to death. The development of safety measures diminished exposure in the asbestos textile i industry, but the incidence of asbestosis was olfsct by the increasing use for other i purposes such as heat insulation. 4 ASBESTOS BODIES i It was not until 1924, that Cooke described another case of asbestosis. This case * I i t is as asbc csp< dese asbi the the: nee ma thi: of br< an vi: Pf *F st it ir a c C 1 .t i c/>. Io o 1 I <_n o po DOUI 06875 Without Inon wnlt 'icd. m shipyard* .'gciiicr with ~iled for an . plications'*, il-strucmre. : composed mphibolcs. en crushed. ; cleavage :y. together f asbestos, vmaierials '-t, etc. - industry. i*e growing last 60 iuction about 3-2. -r-growing ally in the i no other , first case ncreasing ;i disease, ue acta 10, :os textile Tor other I ; ! This cate I r \ f Aibcuoi bodies and mesothelioma is associated with the discovery of ile "curious bodies" found in the iungs of a female asbestos textile worker. Since then much has been published about asbcsiosis, especially in Dritain. The "curious bodies" were found regularly and it was Sttwart U929) who described them as "asbestosis bodies", in later literature these bodies, together with asbcsiosis or signs of asbestos exposure, were found regularly. Decause of this fact, the name was altered to asbestos bodies. I towever, for many years the finding of these bodies was frequently considered as pathognomic for asbestosis. The very fine needles in inhaled asbestos dust easily descend the respiratory traet and are deposited mainly in the lower lobes of the lungs. The organism seems to protect itself against this irritating material by enclosing the needle with layers of protein. The deposition of protein start', at both ends; later it is deposited on the shaft In this protein iron is precipitated. Under the microscope the bodies have a brownish-gold colour; with an iron-eolouring they show up as pitch-black objects. The asbestos bodies are easily recognised: they have a typieal dumbell form. Asbestos needles may be very thin: the thickness varies from 0-3-3 i*m and many are invisible under a light-m;croscopc. Since the asbestos bodies are very easily visible, relatively large quantities of protein-iron must be deposited. Exposure to asbestos results in the formation of asbestos bodies, as has been proved in many animal-experiments. They may be found at post mortem or even in sputum when exposure was short and occurred a long time ago. In bodies of long standing disintegration occurs and the bodies then resemble a siring of beads. It seems that this disintegration is not sufficient to enable the organism to get rid of the inhaled asbestos. During the last decade a great number of reports have been made about finding asbestos bodies in the lungs at post-mortem, without known asbestos exposure. Thomson (1963) describes asbestos bodies in 30 per cent of the males and 20 per cent of the females in 500 consecutive autopsies over the age of 15 in Cape Town, South Africa. Similar findings with higher percentages were made in Miami, Florida; Pittsburgh, Pennsylvania; Montreal, Canada; and Milan, Italy. In 1966 Thomson tt at. tried to evaluate the recognition of asbestos bodies in their article "Asbestos as an urban air contaminant". The formation of asbestos bodies results from protein-iron being deposited on the thin asbestos fibres. It is possible that a similar process takes plaee with other inhaled materials and has been reported in connection with coal dust and graphite, pseudoasbestos bodies being formed. Other articles describe similar ferruginous bodies formed around carbonaceous like materials (Cross. 1966). There is a high incidence of pseudo-asbestos bodies in human beings, especially in cities and industrial regions. However, the increasing amount of indcstructable asbestos, used in numerous circumstances, may lead to world-wide contamination of human inhaled air. Perhaps the first symptoms of this mass-contamination are beginning to show themselves and the so-called pseudo bodies are, in fact, normal asbestos bodies. ASBESTOS ANO NEOPLASIA The first suggestion of an association between asbestosis and bronchial carcinoma was made about 1934 (Lynch and Smith, 1935; Cloyne, 1935). Later, in reports from the British Ministry of Labour, more evidence was brought up. .* C-6S J l& M rS -r I .4 * *> t J V% \ 06876 :s J. Stvmtimui mid ?. 3. Mrvex Buchanan (1965) summed up the incidence of nsbextosis and lung oncer in Britain. In the U.S.A., Scukoff et al. (196*) made a retrospective study of 652 insulation workers, with over 20 years' exposure; the follow-up was made with the help of the labour-union administration. Of these workers, 255 had died by 1964. Amongst these 255 the cause of death in 45 cases was a carcinoma of the lungs or mesothelioma. The expected incidence was 6-6. Carcinoma of the digestive tract had caused 29 deaths against an expected 9-4. For other carcinomas the incidence was normal. The incidence of mesothelioma of the pleura and peritoneum was found to be relatively high. Later Sfukoff et al. (1965) found that among 307 ex-insulators mesothelioma was the cause of death in 10 cases. Mesothelioma was tong considered an extremely rare tumour. Many pathologists denied its existence as a substantial tumour and looked upon it as metastasis of a primary tumour elsewhere. Nowadays this rare tumour is more and more widely reported. There is no longer any question as to whether this neoplasm is a metastasis or not: it is a very substantial tumour, typically located in the pleural and peritoneal membranes. Metastasis is rarely seen, except in the final stages. It grows fast, encasing the intestines and lungs, usually without infiltrating them. It is a poly morphous tumour, with many different structures, mostly fibrous alternating with tubular and pnpillar areas; typical clefts may he present. It resists any form of therapy. It became more and more obvious that there was a connection between asbestos and mesothelioma, particularly from the reports from Wagnck et al. (1960) and Nf.wmouse and Thompson (1965), who reported the occurrence of meso thelioma in patients with no known direct contact with asbestos. Asbestos mines or asbestos industries were located in the neighbourhood, but exposure in these neighbourhood-cases was slight There are signs that minor crocidolite intake, especially, may result in mesothelioma. The incubation time may be about 30 years. In conclusion, asbestos exposure may lead to asbestosis, to carcinoma of the lungs and digestive tract and to mesothelioma. In the latter case there may be no indication of definite exposure to asbestos. FINDINGS IN SHIPYARD WORKERS Asbestos bodies Since 1875 there exists in Flushing, the Netherlands, a big shipyard and machine tool manufacturer the Royal "dc Schelde" Ltd. This yard is the continuation of an old navy yard, that has been there for several centuries. The shipyard is the only big industry in this little town. The production line consists mainly of new ships, heavy machinery and boilers. The number of people employed was end of 1967 more than 3100. In March 1962 a 41 years old worker had an accident. He acquired a fracture of the 1 Ith and 12th rib, without any further complications. He was sent home; 5 days later he was found dead. The social insurance fund.requested a post-mortem to ascertain whether there was any connection with the accident. The post-mortem revealed the two broken ribs and as the certain cause of death a pneumonia of the influenza type. The patho logist also found numerous asbestos bodies and amorphous iron oxides in the lungs. however withoi any malignancy In his work In building of the construe ile f eng CO " -H one ehr O am loc -- dt of' inje rep ;ar cn _ UD vt _ 11. boi. .at mostly in the iron is used. Investigat welding-rod I Of course places and c The fact exposure. T In the fo during the g alveolar spu After the that out o amorphous various woi In a gr. their spun Espcci; hot-iron (* tion bet'vr Inhale ISO weidc any trace been expc 06877 oou I I lung cancer in e study cf 63i nude mtii the 1 died by of the lungs or digestive tract ; the incidence rhtoncum was . mesothelioma y pathologists metastasis of a , . more widely s a metastasis .nd peritoneal t grow* fast, It is a polyernating with any form of ion between sGKER cr at. r.ee of meso;tos mines or are in these olite ima<e, out 30 years. noma of the : may be oo { ; t i , 1 I j | -- _' *. , ! j I | j nd machine ntion of an lection line :r of people fracture of me; 5 days .ether there wo broken The patho* n the lungs. \ , * i 1 Asbestos bodies and mesothelioma 237 however without any trace of fibrosis, ia no asbestosis could be diagnosed, nor any malignancy. In his working-life the man had had only a very slight contact with asbestos. In building new ships two kinds of insulation processes are used in the last stages of the construction process. Chrysotile felt is used in the first one for the insulation of pipes in particular in the engine room. The second process is used in particular between walls. A mixture of cement, chrysotile, amosite, crocidolite and water is mixed and injected in the indicated locations. It should be noted that asbestos insulation has never been applied by employees - of the shipyard and that the asbestos injection process is increasingly substituted by injection of polyurethane foam or by the use of glass fibers and mineral wool, in repair yards there is more asbestos exposure because of the breaking up pipeline and boiler insulations during repairs. The man had worked in the yard for IS years, mostly in the first stages of shipbuilding--the construction of the hull where "clean" iron is used. He was a welder; so there had been a heavy exposure to iron oxides. Investigation of the welding-rods used revealed that no asbestos containing welding-rod had ever been used in this yard. Of course exposure to asbestos cannot be entirely denied; it is used in so many places and circumstances. The fact that there was no trace of asbestosis indicated only slight asbestos exposure. The numerous asbestos bodies however called for further investigation. In the following 4 years a great number of sputa of yard workers was screened during the period of coughing after she "common cold" when there is always some alveolar sputum. After the sputa had been concentrated and stained, microscopic research revealed that out of 247 sputa, 147 contained asbestos bodies, mostly combined with amorphous iron. This total attained greater significance when split up over the various work-departments of the yard. Shipbuilding Engineering Maintenance, etc. Administration Total Total sputa 87 SS 40 32 247 Asbestos bodice 63 32 22 1 147 r/j "3 39 33 23 33.3 In a group of 24 insulators 22 (92 per cent) were found to have asbestos bodies in their sputum. Especially in the shipbuilding department a lot of work is done with exposure to bot-iron (welding, burning, etc.). So it might be asked if there could be any connect tion between the asbestos bodies found and exposure to iron oxides. Inhaled iron oxides may lead to harmless sidcrosis of the lungs; examination of 180 welders in the same yard revealed no significant decrease in lung function, aor any trace of asbestosis on the X-ray photographs. However there had sometimes been exposure to welding-smoke for'23 yean or more. I STDOT(595 DOW 06878 i Pit J. Stumphius and ?. 5. Mctu The possibility that the asbestos bodies found could be pseudo-asbestos bodies or ferruginous bodies had to be investigated. Mesothelioma In 1964 the first case of pleural mesothelioma of a yard worker was reported. In the following three years the number of mesotheliomata rose to 21 in the whole province of Zeeland. From this number 17 had worked in the same shipyard in Flushing. Two more yard workers probably have mesotheliomata; these are not yet pathologically proved, but the clinical symptoms arc unmistakable. All pathological work in Zeeland is done by one institute; all cases of mesothelioma of the pleura and peritoneum were correctly diagnosed in biopsies and post-mortems by this institute, sometimes controlled by other pathologists. All cases were concentrated in Flushing and the immediate neighbourhood. In nearly all cases a good occupational history could be obtained. Only 4 cases had never worked in the yard. Of these 4, one had had definite exposure to asbestos; 1 had worked with hot iron (foundry) ano 1 in agriculture. For one no occupational history could be obtained. All were people of 60 years or older, when they succumbed, and it was known that nearly all had had a risk exposure to oxides of iron. In all post-mortems asbestos bodies were found in the lungs; no trace of fibrosis or asbestosis could be detected, even after thorough search. In three other cases asbestos bodies were found in sputum. The question of the nature of the asbestos., bodies found became urgent. In this matter we received great help from the TNO institutes in Delft (the Netherlands). The asbestos bodies were extracted from post-mortem lungs in considerable numbers and thoroughly washed to get rid of most of the organic materials. Ia this form they were presented to the TNO institutes with three questions. 2. The determination of the kernel of these bodies: asbestos or not? 2. If asbestos, what type could be detected in these bodies? 3. If not, what other elements could be found 7 PROCEDURES USED FOR INVESTIGATING THE COMPOSITION OF THE KERNELS OF ASBESTOS BODIES The electron microscope and the "X-Ray microanalyzer" were the main instru ments used during the investigation. Isolation of the asbestos bodies from the samples, which proved to be necessary, was carried out with the aid of a micro-, manipulator. * Electron diffraction utilising an electron microscope The electron microscope offers unique possibilities for investigating the structure -. ir'r of microscopically small objects. This is not only cue to the much larger resolving power of the electron microscope compared to the light microscope (100-1000 times better) but atso due to the possibility of applying ci.Traetion methods on a small selected section of the speeimen under investigation. By the use of diffraction methods, :t irin principle possible to deduce the three-dimensional structure of atoms within the crystal lattice of the surface of the specimen (Beeching, 1946; Ullxian, 1961). From the diffraction pattern, it was possible to calculate the dimensions of the . elementary cell, which indicated the presence of asbestos. Subsequently the diffrao- tion patterns o pattern to be ic The X-ray mict In the class then functions waves generate of selected par specimen secti milted or refle The degree of in a horizont; horizontal mo Tae resolv size of the cr registered by The princi ' electron scan: IciMfa (HI C/> o o cn v> cn 111 l 06879 DOW asbestos bodies or was reported. In j 21 in '.he whole seme shipyard in . these are not yet . Ail pathological ma of the pleura mortem* by this ere concentrated rod occupational ard. Of these 4' at iron (foundry) rained. nd it was known : trace of fibrosis bree other cases a of the asbestos p from the TNO in considerable tateriala. In this u not7 ; j | ` | i ; | ' *[ i Aiistiti jcz'.a and mesothelioma 239 tion pattens of known asbestos types were compared ir. detail with the diffraction pattern to be identified. The X-ray niieroanelyzer In the classical microscope light is projected upon the object each point of which then functions as a light-cmiticr. 2y processing (with lenses) the electromagnetic waves generated by the emitters, a picture is constructed which is a magnified image of selected parts of the object. An alternative possibility consists of the scanning of specimen sections by a beam of light. After amplifieation.-the light which is trans* mitted or refected, is made visible on a display tube by use of television techniques. The degree tff magnification can be controlled by causing a small beam movement in a horizontal direction over the object under investigation to proouce a larger horizontal movement over the electron image display tube, see Fig. 1. The resolving power of this type of instrument depends in the first place on the ` ` size of the cross-section of the beam which must possess sufficient intensity to be registered by the detection system employed. The principle described above is applied in the X-ray microanalyzer. A beam of electron scans over the specimen's surface. The secondary electrons, which an i STOOl159: OSITION he main instruodies from the aid of a micro-. :g the structure arger resolving lOQ-IOGO times ds on a small .etion methods, f atoms within JNAN. 1961). lensiona of the tly the diiTrao* \ Pio. t. Schenst.c C.'e;rsm of microirulywr. Example o' -r. electron imaje rij. <a Example o* a X-ray im;;* Fij, O Example o' ir.s rccordm; of the pulse monitor Ftp. 3. *. 7. % DOW 06880  ISO J. Stvmpiiius and ?. S. Mrrix , emitted by the specimen's surface, are trapped in the phosphor of a photomultiplier rube. This results in a signal, which, after amplification, is made visible in a display rube forming the electron image, see rig. I. When struck by the beam of electrons emitted by the electron gun, the specimen will emit r.ot only secondary electrons but also X-ray fluorescence radiation. The wavelength of this radiation is characteristic for the elements which emit the radiation while the radiation intensity is related to the concentration of these elements. By spectroscopic analysis of the radiation emitted, it is possible to obtain a qualitative and semiquantitative composition of the selected part of the specimen (COSSUTT, 1966). EXPERIMENTAL RESULTS AND THEIR DISCUSSION Figure 2 shows a typical asbestos body as seen in the light microscope. The identification of the kernel of the asbestos bodies oy electron diffraction was hampered by the amorphous protein coat and was attempted by means of the X-ray microanaiyzer. The first results gave the impression that the kernel consists mainly of iron and oxygen, while traces of silicon, phosphorous and calcium were also found. At this point of the study it was deemed useful to continue study of the structure of the kernel of the asbestos bodies by means of electron diffraction. The asbestos bodies were isolated by the use of a micromanipulator and treated with a mixture of KCl and H,0, in order to strip, at least, partly the coat from the kernel. Fig. 3. During this stripping operation, it became clear that the coat is not homogeneous but consists of layers, varying in density which are deposited around the original fibre. The section seen as the kernel of the asbestos body, when using a light microscope, often consists of the kernel plus the first layers of the coating. The actual kernel is often thinner than originally presumed (a few tenths of a micron). As the resolving power of the X-ray microanaiyzer is of the order of 1 fiin, the X-ray fluorescence radiation must principally originate from the high iron content of the coat and fora very minor part from the asbestos fibre. The effect of the thickness of the coat is shown in Fig. 4, which illustrates an asbestes body for which the composition has been studied at sections where the coat varies in thickness. Tiie results of this study arc shown in Figs. 5, 6 and 7. Figure 3 gives the X-ray image of the same asbestos body produced by the iron fluorescence radiation, giving a qualitative picture of the distribution of the iron. Figures 6 and 7 give more accurate quantitative results. So in Fig. 6a the vertical axis gives an indication of Che concentration of iron along the location on line a from Fig. 4, and Fig. 7a shows similar data for silicon. Figures 6b ar.u 7b provide the same information as 6a and 7a, but now for line b of Fig. 4. Figures 6c and 7c provide this information for line c of Fig. 4. Similar lines have been established for the elements calcium, phosphorous, oxygen and magnesium. Electron diffraction studies carried out on practically stripped asbestos bodies showed that the kernel consists of an amphibolc type of asbestos. 2y this method it was possible to identify the core of eight asbestos bodies. In addition, investigation of the original sample, sent to 7X0, was found to contain uneoated asbestos fibers. Out of 27 flares investigated by electron diffraction 17 appeared to belong to the serpentine variety chrysotile and 10 were classified as belonging to the amphibolo type (probably variety crocidolite). v S ' ; j ] ' 1 i ' > j ! j ; ! ! .i j ; ; t STOOI1598 Flo. L Alton r to. J. An cieeue: DO^ ST00N599 / Asbestos bodies cr.d mesothelioma 291 Although approximately j of the asbestos fibres collected from the original sample could be classified as being of the chrysotilc type, while the rest were amphibole, it is noteworthy that all the cores of the asbestos bodies which have been inves* tigated consist of an amphibolc type of asbestos. Various explanations for this phenomenon can be offered, for instance: 1. since asbestos fibres of the amphibole type are generally thicker than those of other types the asbestos bodies are more noticeable and are therefore easier to isolate; 2. when both amphibole and chrysotile types of asbestos are present simultaneously in the lungs the amphibole type of asbestos is more likely to be used as a kernel for asbestos bodies. It has been reported (Berkley, 1967) that the proportions of iron, silicon, oxygen and magnesium of the core of asbestos bodies, as determined with an X-ray micro* analyzer, do not correspond to any known type of asbestos. Berkley (1967) suggested that this is due to attack of the asbestos in the pleura where atoms of silicoa and magnesium are displaced by iron atoms. The investigations described above show that the lack of correspondence can be explained by the varying thickness of the protein coating containing iron, which is deposited on the asbestos fibre. Thii is illustrated by Fig. 7a, band e and b which show the increase of the silicon concen tration due to the decrease of the iron containing protein coat of the asbestos fibre. Proof that the increase of the silicon concentration corresponds to in successive traverses, e to c a decrease in the thickness of the coating is evident in Fig. 4. The iron eoncentration, on the other hand, decreases with decreasing thickness of the coating as shown in Fig. 6a, b and c due to the fact that the iron content of the protein coat is higher than the iron content of the asbestos. Apart from this, no indication of contamination or attack of the asbestos fibres forming the kernels of the asbestos bodies has been found. Concerning the existence of pseudo-asbestos bodies, it is to be noted that in all cases investigated by TNO, the core of the supposed pseudo-asbestos bodies proved to consist of asbestos. While it is premature to draw any definite conclusions on account of the limited number of determinations which have been carried out to date, definite doubt regarding the existence of pseudo-asbestos bodies appears justified. From experience acquired during the tests, the impression is gained that electron diffraction, supported by the X-ray microanalyzer, is the only method which is able to eliminate the influence of the coaling or residuals of the coating on the analysis of the core. Finally, it should be remembered that the role of asbestos bodies in the genesis of 'mesothelioma has not been dealt with. It is believed that experiments with animals are necessary to clarify this. CONCLUSIONS 1. Though there had never been great asbestos exposure in the mesothelioma cases in Flushing, the amphiboles found in the asbestos bodies may have caused the tumour. 2. So far, there have been no cases of mesothelioma ia the small community living ia the immediate vicinity of the yard at Flushing. It should be realised that there may bo other factors functioning as oo-carrinogeos. The iron oxides should be DOW 0688? t i 1 i I I . i: i !` l t i l*.. . i. -i.. f. 292 3. Stwthius and ?. 3. Mcrm taken into account since a!! mesothelioma eases from the yard had had heavy ex posure to them. 3. It should be realised that the ever growing amount of asbestos in the human community, which cannot be neutralised in any way, may lead to a steep rise in mesothelioma. The amphiboles, in particular, may be a special risk. 4. There are strong indications that electron diffraction, supported by investiga tions with the X-ray microanalyzer, is the best way for examining the cores of asbestos bodies. 3. The existence of pseudo-asbestos bodies must be considered extremely doubtful; it is believed that the analytical method used to identify them was inadequate. 6. It is believed that the unusual composition of the cores of asbestos bodies, found by chemical analysis and with the X-ray microanalyzer, is caused by the , protein coating which contains a high percentage of iron. 7. Research on the part played by the inhalation of amphiboles and iron oxides in the genesis of mesothelioma must be carried out with animals. AcA*wfr<fnr*rr--Figures 3-7 wen made by A. P. Von Rouxmu. and H. B. Zsaotnc of the ` Metal Research Institute TNO. The isolation and stripping of asbestos bodies was carried out at the Microbiological Laboratory of Prof. Wikdn, Technical University, Delft by Misa Vos and 3. van oik Toouc. * , j r i REFERENCES i Anjilvsu L. and TiiuiLitCK, W. M. (1966) The incidence of asbestos bodies in the lungs at random necropsies in Montreal. Can. mtd. Au. J. yS, 1179. Atbeitom. The fntumaeoniotit (1967). Med. Series no. 12, Ind. Hyg. Fndn. of America, 4400 Fifth Avenue. Pittsburgh (Pa). Suciiimo, R. (1946) Electron Dlffroetian Methuen's Monographs on Physical Subjects, Methuen, London. Birkuy, C. (1967) 7/A lai. Con/. Medical and Biological Engineering Stockholm (August) No. 423. Calna, Dm Tot-tin, R. S. and Gaoss, med. Alt. 192. 371. 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C., S; nj-*""* iaN` 0 0 9 1 I001S DOU 06883 i 'eavy tx- e human ? hse in nvejtigacores of oubtful; bodies, by the n oxides of the tbenitqr I I [ | r i i i* i Asbaio: bodiii lsA tnesoths^orr.* S3 Stuxorr, I. J.. 5aoct. X. A.. Bads*. M. E-. C.uao, J. and Cirrus Hammons, E. (1937) A.ie:o and ncopUum.v Editorial Am. J. Med. 42, 7. Sttwaat. M. (19:9) Br. med.J. 0, 31S. Thomson, 1. C. (1963) Asbestos u modem urban hasard, S. Afr. med. J. 37,77. Thomson, J. G,, Path. F. C and Gxavxs, V/. M. (19M) Aibatos u sn urban sir ccr.tsnuiunt. Ardu. fatk. 11,453. Uuman, F. (19(1) EncykhfiHt dtr TeehnUthsn C.emU VoL 2/1, p. $64. Urban vad Scfcwirtttv best. Berlin. Yi.-cun. Wacno. J. C, Suoes. C. A. and Mascmato, F. (15C0) DiAso plain! mesothelioma ani sibcstoe exposure in North Western Cape ProL-.s, > J. ted. Med. 17,260, > nodosa *00 Fifth teihvea. No. 423. '.Vi 4^4 10.4IS. 'MtU Of J4. its, ubi^ Juttriel lowing .*, K. J.Am. t L i i t iii S T 0 0 I1601 t i ,i'. i . i! i f Ii l | i I [ DOUI 06884