Document 85qx3QZ797R2Bom0NGwq7qVro

INSTITUTE OF OCCUPATIONAL ANT) ENVIRONMENTAL HEALTH SUITE 'MU 3 PLACE VIIXE MARIE M OXTIIEAX. ua, CA2fAI5A TjO1** TEIXPIIONB ISK) llTIj-ri'S.'MJ January 12, 1973 * To Member-Companies of the Quebec* Asbestos Mining Association Gentlemen: Following the Conference on the Biological Kffeet's of Asbestos in Lyon, October 1972, an Advisory Committee kept working in three panels and eventually presented to the International Agency for Research on Cancer CIARC) its Report and Recommendations for further Research. Some time ago we sent you two yellow books (Volume I. and Volume XI.) of preprints of the Conference on the Biological Effects of Asbestos, in which the first drafts of the recommendations of the three panels, as were then available, were enclosed. Today we present to you, as Volume III. of the Conference, the final Report and revised final Recommendations of the Advisory Committee and its three panels. It is a very interesting and important material. The comments made under "General Review" on pages 4-5 show a valuable change in the international scientific opinion toward seeing the asbestos cancer problem in correct perspective. No doubt the studies supported by our Institute contributed to this change. Sincerely, PVP/st Premysl V. Pelnar, M.D. Scientific Secretary m >w>4 v*' ***** aiV7v;tn/u'i/vCiiv^vC* **v\ 0/V CAA'Ciilt The meeting was held at the International Agency for Research on Cancer Lyon, Franco on 5th and 6th October, 1972. The Coramittco consisted or three panels - Epidemiology, Pathology* Physics and Chemistry. Epidemiology Panel Dr. M. Bcckloke McGill University, Department of Epidemiology * |ie.-,ltl 3775 University Street, Montreal 110, Quebec, Canada. Dr. It. Bohlio . Dr. N. Day Chofarzt dor Strahlcnabtcilung dos Stadtischcn, Krcnkehhauscs Ludcnschcid, 500 Ludcnscheid, Germany Unit of Epidemiology and Biostatistics, International Agency for Research on Cancer, lpO Cours Albert Vhoma; 69008, Lyon, Franco. Prof. P. C. Elmos Department of Therapeutics and Pharmacology, Queen's University of Belfast! Institute of Clinical Science, Grosvenor Road, Belfast, BT12 6J, N. Ireland, UK. */r. v. o, Gxison Medical Research Council, Pneumoconiosis Unit, Llandoi Hospital, Penarth, Glamorgan, Wales, UK. (Chairman) . Dr. J. Lepoutro Medical Department, N.V. Etomit, Kapcllc-op-don-Dos, Belgium*. Prof. J. C. McDonald McGill University, Department of Epidemiology & Healt 3775 University Street, Montreal 110, Quebec, Canada. Mr. C. E. Rossitcr Medical Roscaixh Council, Pneumoconiosis Uiiit, LIando Hospital, Penarth, Glamorgan, Wales, UK. Dr. H. Sakabe Department of Industrial Physiology, Ministry of Labo National Institute of Industrial Health, 2051 Kiseukisumioyofhi-Cho, Knvnsaki, Japan. * Dr. I. J. Selikoff Department of Medicine, Mount Sinai School of Medieij Fifth Avenue and 100th Street, New York, N.Y. 10029, Di*. G.1C. Sluis-Cremer " South African Medical Research Council, National Rest Institute for Occupational Diseases, P.0. Box 4780, Johannesburg, S. Africa. " Dr. V. Smitlior *. Cape Asbestos Co. Ltd., Il4 Park Street, London WIY ; England, UK. - Dr. G. Wright Division of Medicine, St. Luke's Hospital, 113^1 Boulevard, Cluvoland, Ohio 44101, USA. Uitalilf* to ntlrnd Dr. A. C. Allison Clinical Research Centre, Watford Hoad, Harrow Middlesex, IIA1 3UJ, UK. * Mr. G. Berry Medical Research Council, Pneumoconiosis Unit, Llandou Hospital, Ponarth, Glamorgan, Wales, UK. Dr. P. BogoYski Unit of Environmental Carcinogens, International /.goner for Research on Cancer, 250 Cours Albert Thomas, 69,108 Lyon, l')~iUcCv Dr. M. Karin orstein , Pathology Department, Barncrt Memorial Hospital Centre 60 Broadway, Paterson, N.J. 07516, USA Prof. W.T.E.McCaughcy School of Patholoyy, Trinity College, University of Dublin, Dublin 2, Eiro. Prof. D. Magner Canadian Tumour Reference Centre, Department of Pathology, University of Ottawa, Ottawa, Ontario, KIN 6N5, Canada. Prof. H. Otto Dircckior des Pathologischen Institute dor Sladt Krankcnanstalten Bcurhausstrase 60, 66 Dortmund, W. Germany. ' Dr. II. T. Planteydt Dr. M. Stanton Stichting StrccklnboratoriumZccland", Noorcipoortplcin Middelburg, Netherlands. Department of Health, Education and Welfare, National Institute of Health, Bothcsda, MD 20016, USA. Dr. J; C. Wagner Medical Research Council, Pneumoconiosis Unit, Llandc.u* Hospital, Pcnarth, Glamorgan, Wales, UK. (Chairman) ' Prof. S. Watanabe Department of Pathology, National Cancer Centre, Resea: Institute, Tsukigi, 5-1-1, CJiuoku, Tokyo, Japan. Prof. X. Webster Medical Research Council South Africa, National Rosear* Ixistitute for Occupational Diseases, P.0. Box 6788, Johannesburg, South Africa. PJiysics and Chemistry Panel Dr. L. Le Bouffant 1Laboratoire du Centre D'Etudcs et Rccherchcs des Charbonnagcs de France, Verneuill-cn-Hallattc, BP No.2` 60 - Crcil, France. Mr. G. V. Gibbs McGill University, Department of Epidemiology & Health 3775 University Street, Montreal 130, Qacbec, Canada. Dr. S. Jtolmca Asbestos!s Research Council, c/o Turner Bros. Asbestos Co. Ltd. P.0. Box 60, Rochdale, England, UK. Mr. A. Morgan Atomic Energy Research Estab) ir.lunont, Health Fhysics aMedical Division, Building 366, Harwell, Berks., England, UK. Vft *"' Jjt iTjOidy Z>r S Spoil Dr. V. Timbrel1 Dr* R. du Toit Kr. V. H. Volton of S. Vales and Monwouthshiro, Newport Road, Cardiff*, Vales, UC. ' Johns Kar.villo Research and Engineering Centro, P.0* 259, Manville, New Jersey, USA. Medical Research Council, Pneumoconiosis Unit, Llando Hospital, Penarth, Cl amorpan. Vales, UJC. Government Mining Engineer's Division, Department of Mines, P.0. Box 1132, Johannesburg, South Africa.* Institute of Occupational Medicine, Roxburgh Place, Edinburgh EH 0 $SU, Scotland, UK. (Chairman} Tho panels met in a separate session and at the final session (Chairman Dr. . Gilson) prepared this report to tho Director of tho International Agency for Uesca on Cancer* ' * ' TERMS OP REFERENCE . 1- The. Cowmittoo was to report on the present cvidcnco relating exposuro to asbestos dust to cancers, especially that obtained since tho mooting of tho UICC Working Group on Asbestos Cancers in 1964. 2. The Committee was to make recommendations for further research and indicate priorities for work of immediate and long-term value. CO-ORDINATION OP INTERNATIONAL CO-OPERATION * Following tho meeting of the UICC Working Group on Asbestos and Cancers in 1964, a Sub-Committee of the UICC Commission on Geographical Pathology and Environmental Carcinogens (Chairman^ Dr. J. Higginson) was formed to co-ordinate work required to achieve the recommendations. ^ the - In April 1970 agreements between tho UICC and/lARC led to the winding up of tho UICC Sub-Couimittcc and the IARC talcing on responsibility for the Sub committee's work n.nd extending it by supporting certain projects on asbostos cancers in several countries. The Agency has done this as part of their wider programme of investigating environmental carcinogens. Common memberships between uj-uv auij- .umuUuLee uu oC policy. uv*vidJ.uy Cue xiu\Ct<e^ure<2 CuixtipUAC In October 1972 the IARC held an international Conference vitb 137 participants from 20 countries to review all the evidence relatino asbestos with cancers. Subsequently the Advisory Committee prepared its report. This is divided into two sections. First > a general review in the form of answers to a mimber of iwjjortant General questions about the relation of asbestos to cancers of different sites and, secondly, recommendations for further research. GENERAL REVIEW . ' 1. Aro all major commercial types of asbestos ablo to cause luno carcinoma? Yes. Sinco 1964 tho evidence of a causal relationship lias been increased by epidemiological studies showing exposuro-responso relations'for the incidence of lung carcinomas. Tho production of luno carcinomas in cex-tain animals by all 9 types of asbestos supports this conclusion. Tho epidemiological evidence in man, however, shows that xhcro are cl oar differences in x*isk with type of fibre and- nature of exposure. . ' 2. Is there evidence of an increased risk of lung carcinoma at low levels of exposuro to asbostos, such as have been encountered by tho general population in urban areas? . The evidence of an exposuro-responso relationship based in port on past dust measurements and in part on the type of job within tho industry suggests that an excess lung carcinoma risk is not detectablo when the occupational exposure has been low. These low occupational exposures have almost certainly been much greater than that to the public from general air pollution. . 3. Since 196'i has the evidence relating past exposuro to asbestos and mesotheliomas changed? ** Tho cvidonce.-has been greatly strengthened by further prospective, and retrospective mortality studies in many countries of populations exposed to ashes** There is evidence that all commercial types of asbestos except anthophyll Jte way b responsiua.s* iWiueuce jcox c*,* C.cL**t- *41 *a3A 4*i CL.*. % cJjTGi*. w*.. -- v>. . occupations and vith tho typo of asbestos baa increased. The risk is greatest vith crocidolito, less with amosito and apparently less with chrysotilc. With anosite and chrysotilc thero appears to bo a higher risk in manufacturing than in mining and milling. There is also evidence from population studies tliat a proportion of eases of mesothelioma have no known association with exposure to asbestos. * 4. Is there evidonce of an increased risk'of mesothelial cancers at low levels of exposure to asbestos, such os have been encountered by the general population in urban areas? ' . There is evidence of an association' of mesothelial tumours with air pollution in the neighbourhood of crocidolito mines and of factories union ................. mixtures of asbestos fibre types. The evidence relates to conditions many - years aoe. There is evidence of no excess risk of mesotheliomas from asbestos air pollution which has existed in tho neighbourhood of chrysotilc and amosite mines. Thero are reported differences on incidence of mesothelioma between urban and rural areas, the causes of which have not been established. Thero is no evidence of a risk to the general public at present. 5 Since 1964 has'the ovidence changed on the importance of other factors such as cigarette smoking, waxes, oils and trace elements as cor.!-. y factors to the cancer risks? Tho evidenco has accumulated indicating: (1) Cigarette smoking is an important factor enhancing the lung carcinoma risk in asbestos-exposed workers., in both men and women. .Asbestos workers Iiavo specially strong grounds for giving up smoking to protect thoir health. No association has boon demonstrated between 'cigarette smoking and mesotheliomas. (2) Animal experiments designed thus far to test tho importance of waxes and oils as contributory factors in tho production of -*6 - mesothelioma have shown these contaminants aro unlikely to ' bo relevant* ' O) From animal experiments there are no good clues suggesting that trace elements are likely to be a major factor in the production of asbestos cancers.' 6. Vhut other types of cancer are related to exposure to asbcstos7 * Prospective surveys of occupational groups exposed to asbestos Jiavc in general shown a small excess risk of some other types of cancers (in addition to bronchial and mcsothelial), especially those of tbo gaatro-intostinal tract. The excess of these tumours is relatively small compared with that for bronchial cancer. Evidence for an association with ovarian tumours ha3 not been supported by the first largo mortality survey of women previously exposed to asbestos. 7. Is there evidence of an increased risk of cancer' resulting from asbestos fibres present in water, beverages, food or in the fluids used for the administration of drugs7 Such evidence as there is does not indicate any risk. 8. Is there evidence of a risk of lung fibrosis from low levels of exposure to asbestos such as have been encountered by the general population in urban areas? There is at prosent' no evidence of lung damage by asbestos to the general public. The amount of asbestos in the lungs of members of the general public is very small, compared to thoso occupationally exposed. It is greatest where asbestos is mined or worked and lowest in rural areas. 9. Has the relationship between asbestos exposure and the development of pleural plaques been established? Pleural plnqucs hove been associated with past exposure to all commercial types of asbestos.' But additional fnctors, other than asbestos itself, arc involved. The plaques may remain fibrous or become calcified. Not all pleural plficju*'*** ****** with A AAAnAO A A AA UBco>iKEKTUTro?:s von rtmTiinn reseakcu Projects which the Panels rated high in priority are marked ; those which will require close co-operation between the Panels ore marked / . , EPIDEMIOLOGY t The Panel agreed that asbestos related cancers occur in several sites ' in the body. The incidence of the different cancers varies villi a number'of 4. definable factors and for other reasons, such as competing causes of death. . Epidemiological studies will usually provide information on more than one type of cancer. Research directed at only a single type may, on occasions, bo useful but in general the inevitable uncertainties, in some coses in the differential diagnosis of, for example, peripheral lung carcinomas and pleural mesotheliomas, and between peritoneal mesotheliomas and other intra-abdominal # * cancers will require that more than one type is studied at the same time. The Panel recognised that some of the epidemiological projects could only be pursued if there was close co-operation between epidemiologists, pathologists, physicists and chemists, and others, because their success will depend upon the development of improved techniques, some of which ore referred to in the recommendations of the other two Panels. PROJECTS (l) Further development of objective methods for early detection and surveillance of effects caused by asbestos. Topics for particular study include : (a) Immunological techniques for screening.for fibrosis .. and neoplasia. \ ' (b) Functional tests of changes in the peripheral airways. (c) Detection of pleural thickening. - (d) Assessment of the specificity of small irregular opacities in the chest radiograph as defined in the ILO V/C  Co) Testa of tlic usefulness of different techniques of chest radiography, including the use of 100 mm films. ' (f) Development of statistical procedures for analysis and .presentation of serial observations. / (2) Evaluation of the usefulness of early detection in the prevention of progressive fibrosis and asbestos concern, also in the identification of a hazardous conditions. Routine health surveillance of industrial populations * should should be designed to assist epidemiological studies and/include measurement and recording of environmental dust levels. Surveillance of nev entrants couJd be particularly valuable. Arrangements should be made to register vorkors so that theirrorbidity and mortality experience can bo studied even after cessation of exposure to asbestos. ' *. O) Assessment of excess cancer risks following exposure to only one type of fibre. * (a) Chrysotile: The much higher cancer rislc reported for chrysotile textile workers compared with mine and mill workers requires explanation. How much is explicable by differences in siv.e of past airborne fibres and/dustiness? There is need to make more use of past dust records for relating to indices of disease. (b) Amosite: The excess lung carcinoma and mesothelioma risk is - apparently much greater in the manufacturing and application ' sections of the industry than in the mining and milling of this type of fibre. What'-.ore the important factors in this reported difference? (c) Crocidolitc; Further studies are required in occupational groups exposed only to crocidolite or umositc or chrysotile in the manufacturing and application parts of the industry to establish more clearly differences in risks due to different fibres.  / (/i) Studios of the amount and type of asbestos in the Jungs of cases of # mesotheliomas (if possible by cell type) in (a) national survey of mesotheliomas, (b) representative samples of ensos' arising in croups with a definable past exposure. (5) Studies of secular changes in incidence of pleural and peritoneal mesotheliomas nationally and internationally. (6) Epidemiological studies to investigate the association between past exposure to asbestos and cancer of sites other than lung, pleura, and peritoneum. * (7) Studies of secular trends in the asbestos content of the lungs in the general population. / (0) Studies to relate amount and type of asbestos in the lung and estimates of past dust exposure and interval since last exposure. (9) Experimental.and epidemiological studies-to investigate possible differences of effect of continuous low and intermittent high exposure to asbestos. ' ' (10) Opportunities afforded by intercurrent deaths should be used to interrelate radiographic appearances, lung pathology, respiratory function, dust content, and type in asbestos workers. Standardised techniques and classification recommended by the Panels should be used. . . (ll) Investigate the prognostic significance and aetiological factors in the development of calcified and uncalcified pleural plaques in different environments. . (12) Investigate tale-exposed groups in mining and manufacturing to establish any differences In morbidity or mortality which might be related to the amount and shape of the ^inc respirable particles. (13) Development of cost/boncfit analyses to study the health, safety, social and economic interrelations of the use of asbestos. -iO- ' . PATHOLOGY AMD EXPERIrjnXTAL PATltOIflGY * - The Panel reviewed t)c progress made on the 39^ UICC reconuncjid.it ions. It was agreed that considerable progress had .been miidc on the majority of the recommendations. Some require further study, or modification of previous methods of investigation; these are included in the list of recommendations that follows. The recommendations are divided into three categories, morbid anatomy and histology, clinical research, and experimental studies. .. , PROJECTS Morbid Anatomy and Histology 1. Asbestosis . (l) Further consideration should be given to methods for determining the amounts, types and structural features of asbestos in tissue. A Sub committee should be established with members of the Physics and Chemistry * Panel, and others to accelerate vor)c on this problem. (2) The methods for assessing the severity of asbestosis (see paper 9) should be tested for consistency by different observers. 2. Carcinoma / (l) An investigation of whether reduction of asbestos exposure to levels below those producing asbestosis also abolishes excess risk of _ carcinoma was considered important. (2) A comparison of lung carcinomas in persons occupationally exposed to asbestos and those not so exposed, including both cigarette smokers and non-smokers, in respect of sites of origin and cytology of tumours and presence or absence of asbestosis, would be of value. ' w*n a Anri 3* fiot iamnn , (1) TJic'InlornntioH.'ii Piuicl of Pathologists1 am! National paMols *2 established following the 196^ meeting have served n useful purpose. It it* recommended that panels be established in other countries and membership of the International Panel be expended* The main purposes of these Psmels is to ensure uniformity of diagnostic criteria and recording of histological typos of diffuse mesotheliomas. Collaborative study of histology slides in National Panels is recommended. Tho diagnosis of mesothelioma can be mode by exfoliative cytology of the pleural fluid. If the cytoloyical diagnosis is made by a competent cytologist, biopsy may be unnecessary. (2) To improve consistency of diagnosis there is an urgent need for a Comprehensive Atlas on mesotheliomas, or alternatively, for inclusion of an enlarged section on mesotheliomas in the new edition of the VHO Monograph on Tumours of the Lung. Criteria for diagnosis by exfoliative cytology and a description of the fine structure of mesotheliomas should bo included. Clinical Research ' * / (l) Monitoring by immunological, methods of populations exposed to asbestos should be investigated to ascertain whether it is possible to recognize those who arc developing, or will develop, tumours. (2) Tho use of chromatographic methods for the study of wucopolysnccberid' and other tumour-associated substances in pleural fluids should be explored. Sensitive methods might be developed and applied to identify secretory products of mesotheliomas in blood and urine. The International Panel consists of: Dr. H. Kanncrstcin (ISA), Prof. D. Kagner (Canada), Dr. L. Mcununn (Finland), Prof. V.T.E. McCnughey (Eire), Prof. II. Otto (FRG), Dr. H. T. Plnntcydt (K'o.thnrlmids), Dr. E, Roitzuch, (GDR), Prof. L. Santi (Italy), Prof. I. Vcbstor (South Africa), and Dr. J.C.Vagncr (UK) as Secretary. 2 .. Great Britain, South Africa, United States, Canada, Netherlands. Further Experimental Studies (l) Information is required about the role of fine particles, especially influence of fibre sisto, in the induction of tumours. Those studies should be extended to include fibres other than asbestos. A Sub-Committee should bo established to review the need for, and arrange the distribution of standard samples of asbestos and other fibres in addition to the UICC Reference Samples. ^ / (2) The fate of inhaled particles of various sizes, shapes and chemical compositions, should be studied to determine, moro precisely the quantities and sites of initial deposition, change within the body and later retention. The feasibility of increasing fibre elimination by various methods should be explored. Studies should be made of moan3 of reducing the fibrogcnicity and carcinogenicity of fibres already retained in the lungs. t (3) The use of 'cell and organ culture, including mesothelial tissue from man and other species, should be further .investigated with a view to developing methods of screening dusts for fibrogenic and cnrcinoocnic properties. (4) Further studies should be carried out to determine the nature of the combined effect on tumour induction when animals arc exposed to asbestos dust and cigarette smoke, metals or other chemical carcinogens, including those which act systemically such as nitrosarainos. (5) Inhalation experiments should be extended to test various types of fibre; of special interest ore forms of chrysotlle and erocidolite including the finer grade materials. (6) It was felt that studies of the pathological effects of asbestos on species other than rodents would be of value. (7) The effect of long-term ingestion of fibres of various sizes, shapes and chemical compositions should be studied. > . (8) The Effects of fibres and associated metals on the metabolism of target organs should be investigated. PHYSICS AND cmnsrnY Tho Panel reviewed the progress made on the 1964 UICC Recommendations proposals for the preparation and characterisation of the UICC reference sampl of asbestos had been satisfactorily implemented', and tho Panel recommended tlwit a list of references to papors featuring the samples should be distributed to investigators in-this field. Considerable progress had boon made on methods of identifying the type of fibre in tissues but a quantitative method when several types of fibres were present had yet to be developed. The Panel discussed the further .contribution that physical and chemical studies can make to research on the biological effects of asbestos and other fibrous materials. Of especial interest arc tho effects of fibro siy.c and shape on the retention of material in the lungs, tho site of deposition, the migration of fibres within tho body, and their carcinogenic or other biological activity. Tho following recommendations wero made: PROJECTS 1. Materials for experimental work a) Supplies of asbestos from relevant sources should be obtained where thero is evidence of variation in geological form, trace element content or significant biological findings. . b) Small samples of various fibrous materials should be prepared for studies on the influence* of fibre size and shape on carcinogenicity. For this purpose the samples should be milled to different degrees of fineness. c) For investigations on the influence of particle shape and size, on the inhalation and subsequent fate of asbestos fibres a chrysotilo and an amphibolc of fibre length greater than the UICC samples should be prepared. 2. Methods . a) There in an urgent need for the quantitative assessment, size analysis and characterization of particles and fibres in tho lungs and other organs. Details f available methods should bo circulated, international comparison:: 1'f- b).Ho methods are nt present available for the preparation'of fibres in narrow ranges of diameter and length in sufficient quantities for inoculation experiments. Techniques for these purposes ore urgently required, especially in view of the advantages such graded samples could provide for investigating the influence of these physical, factors on the carcinogenicity of fibres of different materials. - c) Since the degree of dispersion of fibres (especially chrysotile) used in inoculation studies may have' a marked influence on their carcinogenicity, methods are required for quantifying dispersion. d) Inhalation studies require precise control of the characteristics of the dust clouds. Improved methods of dispensing fibrous dusts in such investigations need to be developed. e) Methods are available for collecting the important sixe fractions of dust clouds in inhalation studies when the particles are of compact shape.. Similar methods must be developed for fibrous particles. f) The present membrane filter methods of measuring the levels of airborne asbestos dust require standardization. This should be done by inter-laboratory trials on a continuing basis. Particle counting by electron microscopy should also be developed. Gravimetric assessment methods and the automation of particle counting should be explored. . 3* Inhalation studies ' Considerable information is now.available on the deposition, retention and migration of particles of compact shape. Recently developed methods, especially . . I- . radio-active tracer techniques, should be used to obtain similar knowledge for fibrous particles. This- information is needed to identify the biologically important size fraction and to help interpretation of epidemiological and * ** pathological studies. -35- h. Occupational nnd environmental nturties * ' * . The use of both fibre counts nnd gravimetric methods for assessing asbestos dust concentrations should bo encouraged. Data collected over nn extended period vilJ bo particularly valuable in identifying the parameters of the dust which can be corrcloted with epidemiological evidence on the health hazard. 5. Physics nnd Chemistry Panel It is recommended that an international Panel be established to assist in implementing these recommendations. The Panel would periodically review requirements for materials for experimental work; provide guidance on physical and chemical problems; and arrange national and international standardization trials.