Document z0mOwnKDBdm9Xdw0m6kQnxbR

!l Ttde Biological Ejects off Asbestos :i I An i.;ten3Cj;;o:ial symposium organized by I.A.3.C. r' Lyons (France), 2-5 October 1972 A Report by J.C. Gilson, Periarth, UK -r-r 'ini'J. -OCTy.TE-r~ t-xmlT".:-L-iagwr-TL-l .:r-"^T^ta~,~'^^rganegr. I .J A group of representatives ftom 20 coun tries met at the IARC. Lyons, from October 2-5, 1972. Tire meeting was organized by Dr. P. Bognvski (IARC) and Dr. J. C. Wagner (UK). Dr. J. Ilifginson, Director of the IARC, in welcoming the group whose meeting would Inaugurate the new conference hall, said that the aim of the meeting was to assess current knowledge about asbestos cancers and progress towards meeting the Recommendations of the UICC Working Croup on Asbestos and Cancer in 1964. Since 1970 the responsibilities for the ad hoe UICC Committeo had by agreement been taken over by the Agency. Common membership of Committees concerned had ensured continuity of policy. The IARC had been supporting work on asbestos cancers at part of the wider programme of investigating environmental carcinogens (IARC, 1970, 1971). Research Into asbestos cancers provided opportunities of international co-operation and experimental studies to complement the epidemiological evidence in man. Asbestos is mined in many different countries and exposure to the four main types of fibre occurred most often during extraction of the fibre in pure form from the rock. Differences in risk for the different types of fibre, if they could be established, would be of use in prevention. Production could be concentrated on the safer types of mineral. Most of the asbestos-associated cancers seen in man could also be produced In animals. Animal experiments could, therefore, be used to test hypotheses arising out of epidemiological or other research. Dr. J. C Gilson (UK) In an introductory paper, referred to the success achieved in the adoption of the 1964 UtCC recommendation on the standard reference samples of asbestos; the development of an International classifi cation of the radiographic appearances of ssbestosls and the establishing of the Interna tional ans national panels of pathologists interested in the asbestos cancers. The work or the group covered five main topics : 1) A critical assessment of the methods used to delect, measure, and study the effects of asbestos in man and animals; 2) The epidemiological evidence of differences In risk of asbestosis and cancers of the lung, pleura, peritoneum and other sites related to occupation, type of asbestos fibre and other factors; 3) The severity and significance of the asbestos burden present In the. lungs of occupationally-exposcd individuals and mem bers of the general public; 4) A conside ration of possible mechanisms of induction of tumours by asbestos; 5) The uses of asbestos by the community and the value of a cost/bcncfit analysis relating safety, health, social, and economic indices. Fifty review papers had been prepared and prccirculated. " It was clear that the earliest detection of effects of asbestos on the lungs required clinical, radiological, and lung function tests (Dr. Ilarriea (UK) Dr. II. Bohllg (FDK). Dr. M. R. Bccklake (Canada)] but II was still not certain whether there was a definable stage at which progression ceased if there was no further exposure to the dust. Many methods for assessing asbestos bodies in the lungs had been compared, no one method was clearly the best, the easiest to use therefore seemed preferable. There were large differences in numbers of bodies reported on the same tissue by different observers but all methods detected differences between different lungs. The number of bodies was least in rural and highest in urban areas (Dr. P.D. Oldham, UKX Dt. F. D. Poolcy (UK) and Dr. Linger (USA) cmphasued the large number of submicroscopic fibres only detectable by electron microscopy. There was general agreement on this. The positive identification of the type of asbestos still requires more than one method. Quantification of the amounts of chrysolite, crocidolite, and amosite separately when present together in tissue is not yet practicable. A possible means of performing this, using differences in magnetic and other properties of the fibres, was suggested by Dr. V. Timbrel) (UK). Dr. K. F. W. Iliuson (UK) and his colleagues proposed a revised scheme of classifying the severity of asbestosis pathologically to replace 1964 proposals which had been found unsallsfaclory. Dr. W. T. E. McCaughey (Eire) showed that even skilled observers differed considerably in their diagnosis of mesotheliomas, and that an experiment to determine why this occuneJ by recording detailed features of the sections did not provide clues as to how to improve the agreement. Dr. B. Butler (UK) showed how useful cytology of the pleural fluid could he in diagnosing mesotheliomas. Ilistochcmical ami chemical detection of hyaluronic acid was discussed by Dr. Kanncrstcin (USA) and Dr. Ilavcz (France). The electron microscopic appearance of hyperplasia and neoplasia of the mesolhelium was demonstrated by Dr. V. Suiui-.i (USA) and Dr. P. Stocbncr (Fr). The usefulness of long-term survival experiments In ral.s given asbestos by various routes and the opportunities provided in organ cultures of lung and pleura were described by Dr. J. G Wagner (UK) and Dr. K.T.Rajan (UK). The extremely small amounts of asbestos in the general air. even in urban areas (of the order of 10 nanograms/m3 require EM analysis of the dust collected from samples of 1,000 m1 or more. Dr. S. Holmes (UK) and Dr. W. J. Nicholson (USA) teported remits using this approach. Drs. A. Morgan (UK) and I.. i. Cratlcy (USA) reported on the chromium, cobalt, iron, manganese, nickel, and scandium content of the UICC, and other, asbestos samples; also studies of the solubility of the principal types of asbestos. Chrysotile loses magnesium from the crystal lattice In vivo. Ths biological Importance of this requires further study. The group was not concerned with the setting of environmental standards as such, but with assessing the biological evidence used as part of the information for such standards. Mr. G. W. Gibbs (Canada) and Dr. R. S. J. DuToit (South Africa) reviewed the information about past and present dustiness In the mines and mills where chrysotile and the amphlbolcs were obtained In Canada and South Africa. Mr. G. Berry (UK) discussed the theoretical basis of standards. (Continued on page 4) Belmont) presented his analysis of the puzzling phenomenon of concomitant immunity and examined the role of the diverse components of the Immune response Involved in destroying tumors; the possibility of great variations existing on the function of these components In different anatomical sites was also raised. Other aspects discussed in this connection were the Interplay between lymphocytes and macro phages, the existence of factors released by lymphocytes and, among the latter, the socalled macrophage-arming factor. The role of adjuvant Immunotherapy of metastasis with BCG was most cleirly explained by R. W. Baldwin (University of Nottlnghsm). Employing tumors of different immuno- geniclty. he was able to demonstrate that, when BCG was In close contact with the'tumor celts, it could suppress the growth of metastases, providing the cells possessed sufficient immuno- geniclty. An Interesting report on his clinical experience with Immunoiherapcullc approaches was given by G. HamUton Fairley (Chester Beatty Research Institute, ndmont). In the second part of the program, dealing with the efTects of drugs, the action of poly electrolytes In reducing the spread of cancer was the subject of several papers. Although some of these compounds show a remarkable potency in certain systems and tliclr structureactivity relationship is becoming somewhat clearer, no adequate explanation of their possible mechanism of action has yet been offered. Among the polymers discussed, there Is a group of compounds developed and tested by S. Garattlnl and his co-workers ("Mario Negri" Institute for Pharmacological Research, Milan), which appear to be of special interest, since they do not seem to affect the primary tumot but exhibit considerable potency in reducing cancer-cell dissemination and metastasis. While this work has, so far been only experimental. It does have potential clinical implications. A. Goldin (National Cancer Institute, Bethcsda), in raising Ihe crucial question of whethet cytotoxic agents are less activo In advanced tumors than they are during Ihe early phase of (he malignancy, concluded that the answer was unfortunately positive. He presented several possiblities to explain this reduced drug effectiveness and described certain procedures employed lo counter-act this phenomenon. Another group of compounds, blsdloxlpb perar.inca, described by K. Heilman (Imperial Cancer Research Fund, London), served as a good example of the many agents used lo Interfere with cancer dissemination. It appears that the antltumoral effect of these drugs derives from Uielr ability to normalize tumor vascularization which Impedes the formation of metastases. - In conclusion, It may be said that, although a great deal of further research must be carried out in this complex area, where so many factors interact, the findings presented in this symposium ofTer a new approach to Ihe treatment of cancer, namely a selective therapy of tumor dissemination and metastasis, a problem which has been largely neglected until now. ,<_i/muuicu jtvnt page JJ t Since 19M new prospective mortality <U>d>ct h3Ve shown that (here in Important differences In cancer risks in different parts of the industry. The differences seem to he related to the type of fibre, part dustiness, and other factors. Separation of occupational factors (which probably include, the actual dose of longer but respirable fibre) from that due to (he type of fibre itself has not yet been fully achieved. Populations exposed to only one type of fibre have been largely limited to those in the mines and mills where the mineral is extracted from the rock. With the notable exception of the chrysolite mines In Quebec and possibly those in Italy and Finland, the records elsewhere are not good enough to define populations for strict comparative prospective mortality studies. Information from (he large chrysotile mines in the USSR was not available. Dr. i. C. McDonald (Canada) showed (hat for the chrysotile miners and millers in Quebec, the excess lung and gastro-intcstinal tract cancer risk was small. The link with pleural mesotheliomas was weak, snd there was no evidence of peritoneal tumours. However, the excess lung and gastro-tntertlnal tract tumours war dose-related and restricted to those with the longest snd heaviest exposure. These findings contrast strikingly with the very marked excess of lung and mcsothelial tumours in workers manufacturing and applying insulation materials reported by Dr. IJ. Sclikoff (USA), Dr. M. L. Newhouse (UK) and others. Hie groups studied had all be exposed to more than ono type of fibre. The small amounts of crocidollte used in Insulation work In ihe USA until recently make It very unlikely that the much higher risk In the insulation workers as a group is caused only by croddolite. A group of workers only exposed to amosite, studied by Dr. I. 1. Sclikoff (USA) showed an excess risk of cancers comparable to that of the Insulation workers exposed to both amosite, and chrysotile. These results might be interpreted, when taken in conjunction with the findings In Quebec, as indicating that Ihe risk due to chrysotile is small and that amosite was primarily respon sible for Ihe excess risk in the insulation workers. However, records of the relative amounts of chrysotile and amosite used many years ago in the insulation workers in USA make this hypothesis unlikely. Evidence from the surveillance of amosite miners and millers in South Africa indicates that the excess cancer and mesothelioma risk is much less than in those mining crocidolitc (Dr. I. Webster, South Africa). 'Iherc ate still opportunities to sharpen the compaiiaons between the experience of chrysolite textile, and mine and mill workers from existing records, including information about the iclative dustiness and the type of dust to which Ihese groups have been exposed. Hie followup of those exposed only to crocklnlite lit industry inay add to Ihe evidence linking exposure to crocidolitc and mesotheliomas (Dr. J. S. P. Jones, UK). Dr. M. L. Newhouse (UK) showed that in manufac turing process's, where exposures have been to chrysotile, amosite, and croddolite, the risk of lung cancer and mesothelioma was dose-related. This and other evidence show that there are occupational sub-groups where exposure has been very high compared to that of the general public but where no excess cancer risk has been detected after 20 years. Further follow-ups will be required to measure the full extent of the risk, if any, in these groups. Dr. P.E. Entcrllne (USA) repotted that the mortality from lung cancer was greater In retired asbestos cement workers if they had been exposed to croddolite and chrysolite, than to chrysolite atone. Dr. F.D. Foolvy had examined king tissue from over 100 rases of mesothdiuma, from foul countries, by EM and other methods. When compared with tumoui-frcc lung (Issue, the mesothclioma-bcaring tissue contained more asbestos and amphiboles. Not all mesotheliomas can be related to past exposure to asbestos. Dr. H. T. Plantcydt (The Netherlands) reported urban/rural differences in incidence of mesotheliomas, Ihe reasons for which are not yet dear. Dr. II. C. Hammond (USA) stressed the Importance of recoguir.ing that many factors were probably concerned In Increasing the cancer ri<k. The enhancement of the lungcancer risk by cigarette smoking was great. In L Vne riunbn Internationale sur les effets Hohgiques el Vactivn carcinogine de Vasbeste a eu lieu en octobre dernier ou CIRC, i Lyon. Les participants, qul venaient de 20pays, on! igatement itudii la mise en pratique des recommendations formuiies en 1964 par Ic Croupe de travail de I'UICC sur Vasbeste et te cancer. La rtunhn a porti sur les cinq themes snirants: I) Evaluation critique des mitliodes utilises pour dccclcr, mesurer el etudier les effets de Vasbeste sur Vhomme et les anlmaux. 2) Diffinncct ipldimiobgiqucs du risque d'ashestose et de cancers du poumoit, de la pltrre, dn piritoine, etc., scion la profession, le type de fibres d'ashcsle et d'autres facleurs. 3) Crtrviti et Importance des dipdts d'asbeste dans les ponmons dies les travoillairs exposls ft dens lit population en giniral. J/ Modes possibles d'induction tumorale par I'asbcste. 1) Emploi de Vasbeste dans la collectlvili et utlliti de Vanalyse codts-binifices des Indices sanftaires, sociaux, ironomlques et de sicuriti. Clnquante communications portanl surccs thimes genentu.xont eteprisentfes. Lariunion a mis en Evidence les progres riatisis dans ce domaine au cours des dix derniires anniet et Vimportance des activitis actnellet de recherche Internationale tar les problcmcs senltnires posit par Vasbeste. non-smokers Ihe risk of death from asbestodt exceeded that of lung cancer. Several surveys of asbestos workers had* now shown an excess of gastro-inlcstlnal cancers: though lower than Ihe lung cancer excess, it wst now well enough established to require detailed study. Dr. M. Crecnburg (UK) described the conprthenslve prospective survey of all asbestoa workers now in operation in the UK. Dt. J.C Wagrret (UK), Dr. M. Stanton (USA) and Dr. V. Timbrell (UK) reviewed animal experimental and other evidence on the mechanism of induction of mesotheliomas. The diameter and length of fibre may be critically Important In these tumours in the pleura. Fibres of materials quite different from asbestos have been shown to produce pleural mesotheliomas, but only if they are In such t form that the fibre is comparable in size to that of asbestos. Dr. J. S. Ilarington (SA) reviewed the evidence that chemical factors of asbestos Itself, or metal contamination, or absorbed hydrocarbons' might be important factors In tumour induction. Their importance cannot be excluded particularly bt the light of the synergistic action between cigarette tmoking and asbestos in the production of lung carcinomas, but neither the experimental nor the epidemiological evidence at present has produced strong clues indicating the importance of a definable chemical factor. Cell toxicity of asbestos was reviewed by Dr. A. C. Allison (UK). The information so far appears to be more relevant to an understanding of the flbrogenlcity than of the carcinogenicity of asbestos. Dr. P. C. EJmes (UK) reviewed the natural history of mesotheliomas; treatment hr entirely palliative at present. Immunological methods for the detection of fibrosis [Dr. M. Turner Warwick (UK)] and mesotheliomas [Dr. J. S.P. Jones (UK)] are being intensively studied. The uses and irreplaceapility of asbestos for some purposes were reviewed by Dr. K. N. Undcl! (Canada). Mr. R. Akchurst (UK) outlined Ihe type of information needed from Industry and from medical services to carry out cost/bencfit analyses. It was clear from the meeting, which was attended by representatives of Industry, that there is extensive international research into all aspects of asbestos health problems. Much progress has been achieved In the last 10 years. Possible clues as to how fibres may induca malignancy provide a challenge to design critical experiments to discover the mechanisms concerned. The action being takch to apply the results of new knowledge wat not part of the programme but the need to do to wat emphasized by many speakers. The Proceedings of the Conference and the Recommendations of the Advisory Committee to Use IARC, which met subsequently, will be published shortly, and will provide a most valuable, authoritative international review of the asbestos cancer problem, and show where further research is most needed. - .. U pasado met de oentbre se ha celebrado en cl CIRC fLyint) two minion internacioiwl sober lot cfcclos bhldgicos y la accion carchtdgena del amlanto. Los participantes, proccdcutes de relate paises, se ocuparon asimismo de la puesta en prictica de las rrcnmendacionet formuladas en 1964 por el Grupo de Trabajo de la UJCC sobre Cinceres Asbestdsicos. tat reunbn versh sobre lot cbsco remas siguientet: l) Evatuaehn critica de lot milodns usados para detector, medir y estudlar lot efectos del amlanto en el hombre y en hs animates. 2) Dlferemias epidemioligiens del riesgo de ashestosit y de cinceres de pulmdn, plain, perltoneo. etc. en rtui Urn con la profeshn. el lipo de flbras de amlanto y otros (actons. 3) Grnrrdad e Importcncia Jc las depdsilos pulmonans de amlanto en hs trabe/adorcs expuestos y err la poblacion general. 4) Postbles mecanismot carcinogeniticos del amlanto. S) Empleo del amianto en la cotcctividad y utiUdad del anilisis cxistor-hmcflchs de hs fndices sanitarhs, socintes, economises y ,!; scguridJiI. i'o.W c*tos tanas generates se presentaron clncuenlo trabolot. /-rr reunidn puso de relieve hs programs realizados en la materia durante lot tiltiinos diet ados y la Imporlancla de las cxtuales actividadc: de Invcstlgadin Inlemeclonal sobre lot probkmas tanllarlos planrcatlos por el amianto. Attention: TNM System Fascicle enclosed contains the revised Classifications of malignant tumours fer Breast, Larynx, Stomach, Cervix and Corpus Uteri. Please insert in your TNM Pocket* book*. *" The 2nd. revised Edition of the Pocket-book -- to be available shortly front this Office -- will incoiporate the above-mentioned Classifications.