Document ppymMmv6mv8pJpODGKvB2e5o7

General Headquarters January 28, 1969 C. B. Burnett P. M. rin^ornp Bert Goss, H & K H. M. Jackson J. B. Jobe K. V. Lindell, Asbestos A. B. Marchant F. L. Pundsack, finderne W. P. Raines Ivan Sabourin, Montreal r t. cKo^v] w2T# Findcrr.~ A. C. Smith, Finderne R. R. Standell M. M. Swetonic Carl Thompson, Hill & Knowlton W. L. Van Derbeek, Finderne Dr. G. W. Wright, Cleveland Attached is the Eleventh Annual Report of the Asbestosis Research Council for the twelve months beginning October 1, 1967. Enc. C f/ j Solon, Jr. SH/HS ASBESTOSIS RESEARCH# COUNCIL ELEVENTH AM!UAL REPORT FOR THE TWELVE MONTHS BEGINNING 1st OCTOBER. 1967 1. INTRODUCTION The Asbestosis Research council was established on the 1st October, 1957* This report details the activities sponsored by the Council during the eleventh year of its opcrdtlon* 2. CONSTITUTION The Constitution was revised in August 1965 to fivld of activities to asbestos operations other than textile and to provide for the admission of Associate Members as well as Full Members. 3. MEMBERSHIP The Membership of the Council during the year was as follows Pull Members B.B.A. Croup Limited. The Cape Asbestos Company Limited. Turner A Newall Limited. Home Associate Members The Atlas Stone Company Limited. Bell's Asbestos and Engineering Limited. T.B. Ford Limited. (In place of Birfield Limited). Richard Klinger Limited. The Universal Asbestos Manufacturing Company Limited oeased to be an Associate Member on becoming part of the Cape Asbestos Company Limited. Overseas Associate Members James Hard!a A Coy. Pty. Ltd. Johns-Manville Corporation. The Quebeo Asbestos Mining Association. Griqualand Exploration A Finance Co. Ltd. /oont'd... nnni u L` u O L 5 AC 150 -2 - A. COMMITTKHS The affair.; of the Council were administered by three Committees, the Kasvibomont Committee, the Research Committee and the Dust Control Committee. The membership of these committees during the year was (a) Management Committee Chairman ! t R.H. Dent - The Cape Asbestos Co. Ltd. nr. R. Gaze - The Cape Asbestos Co. Ltd. Ur. C.M. Fenton - B.B.A. Group Ltd, Dr. C.G. Addingley - B.B.A. Group Ltd. Mr. J Waddell - Turner & Newall Ltd. Mr. R.H. Wilson - Turner & Newall Ltd, Secretary : Dr. S. Holmes - Tui-nr A Newall Ltd. Mr, J. Waddell resigned in May 1968, his place being taken by ur. n.',y. Hills. Management Committee meetings were held as follows :- Uxbridge London Manchester Rochdale London London 27th October, IS67 5th December, 1967 6th March, 1968 8th May, 1968 *kt July, 1968 26th August, 1963 (b) Research Cogpitta3 Chairman Secretary Mr. R.A. Wells Dr . a. v. i.einsonn " Dr. C.G. Addingley Dr. W.H.A. BererleyDr. A.A. Hodgson Dr. W,J, Smither Dr. S. Holmes Turner A Newall Ltd. Turner A Hawaii Ltd. B.B.A. Group Ltd. B.BcA. Group Ltd, The Cape Asbestos Co. Ltd. The Cape Asbestos Co. Ltd. Turner A Newall Ltd. Research Meetings were held as follows Rochdale Cardiff Reading - 2/iri. Januaxy, 1968 - 21/22nd May, 1968 - 17/l8th September, 1968 In November, 1967, the Research Committee held a ono-day scientific meeting at Cleckheaton on 'The Early Diagnosis of Asbestosis'. The Pneumoconiosis Medical Panel was well represented, along with research workers in this field. /oont'd... ( c) P-uU c - 3- Ch.iiju-'ui : Mr. J.w. McF_rl.ario Mr. M. Roy ~ Mr. T.iV. Ardors c;i Mr. P.K. Rugge Mr. R.H. Wilson Mr. ff.P. Ba.-:blin Sccretaiy : Dr. S. Holues The Capo Asbestos Co. Ltd - B.P.A. Croup Ltd. - The Cape Asbestos Co. Ltd - Turner & Hewall Ltd. - Turner & Newell Ltd. - Turner & Newall Ltd. - Turner & Newall Ltd. This --,-- _1 ^ L e v.is ru-^^..,,.j.tuted in July, 1 9o3, as the 'Enviro-'jnor.t.tl Ec.r.tr'1 Co^aitt.c-^., under the Chair-nans hip of Mr, \.A. Cross. It held its first netting on 22n4 August, 1?68. Bust Co:.t: ol C tec uec-t irgs were held as follors s- Roohaale Hebd-ii Bridge - 2'+ th January, - 5th June, 1968 The firuinoes cf the Council have continued to ho administered through accounts operated hy the Rochdale Branch of the District Bank. (h) Budget and Expenditure Council Budget Expenditure 23,500 19,130 B.AIB... tuir. Ginx-ut _ijTgV3TED__B0DIES Contact has been maintained with H.M. factory Inspectorate and the Panel convened by the Senior Medical Inspector cf Factories, on which two of the Council's Medical Officers served, has published its Report entitled 'Problems arising froa the use of Asbestos'. Liaison has continued with the Pneumoconiosis Research Unit of the Medical Research Council. The opportunity was taken during the meeting of the Research Committee at Cardiff in May to have a joint one-day aoeting with the Unit to discuss common problems. Arrangements have been put in hand to organise a joint ARC/PRU Conference in April, 1970 on 'The Tissue Reaction of Asbestos*. /cont'd I _I The Suh-Cejuni tt -a; r-ci up by the Hygiene C Mimi4,tee of the Britj Occupa* local Hygiene Society, on whi<h members of the Council served, published a Report in April 1568, entitled 'Hygieno Standards for Chrysotile Asbost:-: Duatr. Liaison has also continued with the U.S. Public Health Service and with tho Air Hygiene Committee cf the Asbestcs Textile Institute. 7. RESEARCH PROGRAMS The research work of th* Council was further expanded during the year by Grants to Dr. Margaret Turnpr-^ervi-'1'' :f the Lonij.i Iloapn.ol or u.'-reasea of the Chest and Dr. Margaret Swinkvrne of St. Jaoss' Hospital Leeds. A summary of the year's work is given below. Puller reports appear in Appendices 1 to 5. (i) The long term animal experiments involving the inhalation of the four main types of asbestos have been completed during the year, but macy of the sections are still to 0? examined. The studies on the mechanism of asbestos tody formation have also been completed. Collaboration with the Institiit fiir Lurehygiene in Du33el.de: f has continued. (ii) The collection of biopsy material ft-oa suspected oases of human mesothelioma has continued and the production of mesothelial tumours in animals has been further studied. Vork on the pathogenicity of minerals ether than ashe StCC h3 been started. Collaboration has continued with Dr. Gross cf the U.S. Industrial hygiene Foundation in Pittsburgh. (ill) Preliminary work on the effect of asbestos on lysosomal oell systems terminated in June, 1968. (iv) Vork on the surface properties of asbestos has continued. (v) An immunological study has been started but only 1 preliminary results are yet available. (vi) Animal experiments on the ingestion of asbestos have commenced and it is hoped to have some results in the next I twelve months. /cont'di 5 While the Royco Automatic Particle Counter has continued to bo used as a routine r.-T.itoring instrument, the fibre count by nenbr.irto filter has r< rr.aincd the standard method in the industry. The method has been published by the Council as its Technical note No. 1. Techniques for assessing the asbestos content in other than industrial environments have been further explored. Interest has been shown in this subject by a number of Governs-.ert Departments ard a meeting of those involved was convened by the Ministry of Technology in liay, 1968. Representatives cf the Council were present. During the year, the Council has carried out a survey to determine the level of asbestos dust in completed buildings of various types in which asbestos products have been incorporated in their construction. & report has been prepare! for puoj.icati.ot-. 9. DUST CONTROL During the first part of the year, the Dust Control Committee continued to work on various problems affecting the manufacturing and applications side of the industry. In July, 1968, however, this Committee was reconstituted with the title of 'Environmental Control Committee' and with wider terms of reference to enable it to deal with all relevant natters likely to affect the industry and its customers under the New Asbestos Regulations. 10. THE NEW ASBESTOS REGULATIONS In April, 1y6B, representatives of the Council were called to a meeting at the Department of Employment and Productivity to discuss the Council's comments on the preliminary draft of the New Regulations. It was learnt that the Council's suggestions were likely to he given consideration in framing the Statutory Draft, in particular the replacement of the 'no dust* concept hy a more practical approach to the problem. The Statutory Draft was published in August, 1968, Bd the Council again felt obliged to make a number of comments, which are still under discussion. 11. CODES OP PRACTICE During the yeer the Council issued its fourth Code of Practice -- 'Recommended Code of Practice for Handling Consignments of Asbestos Fibre in British Ports'. /cont'd... AC ISO I'i continue! s;. ! '1' , Jj. all Cedes or Practice has "The Jlcchani.-.m of >1 r;:n * ion of Asbestes Bodies" S.K. Both .:; :;;i P.P. Holt, J. Path, and Bact. Vol. 96, Ho. 2, p. 443. "Interaction of Poly-Z-Viryl Pyridine l-Oxide and Poly-b-Vinyl Pyridine Oxide nith tionocilicic Acid" P.P. Holt and P.P. Nasrallah, J. Chea. Soc. 1968, p.400. The nuri. done by the Herb or Companies in this field has ccr.tirjci to V. j reviewed by the Research Committee. In Ii'ove:sb-. r, If o?, Mr. x'addeil, Dr. Gaze, Dr- Knox, Dr. Srither, Dr. Beattie, Dr. Davis and Dr. Holmes attended the Second Antirun Conference organised by the Quebec Asbestos Mir.ir..~ Assccitticn. Dr. Addir.flcy, Dr. Knox, Dr. Smither, Dr. Davis, Dr. Holt, Dr. Leninsohn, Mr . Hunt and Dr. Holies attended the International Conference on the Biological Effects of Asbestos held in Dresden m April, 1968. GIDInPbUC Dr. Knox has continued as Medical Consultant to the Council and has attended the meetings of the Management Committee and the Research Committee. Dr. Beattie has continued as Research Consultant and has attended the meetings of the Research Committee, APi'i'imx i Report, on H^r^arrli a I tl.c University of Rc'.d;nr - Dr. Holt During tins yen r..i:-t of the lorg tern, uxperji.ients started 2 to 3 yearj ago, in which guinea pigi and rats inhaled four types of asbestos, have been completed. This has required a heavy load of tissue processing and cutting to provide about 3,000 stained sections. It has been impossible to examine many of these sections while the experimental work was proceeding and consequently few final results have been reported. There is non available, however, a library of sections in which the effects ^n the lung.. _;.i lymph glands of reasonably small doses of inhaled anosite, anthophyllite, ch"ysotile and crocidolitc can be studied. There is also a series of slides in which (j'cir.ea pigs arc c:spared '"ifh rat; that have inhaled asbestos. These are unique. The following tentative conclusions need to be confined. The asbestos dust is first deposited in the bronchioles, the longest fit;co (up to 7?/- - _) '' tkr torainal bronchioles only. Remarkably, some fibres subsequently appear to move into the alveoli which is contrary to what would be expected. No histological difference has yet been observed between the effects of the four types of asbestos but a few pleural adhesions were present in animals that had received axositc ar.i crooidolite but none in those that received anthophyllite, chrysotile or glass fibre. Ho clear morphological difference has been observed between the asbestos bodies produced on the fovr types of asbestos; those produced by glass fibre are similar e.-.cept that, since they form round single fibres rather than fibre bundles, they are usually smaller. In a search of other organs for evidence of transport of asbestos from the respiratory system in a guinea pig, so far one perfectly formed asbestos body has been found in the thyroid gland. The studies on the ueoiiunism by wnxen asbestos bodies are produced have now been completed. Tho initial effect of the fibre in the lung in the production of haemorrhage and the resulting iron-containing compounds from the haemoglobin in the red cells are taken up by dust cells and deposited on an asbestos fibre in the same cell. The production of an asbestos body does not therefore depend on the chemical nature of the fibre and we have produced bodies from mica fibres and very fine glass fibres. This last experiment is being extended and some guinea pigs have been made to inhale glass fibre and others glass powder of the same chemical composition. In experiment has been concluded which was set up to investigate whether the progress of pneumoconiosis due to asbestos could be followed in animals by chemically estimating the collagen formed in the damaged lung. The results are disappointing; the variation between animals is at least as great as the variation caused by small dosea of asbestos. /cont'd... bn n rt t> i< u C tTi Now that the fundamental .vorX with animals is well established attention is being turned to the methods of modifying the pathological effects of asbestos. Studies are continuing on the possible use of polymeric substance such as poly-2-vinylpyridine 1-oxide, which lias proved effective in silicosis in animals and on whether this polymer can alter t'no rate of fragmentation of asbestos bodies. The possible coating of the asbestos with an adsorbed monolayer, either to modify its effects or to prevent its being retained in the lung, is also being investigated. The initial studies on adsorption are now vrell under wTy :,ad early results will be reported during next year. T APr:-r:piy. Report on R-,: v -ch .t the U- 1 v-rsit , of Cavhiid -i - Dr. Pavla Hu:::1.n 11 ;o\:.? 1 c .-t Rier o.ir s Throughout t.'se year the collection of biopsy materiel from suspc-ofed c:.u; of human mesothelioma has continued, although during the last twelve months only foar cases wore reported in time to collect too r.at f""'!, Of these care; ~.\o has since been confirced as a mesothelioma at autopsy, two were varieties of bronchial carcinoma, and in one case the suspected tumour mass was found to be anfla:r~.atorv and n^t neoolastic. One of the two bronchial carcinoma cases was especially interesting as before the patient died it was possible to diagnose the tumour as an alveolar cell carcinoma from its cell fire structure. Autopsy confirmed th; + 'r was indeed a peripheral lung tumour. This indicates that when sufficient knowledge is available, electron microscopy studies nay be useful in mesothelioma diagnosis. y.esethvlic.ta production in animals These experimentc have continued this year vith both nice and guinea pice. Curing this period 16 guinea pigs have died and 28 mice. Despite the fact that 13 of the guinea pigs had survived over two years from the time of injection and 11 of the mice had survived more than one year, only one pleural tumour was found. This was in a mouse that had been injected with chrysotile 14 months before death. The histological pattern in this case wao not typical of mesotheliomas from ether species but mouse mesotheliomas are not yet well documented and more tumours are needed tc be siuo of the diagnosis. Although inly one possible mesothelioma has been found this year, three guinea pigs developed bronchial carcinomas, one a squamous cell carcinoma of the skin and one a spindle cell sarcoma. In the mice two subcutaneous sarcomas were produced. The guinea pig spindle cell sarcoma was definitely caused by crocidolite as part of the injected material had failed to enter the pleural cavity and was found in oontact with the tumour. The other animal tumours could not definitely be associated with the asbestos injeotion, but the incidence of seven spontaneous tumours out of 42 deaths is high for an animal population, and the possibility must be considered that some of these tumours resulted from the asbestos injection even though they developed in sites far removed from the dust. Apart from definite tumours two interesting facts have emerged from these experiments. In the guinea pigs tho intrapleural dust Ip-.in"? have been found uo calcify after about eighteen months to prod"cr typ.-ic.nl /cont'd j ; ! j i A MTHM)!* 7 (c.n'.'d) calcific-l pleural plague:., hi: lolcgically very- similar to those fouuJ in human case:.. In the nice the pleural fibrosis had often developed to r dc-grt- rhere the jOenrol cavity was completely full and the lunga `ucuoed by L ie .e: o/ f..brou tif-auc. Tho nacroscoplo picture was exactly that of a rosothelioua, but histological examination showed r.o signs of poop] isia. It would appear that this massive fibrosis is caused by o turnoscT of dust. V/hen the initial dust granuloma ages the macrophages and gaint cells die and are replaced by fibrous tissue. The asbestos dust is left behind among the collagen fibrils and is rephagenytesed by a new generation of macrophages that actively penetrate the films tissue to pick up the dust. This turnover process appears to continue as long as dust is present and very large masses of fibrous tissue eventually resulted. Ineiu is one type 01 fibrous mesothelioma that pathologists find often difficult to distinguish from normal fibrous tissue. These fibrous masses are in fact only considered tunours because they grow to a very large size. Proa the Bouse evidence it is possible that they may not be tumours but normal fibrous tissue constantly stimulated to new fciowin by a. relatively iniestructablo content of asbestos dust. Experiment to test the cothorcnlcity of minerals other than asbestos During the last twelve months the following minerals have been tested by intra-pleurul injection in mice Talc, serpentine, brucite, magnetite, pyroxene, olivine, forstcrite and chlorite. So far, all these minerals have failed to produce lesions other than the normal foreign body reactions. The results cf injection experiments with fine glass fibre (dia. 0.05>u) end calcium silicate are still under review. follow-up experiments involving Inhalation on all those materials are planned. Experiments with P2Qi During the first part of this year experiments Continued which were designed to test the effect of P2W*. on the development of asbestos lesions in guinea pig tissue. With the chrysotile sample used, no difference could be found between animals treated with dust P2Q!*. and those that had received dust only. ?or this reason, the experiments were terminated in llaroh. During September, however, some experiments were started using samples of synthetic chrysotile injected intraperitoneally into mice. This dust has proved much more toxic than normal asbestos, and it may be worth repeating the P2C4 experiments with this dust. Experiments to determine the chemical processes of asbestos body formation Two studies are at present in progress in this field. These involve the electron microscope examination of very old calcifying /cont'd... nI Mo jtiti Qt APFXUDir. 2 (cont'd) ashes'os Ifjioi.s and very young lesions in the-guinea pic pleural cavity. IJnr::il asbestos bodies are produced intracellulerly end perhaps ar. fev as one in one thousand fibres of dust ever become coated. It has been found, however, that in old calcifying lesions, which are acellular and where the dust is now lying fVoe among the collagen fibrils, all asbestos fibres become coated with a layer of material about as thick as the normal asbestos body coating. This coating is much less dense than the 'ferritin* of normal asbestos bodies although some 'ferritin* granules nay be present among the other coating material. From a study :f the substances known to occur in calcifying tissues it appears most likely that this coating material is a mucoprotcin or mucopolysaccharide. Since colloidal i r ** Trll s+ain fYjt* 5.3 9ffccti75 tiic iron selectively impregnates the mucin, it begins to appear likely that asbestos body formation may be a two stage process, an initial coating of nucoprotein or mucoploysaccharide being followed by the impregnation of this material with ' ferritin'. The density of ' ferri*dr' :r. 1 '-ierios bodies night be due to its high content in living granulation tissue, and the low content in the calcifying tissue bodies nay be due to lack of 'ferritin* in these dead avascular area. An examination of very early asbestos lesions is new in progress and already some dust fibres have been found in giant cells coated with low density material containing only a few granules of 'ferritin'. nnni i i a r> uuu0 C 1 AC 150 AiVi'.'in/ i t cn Reve~.r,h the ftr..i . .us Laboratory - Dr, Barrett I"?1'- _:~ -1r .i, Jurn 1 9o^) iVork on f'aorouh t..'; It haa been four.5 prosit]? to rajn> ain noose peritoneal caci'eph-g 5 f" r six dayj in Medium 199 (Burroughs well cone) 5ip::li:>,r..3 th 'C0 ur:u .'Vlc-d *.a".f Etrjn in an atmosphere of 5'- fOg/M-V uir, u'Vt;-.i.p5, but a st.-ij.uus difficulty arose in that ti.n available, assay tec briquet; proved not to be sufficiently sensitive to detect the release and synthesis of enzymes by the maintained. A sore sensitive method lias however, only recently bi vn devs-leyi and this s:.c :ld prove invaluable in future experiments of this natur e. 7h-- : v._ Lati _ the- ft ability of Lusczones A rat liver .van homogenisei in 0.25 U sucrose, end a mitoehondriallysosos.el preparation was obtained by differential centrifugation. This os suitable- diluted and intubated at 37, either alone or with a rothar dense suspension ('.0 rf/rl) of finely uillcd chrysotile asbestos (suppliei by Dr. P.?. Holt). Over a period of three hours, the mixtures were gently agitated and samples nere removed periodically and centrifuged. Determination of the enzyme activity in the supernatant and sedimented fractions gave a measure of the extent to which the limiting membranes of the lysosomes had broken down, under each treatment to release the enzymes in a tree, soluble fora. Workers haw sheen t:-.3t quartz can act by rupturing lysosomal membranes and it seem.-d likely that asbestos would have a similar effect, in view nf its iiae..oIy tic activity, wmch was comparable with that of silica, but no such effect was detected; parallel release of acid proteinase was obtained in suspensions with or without asbestos. In view of a recent German report or the action of asbestos on lysosomes in vitro further experiments of this type night be justified. The Collular Consequences cf Phagocytosis Lysosomc-s form the digestive system of cells, and in maxy ways this is comparable with that of higher animals. When a macrophage engulfs a bacterium, it is enclosed in a digestive vacuole, or phagosome, the contents of which are acidified. The lysoaomal enzymes, which are active under acid conditions, are then secreted into the vacuole and the bacterium is digested. It is known that the biosynthesis of the lysosomal enzymes is stimulated by the process of phagocytosis in macrophages (and the same nay well apply to the macrophages that take up asbestos, if they survive). It is r.ot /cont'd... :'j.*'T-V?S' mw1 n n n- uuu iii C Jc AC ISO AmiiPlX 3 (rout'd) thought that ti.i- is scl..lj a ch.'.i uotei istic cf phagocytic leucocytes since \uvioua tissue cell t.ypus cun show phagocytosis and a lysosomal response, in tissue culture. Ccucrully the lysosomal digestive ciir.yr.ii'r. produced in rcu.punro to the phagocytosis arc not confined to the intcri-cr of the colls, but arc released into the cultuic medium, and in organ cultures of c. ilagionous bone rudiments the result is an extensive digestion of the extracellular matrix strongly reminiscent of that seen in rheumatoid arthritis. It is felt that excessive lysosomal activity of this kind may well be involved in the pathology of rheumatoid arthritis ani certain other conditions, and investigations have been dv..^ o.i l,.* way in which endocytosis (a general term including piuocytosis and phagocytosis) stimulates the synthesis and release of the lysusosmal enzymes. The biological system used is one in which chick embryonic limb bane rudiments are cultered in a synthetic medium to which sucroso has been added. Surprisingly, the cells are unable to metabolise sucraae, end it causes the formation of persistant large digestive , jo. ` tut there is no cell mortality and coll division is scarcely inhibited. There is, however, a dramatic increased in the release of lysosomal enzymes. The radiochemical mioroassay is designed to follow the time-course of the new synthesis with precision, and an inhibitor of protein synthesis, cycloheximidc, is being used in an attempt to decide what proportion of the enzyme release represents newly-fornod, as opposed to pre-existing molecules. Further work has led to the preparation of a pure rabbit anti chicken acid proteinase antiserum with which it is hoped to isolate minute amounts of the enzyme synthesised in culture in the presence of radioactive tracers, as the immunoprecipitate. This would allow changes to be followed in the specific activity of the released enzyao which could give valuable insight into the mechanism of t-h Stimulated X'vauase. nnni 1r u u O AC ISO APPENDIX If Report on Rorvarch at the University of L^edr. -- Dr. Grimshaw During; * he last twelve months period the research programme has heon directed mainly to studying the release phenomena of magnesium and silicon from chrysotile under a variety of conditions. A raw Canadian fibre was selected for detailod analysis, but other samples have been shown to possess similar characteristics* Both magnesium and silicon can be extracted from raw fibre under most pH conditions. The amounts were greater in acid solutions but the ratio of MgO : Si02 in solution bore no relationship to the stochiometric composition of the parent minuxal. Once the fibre had been ground, the amounts of cation release increased enormously and to a far greater extent than would be expected from simple surface area considerations. Chrysotile which h".d k-.-m--ivind for a few hours still possessed a typical fibrous habit when examined under the microscope, but it was possible to extract virtually all its structural magnesium. Comminution processes also caused marked changes in X-ray, infra-red and differential thermal patterns. Perhaps the most significant observation of the release phenomenon in treated chrysotile is the fact that the absorption capacity of the mineral was increased considerably. Rot only was water absorbed but also cations other than magnesium and many organic compounds and complexes. Stearic acid and some amino-acids were absorbed and the mechanism involved chemical as well as physical phenomena. It has been shown by infra-red studies that the characteristic spectra of certain organic groups changes markedly T7h?r* --wCOi't'SU OistfW Um* treated cnrysotile fibres. ii r r v i* u L- ** AC SO 0 In cullubci at ion v;ith Dr. Pnrkes of the Pneumoconiosis I't dical Panel, pnticir.s referred to the Panel for assessment have been examined in person aid it is hoped that this special series will foru the basis cf a long-term follow-up study. In addition blood sera supplied by co-operating chest clinics and industry have also been or.-mined. Included in the study so far hare been 33 patients ana 11b blood sera saauaes. factors H A - r' l ~ v -* .'* - - ruratoid factors have been studied. ;^ - t. .h.'iiqui., iCy I'-.r. found to be A.U.F. positive, against an expected figure of 3? in a 'normal* population, Asss: "i.r.g rheumatoid factor by the differential agglutination tit re t e.-hriep. i (D.'V), the percentage Did' positive was 37, against an expected lacs then iy in a 'normal' population. Using Latex r: . L'.'.to ^1-. ... pti.eiitagu positive was }'). Antinuclear factors rkeunatoid factors have therefore been demonstrate! more frequently than expected by chance in patients with asbestosis. Purthers ore, th-_ incidence of these antibodies is remarkably similar to findings in idiopathic fibrosing alveolitis. The next study is to analyse the clinical, radiographic and physiological features corrtl'-i ed v/it h ir.vunolcgical re-activity. A scare;; for lung reactive antibody lias been undertaken in 2U patient-> using the antigloculin consumption test (AGCT). It appears that antilung reactive antibodies are present only in low titre and are unlikely to be an important immunological finding in asbestosis. Irruncfluorescent studies have been carried out on tnres aabooivllc lungs. There was no evidence of antibody nor complement fixed to any structure surrounding asbestos bodies within the lung. Gene:r:-.l Conclusion Circulating r.cn-organ specific tissue antibodies have been found in patients with asbestosis. Moreover the incidence of these as similar to that found in fibrosing alveolitis. These findings suggest that a similar immunological stimulus occurs during the development of both these lung diseases. Whether the immunological response is damaging or protective is unknown. An attest to get further evidence for or against a pathogenetic role of these antibodies (or some immunological reaction occurring pari passu with them) will now be sought through a study of these antibodies in different stages of evolution of the disorder, using clinical, radiographic and physiological data as the yardsticks to assess the extent and severity of the disease. 3 AC 150 KltTenth annual rtabort 1st October. 1967 30th ,,apteaber, 1968. jw. 7,1.1 ASBESTOS1S RESEARCH COUNCIL //,// //, Mr ippgcog s Report on Research at the University of Caabrldaa - Dr. Pavia Publications s- Tork on Ferruginous bodies, end calcification in esbestos lesions was ooapletea thi* ym-. Some espeots of this work were incorporated into two papers* These were:- (e) The fir* structure of 'Ferruginous bodies' produced expariaautally in Guinea pigs fron einereis other than asbestos. This has been accepted for publication la the 'Irohlvae of Pathology'. (b) Asbestos dust as a mielection centre la the oalciflcatine of old fibrous tissue lesions, and the posaibla association of this prooess to the fOmatioa of asbestos bodies* This has been accepted far publication in 'faparieental and Molecular Pathology*. , Research Topics (a) The electron-microscope exsal nation of hunan nesothelionas During the year, three biopsy spoelnoas earn obtained, but none of these was finally ooafiraed as a aesotheliona* Work on this field is still United by lack of aatedal and has not adwanoed during the currant year. (b) Production of Mssothellonas in Anlaala ualae aabeatos duet These experinants have oontiaued with both Oulaoa pigs and alee. Originally staples of chrysotila and orodioolite dost ears supplied by Dr. Kolt, but now the D.Z.C.C. World Bonk eanplee are need. Be nesothelionas have been Obtained la fiwlnse figs although Mao ontnalo hare no* survived for non than thraa years after dost injection. Two Aeflnito nesothelionas have, however, been found in aloe and slaotroa-oieroseope examination is now in pragmas, linos marly 100 aioo have ao far baea used In these studies, and died wltboed producing tunours, a total of two maothslloms la still a rw*y anil poroentage and la ao way ooapams with the high figures produced ly W*gn**. (o) Bneriaente on the pathorenlcltv of *-- *1* These tests using intrapleural injection have eontinued throughwt the eurrent year, sad it la now posaibla to divide the teat eanplee late three categories. -2- These are 1. Ulnarala which produoe an Initial foreign body reaction, but which diaaol7e with nr without toxio effect*. With dla3olution the foreign oody reaction uoLines and nay completly resolve. In this class are :- Bruoite, ?Orsterite (rr-odueed 'ey heating I'hrysotlls), calcium slllouta, w--1 probably synthetic chrysotlle. 2. Minerals which produoe a foreign body reaotion that results ia the formation of large granulomas which enclose the dust. These granulomas lie loose in the pleural cavity, do not fora aibesi.^j, o-- 0.^0or t.o oause the "<' no dlsoomfort at all. The minerals In this class do not appear soluble and the granulomas do non decrease in sixe with age. TCbrosis occurs within the granulomas, but not elsewhere la the plaural cavity. In this class ore Tale, Serpentine, Magnetite, Pyroxene, Olivine, Chlorite, Chrcnite and glass fibre that has been - machine ground. 3. Minerals whocn produce large spreading granulomas. These lesions adhere firmly to the chest contents.and say oauss massive adhesions between the lung lobes, the diaphragm and th* ohast wall. These granulomas are often replaced by fibrous tissue, and in extreme rases the chest eontnt rn appear ms a w.iio. aaaa ui fibrous tissue in which are embedded the heart and lungs. In *Lh'1 olass are An types of asbestos and glass xihre that b*w been prepared by gentle grinding. The finding that the method, of preparation of glass flhro senplos can greatly alter the pathogenic effoots of this oust, represents the most interesting results of the year. The glass staples used oontain many small fibres of 250-1OOQA0 in disaster which is within the else range of asbestos crystals. Gentle preparation aethods leave these small fibres undamaged and samples so treated produoe fibrosis with adhesions. Machine grinding appears to break Up the fine filaments faster than the large and these samples produce only granulomas without adhesions. These experiments indicate that the shape of the particle say he aorw important in fibrosis than ita cheaioal nature. Indications at present are that the dangerous particle may ha a fibre several alerona ia length, but only 250 - 1000A in diameter. So far in industrial processes asbestos is the only mntsrixl that has given such partidea, but the use of very fine glass fibre may provide another source of these partioles. Worm in the coming year will ba focused on this point. The results from the pleural cu7ity seem definite. It remains to saa if the same results are obtained from lung tissue. u -u.u *n the method of prc^uc.ua of asbestos bodies During this year a aariaa of experiments has bean oomplatad which give new information on asbestos body formation. Thesa results nay bs summarised as follows:- Asbesloa body production does not occur actually inside calls as we used to think, but betwwsil olosely apposed aaoropha^ss as they are fusing to fttt* giant oslii. Lata* when giant ball fluieo ll eoaplsta APPB1DIX L Report on Work at St, Jamea* Hospital Leeds - Dr. Swiwhurne Animal Feeding Experiments Batobaa of rata bare bean followed Tor 18 months after the ingestion of a oourae of crocldollta duat at two doaw levels. So far, dam of those animals has daveloped any untoward effect*. A number were sacrlfloed early and otherslater but no dusi was traced in the material so far examined either bw light nioroeeopy or micro incineration. Three of the oontro] group java died or beon sacrificed because of natural disease -- one uterine serooaa end two with nephritis. # Similar groups are reoeiving chrysotile dust but in order to avoid contamination, this experiment was started later. So far no tumours have resulted. Asbestos in Pleural fluids , U&crophages containing asbestos fibres sad carbon were found in pleural fluid from one of Dr. Holt's animals. Za tho light of this finding, pleural and peritoneal washings from rats from the above experiments have been seal chad, hut so tor wi*h results. Fluids from two patients have also been negative. This work is being extended by studying acre samples from patients with suspected asbestosis or early mesotheliomai aad material is baing oollscted from such patients to try aad detarmlme whether aesothelionae arwlaatsd diffusely due to m "field change" or la a localised r multifocal way. APPPTOIX S Report on Research la Leads - B.W. Crlmshaw. A.U. H^rrli An Investigation of the breakdown phenomena on grinding chrysotile hu been completed. The release of --has proved most interesting, but it is depei^int on pH ooiWLltions. To overcome this problem, the fires magnesium release has baf& aeeeassd by titration to neutral pH conditions in all oases. The results on one Canadian chrysctila typify the general pattern:-- Sample treatment % magnesium released Shredded only 2.0 0.5 Milled for 24 hours 50.5 2-3 Milled for 72 hours 63.0 2.2 The products cf the milling have been separated into carefully sized -fractions and the release phenomena investigated as a function of particle size. The results of the sample milled for 24 hoars may be compared as follows:- Size range (by settlement) % mesneslum release % magnesium retained 100 - 64 miorons 50.0 50.0 64-15 miorons 48.4 51.6 - 15 miorons 57-4 42.6 A olose analysis of ths results has revealed that a distorted layer is dsvelcpsd on ths asbestos fibres by tbs grinding prooess. Within this lsyer the asgnesina is fires and can readily be released into solution whilst ths silica remains as part of the lattice. The thickness of the distorted layer may ba indepandant of partlels also but is related to the intensity of grinding. The concept of the distorted layer is exactly parallelled by studies of silloosis where a highly reactive layer surrounding ground quartz grains has been postulated as s prims feature. Associated with the release of magnesium is the absorption of organic components such as amino-acids. That thase are absorbed baa been established conclusively but the amount and type of absorption appears to ba dependent on ths pH and buffering conditions within the solution. appeneh g Report on Immunology Study - Dr. Turntr-Tarwiok It is now known that oartaln chronic diseases of tho thiyrold, touch, adrenal gland and other organa arc ralatad to tho dovolopaMfc of immune reactions which in aimpla tana oouaaa tho patient to "rs.lsot his own tissue". York in this laboratory was originally designed to investigate the possibility of antibodies, apeoifie to lung in certain ehronio fibrosing lung diseases of unknown cause and whioh here histological similarities with other so called autoimmune diseases. The olinioal syndrome of Cryptog-nl r Alveolitis was the subject of our first study. The results of this study showed that although long reaotive antibodies could be demonstrated in some cases these invarisbly eroos* reacted with other tissues: in other words they were noa-organ specific tissue antibodies. It has been established by other seiists that there is a group of autoimmune diseases particularly characterised by such antibodies and usually a number of different non-organ specific antibodies can be identified in the sane patient. Antibodies reacting with cell nuclei (anti-nuclear factor or AH?) and thoss reacting to denatured Jf globulin (Rheumatoid factors or Rf) arc two of the most oomaon types found. Against this background of information, it was enoouraglag to find that in Cryptogenio fibrosing Alveolitis ART sad Rf were found 1m about a third of the cases, particularly in tho marc sente phases of the disease. Ve believe that fibrosing Alveolitis is sot due to only one Oxcse, but represents a final oomaon path of pathological change in the lung due to many different agents, fha olinioal' syndrow found in asbestos workers characterised by finger clubbing, widespread crepitations in the lung, widespread radiographic shadows, a restrictive type of ventilatory defect without airways obstruction and fibrosis of tbs alvsolar walls are idontioal with the features of Cryptogenio fibrosing Alveolitis found la patients without asbestos exposure. The next logical atop was therefore to study tissue antibodies particularly the non-organ specific group la the soma of aabostosls patients. Zf they could be identified it would suggest that sou types of immunological host reactivity played a part in the developaent of thisdisorder (in sow or all oases), eithoig* the xaot mechanism of tissue damage would still have to bo worked out. furthes-inn. it i*ht bo possible to identify those patients who ware mors liable to develop lung ohangss and explode thea from exposure before lung changes have occurred. Pesixn of the Initial Stud? Sara from patients with the olasaieal features of asbestosis were collected from as wide a eatehment area as possible to sever different 2 durations and typos of asbestos exposure. It was at this point that the Unk with the Pneumoconiosis Medloal Panel becaae particularly alusble. By the end of the first year 116 sera had been eolleoted and studied (see Eleventh Annual Report). Our results shoved that both AN? and H? wei e fcu^d significantly re frequently than in randan populations witn an inoidenoe strikingly sisilar to that found in Cr7pt=g:nio Fibroin* Alveoolitis. further detailed study vas therefore indicated^ - (a) To obtain further evidence of lmaunologlcal hyperactivity. (b) To ascertain whether tissue antibodies ooourred as a result oi ij-yow .hrcnio fibrosing condition as a non specific reaction to tissue danage. (o) Whether detection of tissue antibodies oould identic those patients at special risk to develop lung fibrosis. further Evidence of Iaaunolo^ioal Reactivity Lung reactive antibodies were studied by three different techniques:. 1. Conventional complement fixation tests, using homogenates of human lung as substrate. 2. The antiglcbulin consumption test using the sane substrate. 3. An indirect immunofluorescent test using H 38 lung fibroblasts. Our results shoe that in asbeatosis, lung reactive antibodies are only very occasionally found using say of these three systems, and this is in contrast to the pattern of antibodies seen in Systeaio Lupus and fibroaising Alveolitis, where these types of tissue antibodies era not uncommon. However, this contrasts with the two other conditions in whichANT'and R? are commonly found, namely Systeaio Lupus Zrytheaatosls and fibrosing Alveolitis where cytoplasoio antibodies esn ooaaonly be detected in complement fixation and anti globulin consumption systems. On the other hand study of tissue antibodies in other ohronio fibrosing dl seayii suggests that AH? and R? do not result nan-speoifleally fro* any type of chronic inflammatory change in the lung and it looks therefore as if AH? and R? are asaooiated with the development of certain forms of fibrosing discs:?: only, including asbestosis* Further evidence supporting the suggestion ef Immunological hsrperreant.'fvitv in patients with asbestosis is found in our results o.' quan titatire immunoglobulin assay where increases in individual immunoglobulins are not infrequently found occurring in a similar prupor-l-n. c.sea and in similar ms to that found in Cryptogenic fibrosing Alveolitis. Survey of Patients with Asbestos Brpoaure To answer the question whether antibodies develop before lung fibrosis will have to be answered by surveying exposed-tubJeote without X-ray change*. Ve have therefore devised e programme to eurvqy patienta 5 exposed essentially to asbsstos la two contrasting ways; ana la a factory populat ion md tba other alloyed la tho insulation of ahlps at tho Hoyai hayax Dockyard, Plymouth. So far 127 Mra fkom tho fhotary * group and about 73 f**-- Plymouth bars booa oolleotod. So-- 400 Author era will b obllected baforo tha datailod analysis lo --da. The initial impression ia that exposed but unaffootod anbjNta even after aaay years azpoaura to asboa'toa *taro aa inaldanoo of circulating antibodies siailer to tha aor--1 population, 1.0. about The problem no* arises as to uhathar it la this ooourrl^ who are at special risk to develop asbestoaiS or uhathar Inns fibrosis together with tissue antibodies appears la prarloualy negative subjects. Our data perhaps best fits with the suggestion that the-- subjects nay be particularly prone to develop asbostosis so that tho laBidoooo of tissue antibodies rises from J)e to JCfi as this group becomes adopted out. but that other factors are also involved aeoountlag fbr tho numbers of affected patients who have no tissus antibodies. Further ffork The immunological surrey of asbestos exposure has to be completed in the laboratory and then analysed. Tho datailod oorrelStloa between the clinical radiographio, physiological faatursa and tho immunological status in patients with asbestosis most bo undsrtakam. This data is already being handled. Tha radiographs are bel ng classified according to the UZCC classification and tha physiological chrysotile -- i'c: Rs.\csuRiG t.u. ruinx KP-maacs? By: Alison D. McDonald, M.D., D.P.H. Department of Epidemiology and Health McGill University, Montreal, Quebec - Presented to the Asbestos Textile Institute at its Annual Meeting held October 5, 1973, at Wychmere Harbor Club, Harwichport, Mass. What are the health risks associated with working with asbestos? In quantitative and qualitative terms -- What is the relationship between amount and type of exposure and amount end type of disease? Although a great deal of research has been done on the subject, the picture is still fairly imcomplete because the main evidence has to oome from observations on man -- on people who are known to have been exposed to the mineral. Other investigations, such ns animal experiments, do a lot to add to the picture but the evidence basically depends on what disease occurs in man and with what ex posures. It is complicated, as you realize, by the different varieties of fibers, and because each fiber type may affect health differently. But I will try to give you some picture of the present state of knowledge, which is, on the one hand, complicated, and on the other, uncertain. Slide 1 shows the main types and quantities of asbestos pro duced and the time period over which they have been produced. It also shows the different uses for the mineral. The first hazard to be observed was asbestosis. In quantita tive terms -- Whet is the risk of contracting asbestosis? How much dust exposure, and over how long a period of time, is necessary before there is a risk of getting asbestosis? The matter is still rather poorly assessed, except in the study we have been doing in Quebec where we. do now have, for chrysotile mining, a fairly good picture of the amount of exposure which will give rise to asbestosis. It appears that all types of fibers and all types of processes (all industrial groups) are at risk of asbestosis. The problem really lies in lung cancer. There are two main cancers that are associated with asbestos -- lung cancer, which is really indistinguishable fro?" the lung cancer that smoking can give you; and mesothelioma, which is a very rare tumor that involves the surface of the lung and the lining of the abdominal cavity. A very definite connection has been observed between asbestos exposure and mesothelioma. The only slides available for reproducing in thi a wx*itt^n recount are shown ns Tablns 2 through 9. Page 2 Chrysotile -- How Reassuring the Mining Experience? TABLE I Main Industrial Croups and Fiber Exposure Mining Manufacture Insu lation Chrvsotile + Not Known CrocidoliLii ++? Amositc ? Anthophvllite + Not Known ++ Not Known Not Known Not Known Jf/A ++ ++ -f+ Table I. I'm proposing to look at this in three main industrial groups: mining, manufacture and insulation -- and at the fiber types concerned, i.e., chrysotile, the three main amphiboles, and mixed fiber exposures. Unfortunately, the latter group is the most common. When we started our studies in Quebec, it was known that very substantial risks of lung cancer and mesothelioma were found in the manufacturing processes and in people working with insulation. This is particularly true for mesothelioma which is very rare and only occurs in one out of a million population -- and yet a substantial number of cases are found with certain asbestos exposures. Substantial health risks in. texuis of mesothelioma and lung cancer have been well documented for mixed fiber exposures. When we began our studies in Quebec, there was little evidence of a serious problem in the Chrysotile mining industry. It was, therefore, very important to look at groups of people who were exposed to only one type of fiber. So we started investi gating all persons who had ever been employed in the Quebec chrysctile-producing industry. The main objective, apart from studying pure Chrysotile exposure, was to determine the dose re sponse relationship; that is to say, to try to get some precise information about what .exposures could be sustained without a significant risk to health, and at what level wr.s there a significant amount of disease. As you know, the two main asbestos mining aroas in Quebec are Asbestos and Thetfora Mines. Slide 2 is a photograph of Canadian Johns-Mar.ville's Jeffrey Mine at Asbestos. Slide 3 is a picture of Smith Street, in Thetford, which is indicative of the extensive environmental exposure to people, locally. Slide U. In starting our survey, we obtained personnel records oi all oi wi.u who ever had *n the mines and mills. We documented all cf their jobs, recorded as well as possible the amount of dust to which they had been exposed, and allowed for the time during which they had been exposed to these levels. We then divided all of these pcoplrf Into groups, accoMing f*- Hi> amount of dust exposure. nor#ilift Page 3 Chrysotile -- How Roassuring the Mining Experience? TABLE II Dust Exposure Levels and Numbers in each Analysis Dust Exposure (mpef - years) -1C 10- 100- 200- 400- 800+ Number of Men in Each Analysis Mortality Study 2810 3329 1124 1007 837 585 Radiographic Study * 1 1522 1133 912 718 707 Lung Function and Respiratory Symptoms 91 455 159 134 109 67 Smokers 69 381 144 117 96 59 Non-Smokers 22 74 15 17 13 8 ism 9692 6529 1015 866 149 The above Table Il/Slide $ shows the extent of the study. Look ing at the top line, we have six groups, ranging from a total of less than 10 million particles per cubic foot .t years through 800 plus. . If you take a lifetime of 50 years of employment, the last group on the right would be equivalent to exposure to an average of at least 15 million particles per cubic foot. This is a very heavily exposed group and, of course, such exposures have only happened in the past and do not occur at the present time. Dr. Graham Gibbs, of the Department, of Epidemiology and Health, has been studying the corre lation between fiber counts and particle counts and we do not find sufficient correlation between the two to give our findings in terms of fiber counts. For this reason and because all epidemiological information is in teras of particle counts, we consider that these . should continue to be used until fiber counts have been done for a long period of time. We do not have any direct information about fiber levels in terms of risks of disease. One of the three major studies we undertook was of all men born between 1891 and 1920, to study causes of death and whrt their death rates were in various dust categories. We did an x-ray study in order to determine which dust groups showed an increased incidence of x-ray changes and e* what level the increase started. This, of course, was important evidence of disease. Laboratory equipment was moved down to the mining areas and 1000 men were submitted to detailed lung function studies, again to see what the relationship was between the amount of chrysotile dust to which the men had been exposed and changes in their lung function. Slides 6_fc 2. show the ftpp.*.ruuo v-'e used to test lung functions. Page 4 Chrysotile -- How Reassuring th: Mining Experience? TABLE III Agc-Corrccted-i* rta.iity by'Cruse Per 1000 Hen Born 1891-1920 Secth_s_ tc December 1969 DpcT y^cuS All Causes Respiratory Cancers, including malignant pleural mesothelioma Abdominal Cancers Pneumoconiosis -10 ]/i_ ICG3 65 355 354 10.3 18.0 1.6 13.1 13.6 1.5 13.4 13.7 0.8 200313 15.5 11.6 4.9 400323 21.4 26.3 4.9 800+ 395 32.1 28.7 23.6 Table III/Slid-. 8 shows the sain results cf the mortality study. Of all causes cf disease, it wr.s only in the highest dust greup (8C0+) that there was a considerable excess of deaths. For respira tory cancers, which includes malignant pleural mesothelioma of which there were very few cases in the industry, a risi is clearly present in the 4CO to 800+ dust groups with an exposure (to an average con centration of 8 mpef over 50 years). The rise probably does begin a little earlier.* The highest dust group, which as we said was very heavily exposed, has about 3 times as much respiratory cancer as tir the people with minimal exposure (the less than 10 greup). The latter group includes people such as these working in clerical jobs and who have virtually no exposure to asbestos. But having inform.-tion for both groups gave us a population with which to compare the people whe were substantially exposed tc dust. There was alsc some- indication that abdominal cancers were related to dust exposure. You will see a higher amount of abdominal cancers in the 400 to 800 and the 800+ groups. The same experience has been observed in other studies. It is by no means certain that this is directly due to asbestos since there are ether possible explanations. You will see that the rise in asbestosis occurs at around the 200 dust level, indicating art equivalent of an average of 5 mpef over 50 years. Table IV/Slide 9. What is thought to be significant disease is irregular snail opacities of grade 2/1. For those cases we observed that a significant increase (recurred in the 100 tc 2CQ dust group. We conclude, that for a lifetime exposure, an average of 2 mpef gives rise tc radiological change indicative of significant disease ir. 1?6 of persons. ol^ue 10. I;. 1. fur.cticn tests in <*i K*'*v'tte smokers and non- smokers, the first change occurred in the capacity to breath in_r.no this started with low levels cf dust exposure. But a lOf' deficit in breathing capacity occurred ct about the sane level as tha radio lo gical changes that I just talked about -- at tlio ,'hv-\. cf 2 mpef on average over a lifetime. A Page 5 Chrysotile -- How Reassuring the Mining Experience? TABLE IV Radiographic Charges - Prevalent Rates () Standardised for Age and Years in Industry -- MalesAged 36-65 at time of Radiograph mpcf - years Dust Group -10 10- 100- 200- 400- 800+ Thetford Mines Average Irregular Small Opacities - - - > /n 2/i is 0.0 3.3 0.2 6.3 2.2 8.7 12.0 17.2 7.6 0.9 2.4 9.2 2.0 Pleural Thickening- Grade 1 2.4 4.6 6.5 5.8 8.3 10.5 6.4 Grade 2 1.3 0.7 0.6 1.2 1.3 2.0 1.1 Asbestos Irregular Small Opacities - - - 1/0 6.4 3.7 6.3 5.0 6.8 7.0 5.1 2/1 0.0 0.4 1.5 0.8 0.6 3.9 0.6 Pleural Thickening- 0.0 A.UGrade 1 2.9 2.6 3.0 3.0 4.7 5.6 3.2 Grade 2 0.6 0.5 1.4 0.7 0.7 TAPLE V Age-Corrected Prevalence Rates {%) for Bronchitis and Breathlessness by Dust Exposure k cumulative Spoking Habits Dust Index mpcf - years -10 10- 100- 200- 400- 800+ Bronchitis Never Smoked 10 19 19 46 21 49 Up to 100 Cigar ette Tears 18 0 12 0 46 0 100-499 500-999 1000 41 28 21 33 42 43 38 44 28 47 58 100 47 45 55 54 35 Breathlessness Never Smoked 0 14 24 31 13 44 Up to 100 Cigar ette Tears 0 12 >o 21 41 43 100-499 16 14 8 20 42 18 500-999 1000 9 19 21 19 14 39 0 23 27 31 34 46 more Page 6 Chrysotile -- How Reassuring the Mining Experience? Table V/Slide 11. Lastly, the workers were asked to fill in e questionnaire about smoking. From the answers, wo found that thorn was a relationship between breathlessness and dust exposure not apparently affected by smoking. But if you lrok at bronchitis and along fcha line for the "never smoked" and the two groups of smokers, you will note there vjacr.'t any change in bronchitis which increased asbestos dust exposure. Now, if you lock at the columns vertically you will see that smoking does a of damage in terms of bronchitis TABLE VI Distribution of Cases OX Me jO &ijc ax\j'Ufi 1/^ Year of Death erd Province (1960-1970) I960 1961 1962 1963 1964. 1965 1966 1967 1968 1969 1970 Ontario 0 1 4 9 6 7 8 6 7 12 "5? Quebec 6 6 4 3 8 7 14 13 18 7 16 "TM Other Provinces 9 3 5 7 3 5 ? 6 7 6 Canad 15 10 13 19 17 19 31 25 32 25 "2$ Annual Incidence Per Million Popu lation 1966-1970 1.2 2.3 0.9 1.4 Reviewed by Pathology Panel 57 to 47 194 Accepted as Mesothelioma 71* 42* 57$ 55* Table Vi/Slide 12 . The other study we did was to survey all mesotheliomas in Canada. At the outset, I should say we had just 5 mesotheliomas out of 3270 deaths in the mining industry. Although this may seem to you to be a small number, there should be no cases of mesothelioma in a general population. One of the problems about mesothelioma is the diagnosis. There is by no means agreement among pathologists about the diagnosis of mesothelioma: so our finding of 5, having searched pretty thoroughly for mesotheliomas, may well be an over-estimate, especially because they were particularly looked for in neople with known asbestos dust oxposure. Having found very few in the industry, .e aid a concurrent stuuy -- locating all the mesotheliomas we could in Canada. Wo obtained from all pathologists reports about all known cases and feel wc got fairly full ascertain ment. The ascertainment wasn't done until 1967-68. If you leak at the graph at tho top (Table VI) you will sec a gradual rise in the annual number of mesotheliomas across Canada up to 1966. This is * Page 7 Chrysotile -- How Reassuring th<_- Mining Experience?.- probably due to poor memory and lack of knowledge about mesotheliomas in these earlier years. We arc continuing this surveillance, end between 1966 and 1970 there doesn't appear to have been any change. This is rather a short, npriod of time and we obviously need to know whether this v;.o change" situation will continue. As you know, the big concern is the lengthy latent period for mesothelioma to develop and the widely expressed fear that we are now going to reap results from exposures which occurred 20-30 years ago and that the rate of mesotheliomas may rise. Wo now fael quite happy that a fairly good base line has been established for this surveillance and we shall be able to know within the next few years what is happening in Canada. If you look - at the bottom line (Table VI), we looked to sec whether mesothelioma occurred mere in one part of Canada than in other sections of the country. There was, in fact, more in Quebec -- over 2 per million population, compared with just ovar one in Ontario and slightly loss than one in the rest of Canada. But wo must revert to the question of the diagnosis. When the mesotheliomas were submitted to patholo gists, a much lower proportion was accepted as mesothelioma oy the pathologists' panel -- r.ct only in Quebec but in all of Canada. It looks as though, for cases that are accepted by the panel as mesotheliomas, there s or no ui.i<ei ciiwc m cue various p&i i* of Canada. TABLE VII Distribution by Age of Cases and Matched Controls (The number in parentheses designates these successfully investigated, epidemlologically) Age (Years) Men Cases Controls Women Cases Controls 20-29 30-32 Ic -4$ 50-59 60-69 70-79 80-89 90-99 C -) l fl 12 (]L2) 8 8) 7 [7) 2 2) 1 (1) Total 39 (37) Mean 58.7 Standard Deviation 12.9 0 (-) i ill 12 (11) 10 (10) c i\ 3 (3) 1 (1) 39 (38) 59. l 13 2 2 (2) ilil 6 (6) 6 (6) 7 (7) 3 (3) 32(32) 58.9 18.2 0 (-) i fel 5 (5) 8 (8) 8 (8) 2 (2) 32 (32) 59.0 15.2 Table VII/Slide 13. There are two objectives in this mesothclicstudy -- to continue to watch the incidence and tc examine to what extent the mesotheliomas are caused by asbestos. Here you sec that more than 2/3 of the cases are in males, as 1s expected, and more.... LM^_ S#-4- Page 10 Chrysotile -- How Reassuring the Mining Experience? Table II: If you will look at the top line, you will note that we did find s"mc indication of domestic exposure. There were e few people who had teen exposed to a lather or a husband working with asbestos. The diagnosis of mesothelioma may be more likely to be made in such a situation, but nevertheless, this risk is probably real and, especially for children. Eut there is no indication that is at any risk. So we found that the mesothelioma study backed up what we found in the mining industry, namely that there is a small excess of mesotheliomas in mining but it was manufacture and insulation that were mainly associated with mesothelioma in Canada rather than the mining and milling of chrysotile. This has been borne cut in other studies of chrysotile mines in Cyprus, Northern Italy and the USSR. Although the information is somewhat imcomplete, they indicate a similar experience to that found in Quebec with regard to lung cancer and, in fact, practically no mesotheliomas. The evidence, insofar as the chrysotile-producing industry goes, is good in that, the r-i^ks are low. and probably controllable. Now, referring back to Table I -- I'm going to put a + for chry sotile mining. For anthophyllite mining in Finland, the picture is similar in that they find nc mesotheliomas in that country. There does appear to be some lung cancer associated with mining but it isn't the high rate that appears in manufacturing and in insulation work. Our information about crccidclite and amosite mining is frag mentary because it doesn't depend on surveys of people working in tjie mines. It depends, rather, on a surveillance of all types of cases which come from the mines and surrounding areas. It docs appear, however, that there have been a substantial number of mesotheliomas around crocidolite mines in the Northwest Cape. So, I'll put a ? fer crccidclite mining (Table I) because the evidence isn't toe secure, especially in regards to rates; i.o., how many cases in relation to how many workers and residents. Regarding the amesite mines in the Transvaal, there is a very minute + (Table I). There docs appear to be some lung cancer but practical.^ . -.tfautuQlicma -- vkl-h ' : -ry different from the Northwest Cape arcs. The relationship between mesothelioma and chrysotile has beer, confirmed in studies by the electron microscope -- studies in whirl: fiber types in the lungs of cases of mesothelioma have been identi fied by Dr. Free Foolev, of Cardiff in South ><rlas. In thesi samim, pracr.i 1 iy .-11 of the f .' s drtocaod *.? t ' ha | M- core .. A Page 11 Chrysotilc -- How Reassuring the Mining Experience? bole variety. So far it has not been possible to distinguish crccidolite from fibers, but chrysotile can be defected. Ail the ccrras thus far expired have substantial amounts of a.nphi* bole fibers and relatively few chrysotile fibers. There ere reports that persons exposed to chrysotile only in the manufacture of asbestos, have had similar rates of mesothelioma and lung cancer .uuna m persons exposed to a mixture of fibers. The evidence isn't any too sure, in fact it's pretty doubt ful, that these men were exposed only to chrysotile. So, we must put a ? (Table I) against the risk cf cancer in the manufacture of asbestos products using only chrysotile. Some additional contents to the data in Table I: Dr. Selikoff reports a high rate of mesothelioma and lung cancer in persons ex posed only to amesite. Information on the manufacture cf antho- phyllite is unknown because single types of fiber have not been used in tho process. Mixed mining is not applicable. And, we lack satisfactory information about manufacturing with pure c-o-r*dolitc or with pure anthophyllite. As you know, there are differences in the nature of each fiber type but experimental work has produced some possible explanations of the varying effects. Chrysotile is a long, thin and curly fiber and there is some evidence that it easily gets held up in the >larger airways and, therefore, does not penetrate so well as other fiber types which can enter the smaller airways and reach the pleural surface. In comparing crocidolitt and amesite fibers, both ere straight, rather than curly. However, when mined they apparently have quite different diameters; crocidolite having the narrower diameter and emosite being much wider in diameter. This fits in quite well with the findings from studies in the Northwest Cape. There are a lot of mesotheliomas in the Northwest Cape where the diameter cf the fibers is small; whereas in the Transvaal area, where amesite is mined, and the fibers are broad, there appear to be practically no mesotheliomas. This doer.n't fit with the stcry of the manufacture of noositc, and, frankly, I really dc not know the reason. Fiber differences could be an explanation; but on the other hand, the big differences between chrysotile mining and the manufacture of asbestos products and insulari-n cannot be laughed off. Set... of the possibilities for the differences between chrysotile mining and manufacture and insulation are .... 1) It is possible that during manufacture the fibers may be broker, up ir.t^ much smaller pieces and, therefore, lese their i capacity to be caught up m the bigger nliva.ys, then:by penetrating further ir.v the lungs. Page 12 Chrysotile -- How Reassuring the Mifdiig Experience? 2) It is possible that the culprits are crocidollte and/or amosite. 3) It also is possible that in the process of manufacturing and insulation rHat ether carcinogens are involved. Smoking has been raised as a possible additional factor in causing cancer of the lung; but for mesothelioma it has been pretty clearly shown that smoking is not an added factor. If there is something else that increases the risk of mesotheliomas, it is not sacking. So I *13 VC tG conclude that the chrysotile mining experience cannot really be said tc be reassuring. It is certainly possible that if one were able to show that the manufacture of pure chrysotile gave cancer rates, similar to those in mining and nilliag, th pic ture would certainly be brighter. But, it isn't brighter at the moment! - end -