Document aBDZpQ9RREj1B19w55YpMZ3qN

sivfca ASBBSTOSIB B-KSHAPfig COUNCIL ( gimWTH ANNUAL REPORT FOR THE TTOVg months BB&NNING lat OCTOBER. 1967 1. DCTBODOCTIOW The labestasis Research Council ess est&bllshel on the 1st Ootober, 1957* This report detsils the aotivltles sponsored by the Council during the eleventh year of its operation* 2. CONSTITOTIQM The Constitution was revised in August 1965 to extend the field of activities to asbestos operations other than textile and to provide for the admission of Assooiate Members as veil as Full Menbers* The Membership of the Council during the year was as follovs jZaUJteskau B.B.A. Croup Limited. The Cape Asbestos Company Limited. ( Turner A Bewail Limited. Home Associate Members The Atlas Stons Company Limited. Bell's Asbestos and Engineering Limited. T.B. Ford Limited. (In plaoe of Birfleld Limited). Riohard Xlinger Limited. The Universal Asbestos Manufacturing Company Limited oeased to be an Associate Member on becoming part of the Cape Asbestoe Company Limited. Overseas Associate Members James Handle A Coy. Pty. Ltd. Jahns-tfauvllle Corporation. The Quebeo Asbestos Mining Association. Criqualand Exploration A Finanoe Co. Ltd. /oont'd... ( ALV 0008200 (o) Dust Control Co--^ Chairman : Ur. J.M. Ucfarlan* Ur. S. Boyes Ur. T.T. Anderson Ur. P.B. Bugs* Ur. R.H. lilsoa Ur. T.P. Baablin Seoretary x Dr. 3. Holaes - Tbs Cap* Asbestos Co. Ltd B.B.A. Croup Ltd. - The Cape Asbestos Co. Ltd Turner A Kswell Ltd. - Turner A Kswell Ltd. - Turner A Hawaii Ltd. Turner A Hawaii Ltd. This Committee was re-constltuted la July, 1966, as the 'Bnvironmental Control Committee1 under the Chairmanship of Ur. A.A. Cross. It held its first meeting on 22nd August, 1968. Dust Control Committee aestings were held as follows x- PIHAHCB Roohdale Hebden Bridge - 24th January, 1963 - 5th June, 1968 (*) rur Arrangements The finances of the Counoil hare oontinusd to be administered through accounts operated by the Boohdal* Branoh of the Dlstriot Bank. (b) Budget and Expenditure Counoll Budget Expenditure 23,500 19,130 LIAI30M WITH OTHRS INTBRB3TKD BOPTwa Contaot has beea maintained with H.U. factory Inspectorate and the Panel convened by the Senior Xedleal Inspector of faotorles, on whiob two of the Counoll's Medloal Offioers served, has published Its Report entitled 'Problems arising troa the use of Asbestos*. Liaison has continued with the Pneunooonlosis Researoh Unit of the Uedieal Researoh Counoll. The opportunity was taken during the nesting of the Researoh Committee at Cardiff la May to ham a joint one-day nesting with the Unit to discuss ooaaoa problems. Arrangements have been put in hand to organise a joint ARC/PKU Conference in April, 1970 on 'The Tissue Reaotion of Asbestos'. /oont'd... ALV 000820? 4 The Sub-Committee set up by the Hygiene Committee of the British Occupational Hygiene Society, on wfaioh members of the Council served, published a Report in April 1968, entitled 'Hygiens Standards for Chrysotile Asbestos Dust'. Liaison has also continued with the O.S. Publio Health Serrioe and with the Air hygiene Committee of the Asbestos Textile Institute* 7* RESEARCH FPOCaJOflCg The researoh work of the Council was further expanded during the year by Crants to Dr. Margaret Turner-Varwiok of the London Hospital of Diseases of the Chest and Dr. Margaret Swinburne of St. James' 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 many of the sections are still to be examined. The studies on the mechanism of asbestos body formation have also been oompleted. Collaboration with the Institut fdr Luf .aygiene in Dusseldorf has oontlnued. (li) The jolleotica of biopsy matsrlal from suspeoted cases or human mesothelioma has continued and the production of mesothelial tumours in vuaals has been further studied. Tork on the pathogenicity of minerals other than asbestos has been started. Collaboration has oontlnued with Dr. Cross of the 0.3>. Industrial Hygiene foundation in Pittsburgh. (ill) Preliminary work on the effeot of *abestos on lysosomal, cell systems terminated in June, 1968. (iv) Work on the surface properties of asbestos h* i oontlnued. (v) An immunological study has been started but only preliminary results are yet available. (vi) Animal experiments on the ingestion of asbestos have oomoenoed and it is doped to have some resulte in the next twelve months. /oont'd... ALV 0008203 -5 DOST SAMPLING AND AMALTS IS Mhile the Royoo Autometio Particle Counter hu oontlnued to be uaed as a routine monitoring instrument, the fibre count by membrane filter has remained the standard method in the industry. The method has been published by the Counoil as its Teohnioal Kota Ko. 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 Government Departments and a meeting of those involved was oonvened by the Ministry of Technology in May, 1968Representatives of tbs Counoil were present. During the year, the Council has carried out a survey to detemlne the level of asbestos dust in composted buildings of various types in which asbestos produota have been incorporated in their construction. 1 report ai been prepared for publication. DUST CONTROL During the first part of the year, the Dust Control Committee oontlnued to work on various problems affecting the m&nufaoturlng and appli cations siie of tha Industry. In July, 1?68, however, this Committee was reconstituted with thr title of 'Environmental Control Commit tee' end with wider terms of reference to enable it to deal with all relevant matters likely to affeot the Industry and its customers uder the Hew Asbestos Regulations. THE WEI ASBESTOS RXGULATI0H3 In April, 1968, representatives of the Council were called to a seating at tha Department of Employment and Productivity to diecuss the Council'a comments on the preliminary draft of tha Hew Regulations. It was learnt that the Council* suggestions were likely to be given consideration in framing the Statutory Draft, in particular the replacement of tbs *no dust* oonoept by a more praotlral approaoi to the problem. The Statutory Draft was publisher in August. 1 ?68, and tha Council again fait obliged to make a number of comments, which are atill under discussion. COPES OP PRACTIC1 During tha year tha Council issued ita fourth Code of Praotioe - 'Beooaaended Code of Preotloe for Handling Consignments of Asbaatoa Tlhro in British Ports* /cont'd... ALV 000eZ04 -6 The demand for copies of all Codes of Fraotica has continued steady. 12. OTHER PUBLICATIONS "The Mechanism of Formation of Asbestos Bodies" S.K. Botham and P.F. Holt, J. Path, and Bact. Vol. 96, Ho. 2, p. 443. Interaction of Poly-2-Yinyl Pyridine 1-Oxide and Poly-4-Vlnyl Pyridine Oxide with Monosilicic Aoid'' P.F. Holt and S.P. Nasrallah, J. Cham. Soo. 1$6d, p400 13. PULMONARY PUHCTIOK TBST3 The work done by the Member Companies in this field has continued to be reviewed by the Research Committee. 14. VTSIT3 In November, 1967. Mr. faddell. Dr. Case, Dr, Knox, Dr. Smither, Dr. Beattie, Dr. Davis and Dr. Holmes attended the Second Antigua Conference organised by the Quebec Asbestos Mining Assooiation. Dr. Addingley, Dr. Knox, Dr. Smither, Dr. Davis, Dr. Holt, Dr. Lewlnsohn, Mr. Hunt and Dr. Holmes attended the International Conference on the Biologioal Effects of Asbestos held ix Dresden in April, 1968. 15. CHTBRAL Dr. Knox has continued as Medical Consultant to the Council and has attended the meetings of th* Management. Committee and the Research Committee. Dr. Beattie has continued as Ra-earoh Consultant ana. has attended the meetings of the Re.sarch Committee. M_V 0006205 APPENDIX , Report on Research at the University of Reading - Dr. Holt During this year most of the long tern experiments started 2 to 3 years ago, in which guinea pigs 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 now available, however, a library of sections in which the effects on the lungs and lymph glands of reasonably small doses of inhaled amosite, anthophyliite, ch~ysotile and orocidolite can be studied. There is also a series of slides in which guinea pigs are oompared with rats that have Inhaled asbestos. These are unique. The following tentative conclusions need to be confirmed. The asbestos dast is first deposited in the bronchioles, the longest fibres (up to 70/i long) in the terminal bronchioles only. Remarkably, seme fibres subsequently appear to move int the alveoli which is contrary to whit 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 amosite and c-ocidolite but none in those that received anthophyliite, chrysotile or glass fibre. No ulear morphological difference been observed between the asbestos bod es prod : i on the four types of asbestos; these produced by glass fibre are similar except that, sinoe they fora roi. d single fibres r." her than fibre bundles, they are usually s--*i_ier. I;'. a search of other : -gans for evidence of transpoi * of asbestos from the respiratory sy am in a guinea pig, so far od pa.-feotly for~ad asbeet js body has been fc-.nd in the thyroid gi>nd. The studies on the mechanism by whioh asbdstos bodies are 'reduced hare now been completed. The initial effect of the fibre ~~ lu ;ne lung 10 the produotlon of haemorrhage and the resulting u o -oontairdng compounds from tie haemoglobin in tbs red oells are taken up )y dust oells and deposited on an asbe j ;qs fibre la the same sell. The production of an asbestos boiy does not therefore depend on the_ chemloal nature of the fibre and we have produced bodies from mioa fibres and very fine glass fibres. This last experiment is being extended and some guinea pigs have been madu o inhale glass fibre and other* glass pc'-<-er of tbs same chemical coc::c sition. An experiment has been concluded whica was set p to investigate wco'cer the progress of pneumoooniosis due to asbestos could be followed 1a animals by ohemieally estimating the collagen forced in the damaged lur 5. The results are disappointing; the variatica between if it least as great as the variation caused by small doses of asbestos. /oont'd... PLV OOOPPOP -2- Now that the fundamental work 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 polymerio substance such as poly-2-vinylpyridine 1-oxide, which has proved effeotive in silicosis in animals and on whether this polymer can alter the rate of fragmentation of asbestos bodies. The possible ooating 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 well under way and early results will be reported during next year. ftl_Y 000820? APPENDIX 2 (cont'dl calcified pleural places, histologically very similar to those found in human cases. In the mice the pleural fihrosis had often developed to a degree where the pleural caTity was completely full and the lungs encased by masses of fibrous tissue. The macroscopio pioture was exactly that of a mesothelioma, but histological examination showed no signs of neoplasia. It would appear that this massive fibrosis is caused by a turnover of dust. When the initial dust granuloma ages the macrophages and g&xnt cells die and are replaced by fibrous tissue. The asbestos dust is left behind among the collagen fibrils and is rephagocytosed by a new generation of macrophages that aotively penetrate the films tissue to pick up the lust. This turnover process appears to continue as long as dust is present and very large masses of fibrous tissue eventually resulted. There is one type of fibrous mesothelioma that pathologists find often difficult to distinguish from normal fibrous tissue. These fibrous masses are in fact only considered tumours because they grow to s very large size. From the mouse evidence it is possible that they may not be tumours but normal fibrous tissue constantly stimulated to new growth by a relatively indestructible oontent of asbestos dust. Experiment to test the pathogenicity of minerals other than asbestos During the last twelve months the following minerals have been tested by intra-pleural injection in mioe :- Tslo, serpentine, bruolte, magnetite, pyroxene, olivine, forsterite and ohlorite. So far, all thesa minerals have failed to produce lesiona other than '.he normal foreign body reactions. The results of injection experiments with fine glass fibre (dla. 0.05ytt) and oalcium silicate are still under review. Follow-up experiments involving inhalation pu all these materials are planned. Experiments with P20k During the first part of this year experiments continued whloh vire designed to test the effect of P204- on the development of asbestos leUons in guinea pig tissue. With the chrysotile sample used, no difference could be found between animals treated with dust P20i* and tnose that had reoeived dust only. For this reason, the experiments were terminated In Maroh* During September, however, soma experiments were started using samples of synthetlo ohryaotile injected latreperltoneally Into aloe. This dust has proved much more to^o than normal asbestos, and it may be worth repeating the P204. experiments with this lust. Experiments to determine the ohemioal processes of asbestos body formation Two studies are at present in progress in this flsld. These involve the electron miorosoope examination of very old oaloifying /oont'd... ALV 0008206 ifPgfPg 2 (confab asbestos lesions and Tery young lesion* in the guinea pig pleural cavity. Normal asbestos bodies are produced intracellularly and perhaps as few as one in one thousand fibres of dust ever become ooated. It has been found, however, that in old calcifying lesions, whioh are acellulu* and where the dust is now lying free among the collagen fibrils, all asbestos fibres become coated with a layer of material about as thick as the normal asbestos body ooating. This coating is ouch less dense than the 'ferritin* of normal asbestos bodies although some 'ferritin' granules may be present among the other coating material. From a study of the substances known to occur in calcifying tissues it appears most likely that this ooating material is a oucoprotein or suoopolysaccharide. Since colloidal iron is a well known stain for onoin, and is effective beoause the iron selectively Impregnates the mucin, it begins to appear likely that asbestos body formation may be a two stage process, an initial coating of muooprotein or Bruooploysaochari.de being followed by the impregnation of this material with 'ferritin'. The density of 'ferritin' in normal asbestos bodies might be due to its high oontent in living granulation tissue, and the low content in the calcifying tissue bodies may be due to lack of 'ferritin* in these dead avascular area. in examination of very early asbestos lesions is now in progress and already some dust fibres have been found in giant oells ooated with low density material containing only a few. granules of 'ferritin*. 000B209 APPENDII Bwort on Besearch at the Stranaewava laboratory - Dr, Barrett (Work terminated. June 1968) Work on Macrophages It has been found possible to maintain mouse peritoneal maorophages for six lays in Medium 199 (Burroughs Wellcome) supplemented elth 10JS unzuccled calf serum in an atmosphere of 57* CO2/95^ air, on coverslipa, but a serious difficulty arose in that the available assay techniques proved not to be sufficiently sensitive to detect the release and synthesis of enzymes by the small number of cells (a few million) that could be isolated and maintained. A more sensitive method has however, only recently been developed ana this should prove invaluable in future experiments of this nature. The effeot of Chrvsotile on the Stability of Lrsosames A rat liver was homogenised in 0.25 M sucro*-, and a mitochondrial lysos aal preparation was obtained by differential centrifugation. This was suitably diluted and lnoubated at 37, either alone or with a rather dense suspension (10 mg/ml) of finely milled ohrysotlle asbestos (supplied by Dr. P.7, Holt). Over a period of three hours, the mixtures were gently agi tated and samples war- removed periodically and centrifuged. Determination of the ensyms activity in the supernatant and sedimented fractions gave a measure of the extent to which the limiting membrar.es of the Itsusomea had broken dovn, under eaoh treatment to release enzymes in a free, iliable fora,. Worker have shown that quarts can a.t by rupturing lysosomal membranes it seemed likely that asbestos would have a similar effsot, in view of its haemolytio aotivity, whioh was comparable with that of silica, but aa suoh effsot was deteoted) parallel release of mold proteinase was obtained In suspensions with or without asbestos. In view of a reoent Geraat report on the action of asbestos on lysos* aea in vitro further experiments of this type might be justified. The Cellular Consequences of Phagoortoals lysosomes form the digsstive system of cells. and in many ways this is oomparabls with that of higher animals. Whan a macrophage engulfs a baoterlua, it is enolosed in a digestive vaouole, or phagosome, the oontants of whioh are acidified. the lysosomal enzymes, whioh are eotive under aoid oooditiona, are then secreted into the vaouole and the baoterlua is digested. It is known that the biosynthesis of the lysosomal enzymes is stimulated by the prooess of phagooytosis in maorophages (and the same may well apply to tho macrophages that take up asbestos, if they survive). It is not /oost'd... 8l_V 0008210 APPENDII 3 (ccnt'd) thought that this Is solely a characteristic of phagocytio leuoooytes alnoe various tissue cell types oaa show phagocytosis and a lysosomal response. In tissue culture. Generally the lysosomal digestive enzymes produced In response to the phagooytosls are not oonflned to the Interior of the cells, but are released Into the culture medium, and in organ cultures of carilaglonous bone rudiments the result is an extensive digestion of the extracellular matrix strongly reminiscent of that seen in rheumatoid arthritis. Zt is felt that excessive lysosomal activity of this kind may well be involved in the pathology of rheumatoid arthritis end certain other conditions, and investigations have been done on the way in which endocytosls (a general term including plmooytosis and phagooytosls) stimulates the synthesis and release of the lysososmal enzymes. The biological system used is one in which chick embryonic limb bona rudiments are oultered in a synthetio medium to which suarose has been added. Surprisingly, the oelli are unable to metabolise sucrose, and it causes the formatlot; of parsistant large digestive vacuoles within them, but there is no oell mortality and cell division is soarcely Inhibited. There is, however, a dramatio increased in the release of lysosomal enzymes. The radiochemical mioroassay is dtsigned to follow tha time-course of the new synthesis with precision, and an inhibitor of protein synthesis, cyoloheximlde, is being used in an attampt to deoida waat proportion of the ensyme release represents newly-formed, as opposed to pre-existing molecules. Further ork has to the preparations of a pure rabbit anti- ohicken sold proteinase antiserum rJr. t whioh u is hoped Isolate minute amounts of the erz/ae synthesised in culture in the preseno of radioactive traoers, as tha iomunopreoipltate. This would allow ohanges to be followed in the speolflo aotivity of the released enzyme which could give valuable insight into the meohaaism of the ~ stimulated release. ALV 0008211 ~ru.yjjJk. 4- Report on Basearoh at tha University of Leads - Dr. r1a*haw During the last twelve months period the research programme has been directed mainly to studying tha ralaasa phenomena of magnesium and silioon from chrysotlla ondar a r&riaty of conditions, i raw Canadian fibre was salectad for detailed analysis, but other samples have bean shown to possess similar oharaoteristi.es. Both magnesium and silioon oan be extracted from raw fibre under sost pS conditions. The amounts ware greater in acid solutions but tha ratw jf KgO ; oiC^ 1a solution boro relationship to tha stoohiometrio composition of the parent mineral. Onoe the fibre had been ground, the amounts of cation release lnoreased enormously and to a far greater extent than would be expected from simple surfaoe area considerations. Chrysotlle which hai been ball-milled for a few hours still possessed a typical fibrous habit when examined under the mioroscope, but it was possible to extract virtually all its structural magnesium. C-'amlnutlon ;recesses also caused m-i.-lced changes in X-ray, infra-rad and differential thermal patterns. Perhaps the most significant observation of the release phenomenon in treated chrysotlle is the faot that the absorption capaolty of the mineral, was lnoreased considerably. 5-jt only was water absorbed but also cations 'her than magnesium and many organ!o compounds and complex.*.-. Stearlo sold and oae amino-acids were absorbed and -ha neohanism inrolrsd ohemical as well as physioal pnenomena. It has bsen shown by infra-red >indies that the .'-axacterlsti. spectra of certain organio groups changes markedly when abaorbed onto the treated ohrysotile fibres. ai V arfSNDIX S Beoort on Immunology Study - Dr. Turnar-JTarwiok In collaboration with Dr. Parkas of the Pneuaoconiosis Medical Panel, patients referred to the Panel for assessoent hare been ezaained in person and it is hoped that this speoial series will fora the basis of a long-term follow-up stud/. In addition blood sera supplied b/ co-operating ohest clinics and Industr/ hare also been examined. Included in the stud/ so far have been 53 patients and 11^ blood sera samples* Antinuclear factors and rheuaatoid factors hare been studied. Using the double-la/er immunofluoreseent technique, 20jC were found to be A.N.f. positive, against an ezpeoted figure of 5JC in a * normal* population* Assessing rheuaatoid factor by the differential agglutination titre technique (DAT), the percentage DAI positive was 37, against an expected lass than in a 'normal* population. Uaiag Latex ?11 taste (Latex RA), the percentage positive was 39* Antinuolear factors and rheuaatoid factors have therefore been demonstrated more frequently than expected by ohanee in patients with asbestosis* furthermore, the incidence of these antibodies is. remarkably similar to findings in idiopathio fibrosing alveolitis* The next stud/ is to analyse the clinical, radiographio and physiologioal features correlated with immunological re-activity. A searoh for lung reactive antibody haa been undertaken in 24 patients using the antiglooulin consumption test (AC-CT). It appears that antllung reaotive antibodies are present only in low.titre and are unlikely to be an important laaunologioal finding la asbestosis. Imsunofluorescent studies have been carried out on thres asbestotio lungs. There was no evidenoe of antibody nor ooaplement fixed to any structure surrounding asbestos bodies within the lung. general Conoluaioa Circulating non-organ speciflo tissue antibodies have been found in patients with asbestosis. Moreover the incidence of these is similar to that found in fibrosing alveolitis. These finding! suggest that a similar immunological stimulus ooeurs during the development of both these lung diseases. Whether the immuno3.ogioal response is damaging or proteotivo is unknown. An attempt to get further evidenoe for or against a pathogenstio role of these antibodies (or som# immunological reaction occurring pari passu with them) will now bo sought through a study of those antibodies in different stages of evolution of the disorder, using olinioal, radiographio and physiologioal data as the yardstioks to assess the extent and severity of the disease. ftLV 0008213