Document rBQxqzd6x9O5mxdoyL4Bn6dgv

HOW TO USE THE8E SEPARATORS Use one page fo r each sep aration . S elect appropriate ta b , add fu r th e r Id en tifica tio n i f d e s ir e d , and co v er it with scotch tape. Cut o f f and d is c a r d al 1 tabs except the one covered by tape. TABBED SEPARATOR SHEET Fora HEM-69B <*-) B rit. J . inclusir. M e d ., 1973, 30, 180-186 ?7f Report of the Advisory Committee on Asbestos Cancers to the Director of the Internationa! Agency for Research on Cancer In 1964 the Geographical Pathology Committee of the International Union against Cancer (UICC) set up a working group on asbestos and cancer and later issued a Report and Recom m endations (1965). A further meeting was held at the International Agency for Research on Cancer (IARC), Lyon, France, on 5 and 6 October 197-. This was organized jointly with the Medical Research Council Pneumoconiosis Research Unit. The report and recommenda tions given here will also be published by IARC in 1973, together with the complete pro ceedings of the meeting. The Committee consisted of three panels--Epidemiology, Pathology, and Physics and Chemistry. T he panels met in separate sessions and at the final session (Chairman Dr. J. C. Gilson) prepared this report to the Director of the International Agency for Research on Cancer. Terms of reference 1. The Committee was to report on the present evidence relating exposure to asbestos dust to cancers, especially that obtained since the meeting of the U ICC W orking G roup 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. in several countries. The Agency has done this as part of their wider programme of investigating environmental carcinogens. Common memberships between the UICC sub-committee and the com mittee advising the IARC ensured continuity of policy. In October 1972 the IARC held an international conference with 137 participants from 20 countries to review all the evidence relating asbestos to cancers. Subsequently the Advisory Committee prepared its report which is divided into two sections, first, a general review in the form of answers to a number of important general questions about the relation of asbestos to cancers of different sites and, secondly, recommendations for further research. Co-ordination of international co-operation Following the meeting o f the UICC Working G roup on Asbestos and Cancers in 1964, a sub committee of the UICC Commission on Geo graphical Pathology and Environmental Carcino gens (Chairman D r. J. Higginson) was formed to co-ordinate work required to achieve the recom mendations. in April 1970 agreements between the UICC and the IARC led to the winding up of the UICC sub-committee and the IARC taking on respon sibility for the sub-committee's work and extending it by supporting certain projects on asbestos cancers General review 1. Are all major commercial types of asbestos able to cause lung carcinoma? Yes. Since 1964 the evidence of a causal rela tionship has been increased by epidemiological studies showing exposure-response relations for the incidence of lung carcinomas. The production of lung carcinomas in certain animals by all types of asbestos supports this conclusion. The epidemio logical evidence m man, however, shows that there arc clear differences in risk with type of fibre and nature of exposure. 180 o f the Advisory Committee on / U t / i ^ _'* 2. Is there evidence of an increased risk o f lung carcinoma at low levels o f exposure to asbestos, such as have been encountered by the general population in urban areas? The evidence of an exposure-response relationship based in part on past dust measurements and in part on the type of job within the industry suggests that an excess lung carcinoma risk is not detectable 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 1964 has the evidence relating past exposure to asbestos and mesotheliomas changed? The evidence has been greatly strengthened by further prospective and retrospective mortality studies in many countries of populations exposed to asbestos. There is evidence that all commercial types o f asbestos except anthophyllite may be responsible. Evidence for an im portant difference in risk in different occupations and with the type of asbestos has increased. The risk is greatest with crocidolite, less with amosite, and apparently less with chrysoiiie. With amosite and chrysotile there appears to be a higher risk in m anufacturing than in mining and milling. There is also evidence from population studies that a proportion of cases of mesothelioma have no known association with exposure to asbestos. 4. Is there evidence o f an increased risk of meso- thelial cancers at low levels of exposure to asbestos, such a s have been encountered by the general population in urban areas? There is evidence o f an association of mesothelial tumours with air pollution in the neigh,bourhood of crocidolite mines and of factories using mixtures of asbestos fibre types. The ev idence relates to con ditions many yeats ago. There is evidence of no excess risk of mesotheliomas from asbestos air pollution which has existed in the neighbourhood of chrysotile and amosite mines. There are reported differences on incidence of mesothelioma between urban and rural areas, the causes of which have not been established. There is no evidence of a risk to the general public at present. 5. Since 1964 has the evidence changed on the importance o f other factors such as cigarette smoking, waxes, oils, and trace elements as con tributory factors to the cancer risk? The evidence has accumulated indicating: (1) Cigarette smoking is an important factor enhancing the lung carcinoma risk in asbestosexposed workers, in both men and women. Asbestos workers have specially strong grounds for giving up smoking to protect their health. No association has been demonstrated between cigarette smoking and mesotheliomas. (2) Animal experiments designed thus far to test the importance of waxes and oils as contributory factors in the production of mesothelioma have shown that these contaminants arc unlikely to be relevant. , (3) 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. What other types of cancer are related to exposure to asbestos? Prospective surveys of occupational groups exposed to asbestos have in general shown a small excess risk of some other types of cancers (in addition to bronchial and mesothelial), especially those of the gastrointestinal tract. The excess of these tumours is relatively small compared with that for bronchial cancer. Evidence for an association with ovarian tumours has not been supported by the first large mortality survey of women previously exposed to asbestos. 7. Is there evidence of an increased risk o f cancer resulting from asbestos fibres present in water, beverages, food or in the fluids used for the ad ministration of drugs? 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 present 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 with the lungs of those 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 plaques have been associated with past exposure to all commercial types of asbestos. But additional factors, other than asbestos itself, are involved. The plaques may remain fibrous or become calcified. Not all pleural plaques are associated with asbestos. Recommendations for further research Projects which the panels rated high in priority are marked *; those which will require close co-opera tion between the Panels are marked f. Epidemiology The panel agreed that asbestos-related cancers occur in several sites in the body. The incidence of the different cancers varies with a number of definable factors and for other reasons, such as competing causes of death. Epidemiological studies will usually 182 Report o f the Advisory Committee on Asbestos Cancers provide information on more than one type of cancer. manufacturing and application sections of the Research directed at only a single type may, on industry than in the mining and milling of this type occasions, be useful, but in general the inevitable of fibre. VVhat are the important factors in this uncertainties, in some cases in the differential reported diil'erence? diagnosis of, for example, peripheral lung car (c) Crocidolite Further studies are required in cinomas and pleural mesotheliomas, and between occupational groups exposed only to crocidolite or peritoneal mesotheliomas and other imra-abdominal amosite or chrysotile in manufacturing and applica cancers, will require that more than one type is tion parts of the industry to establish more clearly studied at the same time. differences in risks due to different fibres. The panel recognized that some of the epidemio (4) *t Studies of the amount and type of asbestos in logical projects could be pursued only if there was the lungs of cases of mesothelioma (if possible by close co-operation between epidemiologists, patholo cell type) in (a) a national survey of mesotheliomas, gists, physicists and chemists, and others, because and (A) representative samples of cases arising in their success will depend upon the development of groups with a definable past exposure. improved techniques, some of which are referred to (5) * Studies of secular changes in the incidence of in the recommendations of the other two panels. pleural and peritoneal mesotheliomas nationally and internationally. Projects (I) 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 o f pleural thickening, (6) * Epidemiological studies to investigate the association between past exposure to asbestos and cancer of sites other than lung, pleura, and peri toneum. (7) Studies of secular trends in the asbestos content of the lungs in the general population. (8) *x Studies to relate amount and type of asbestos in the lung and estimates of past dust exposure and interval since last exposure. (d) assessment of the specificity of small irregular (9) Experimental and epidemiological studies to opacities in the chest radiograph as defined in investigate possible differences of effect of continuous ILO U/C Classification, 1971, low and intermittent high exposure to asbestos. (e) tests of the usefulness of different tech (10) Opportunities afforded by intercurrent deaths niques of chest radiography, including the use of should be used to interrelate radiographic appearan 100 mm films, ces, lung pathology, respiratory function, and dust ( / ) development of statistical procedures for content and type in asbestos workers. Standardized analysis and presentation of serial observations. techniques and classification recommended by the 2) Evaluation o f the usefulness of early detection panels should be used. in the prevention o f progressive fibrosis and asbestos (11) Investigation of the prognostic significance and cancers, also in the identification of hazardous aetiological factors in the development of calcified conditions. Routine health surveillance of industrial and uncalcified pleural plaques in different environ populations should be designed to assist epidemio logical studies and should include measurement and recording of environmental dust levels. Surveillance o f new entrants could be particularly valuable. Arrangements should be made to register workers so that their morbidity and m ctality experience can be studied even after cessation of exposure to asbes tos. (3)* Assessment of excess cancer risks following exposure to only one type of fibre : ments. (12) Investigation of talc-exposed groups in mining and manufacturing to establish any dif ferences in morbidity or mortality which might be related to the amount and shape of the fine respirable particles. (13) Development of cost/benefit analyses to study the health, safety, social, and economic interrelations of the use of asbestos. (a) Chrysolite The much higher cancer risk reported for chrysotile textile workers compared Pathology and experimental pathology with mine and mill workers requires explanation. The panel reviewed the progress made on the 1964 How much is explicable by differences in size of airborne fibres and past dustiness? There is need to make more use of past dust records for relating to indices of disease. U1CC recommendations. It was agreed that con siderable progress had been made on the majority of the recommendations. Some require fun her study, or modification of previous methods of investigation; (A) Amosite The excess lung carcinoma and these are included in the list of recommendations mesothelioma risk is apparently much greater in the that follows. The recommendations are divided into Report o f the Advisory C o m m it^^kn Asbestos Cancers 183 three categories; morbid anatomy and histology, Clinical research clinical research, and experimental studies. (1) *t Monitoring by immunological methods of populations exposed to asbestos should be in Morbid anatomy and histology vestigated to ascertain whether it is possible to Projects recognize those who are developing, or will develop, 1. Asbestosis tumours. (1) * Further consideration should be given to (2) The use of chromatographic methods for the methods for determining the amounts, types, and study of mucopolysaccharides and other tumour- structural features of asbestos in tissue. A sub associated substances in pleural fluids should be committee should be established with members of explored. Sensitive methods might be developed and the Physics and Chemistry Panel and others to applied to identify secretory products of meso accelerate work on this problem. theliomas in blood and urine. (2) The methods for assessing the severity of asbestosis should be tested for consistency by Experimental studies different observers. (1) * Information is required about the role of fine 2. Carcinoma particles, especially the influence of fibre size, in the (1) *f An investigation o f whether reduction of induction of tumours. These studies should be asbestos exposure to levels below those producing extended to include fibres other than asbestos. A asbestosis also abolishes excess risk of carcinoma sub-committee should be established to review the was considered important. need for, and arrange the distribution of, standard (2) A comparison of lung carcinomas in persons samples of asbestos and other fibres in addition to the occupationally exposed to asbestos and those not so UICC reference samples. 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. 3. Mesothelioma (1) The International Panel of Pathologists1 and National Panels established following the 1964 meeting2 have served a useful purpose. It is recom mended that panels be established in other countries and membership of the International Panel be extended. The main purpose of these panels is to ensure uniformity of diagnostic criteria and recording of histological types of diffuse mesothelioma. Col laborative study of histology slides in National Panels is recommended. The diagnosis of meso thelioma can be made by exfoliative cytology of the pleural fluid. If the cytological 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 mesothe liomas or, alternatively, for inclusion of an enlarged section on mesotheliomas in the new edition of the WHO Monograph on Tumours of the Lung. Criteria for diagnosis by exfoliative cytology and a description of the fine structure of mesotheliomas should be included. (2) t The fate of inhaled particles of various sizes, shapes, and chemical compositions should be studied to determine more 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 means of reducing the fibrogenicity and carcinogenicity o f fibres already retained in the lungs. (3) The use of cell and organ culture, including mesothclia! tissue from man and other species, should be further investigated with a view to develop ing methods of screening dusts for fibrogcnic and carcinogenic properties. (4) Further studies should be carried out to determine the nature of the combined effect of tumour induction when, animals are exposed to asbestos dust and cigarette smoke, metals or other chemical carcinogens, including those which act systemically, such as nitrosamines. (5) Inhalation experiments should be extended to test various tv pcs of fibre; of special interest are forms of chrysotilc and crocidolite, 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. (?) The elleel of long-term ingestion of fibres of The International Panel consists of: Dr. M. Knnnerstein (USA), Professor D. Mapper (Canada), Dr. L. M eurim n (Finland). Professor W. T. E. M eCaughey (Eire), Professor It. O tto (I'R G ). Dr. 11. Plantevdi (N ether lands). Dr. E. Roitr.sch (CiDR), Professor L. S.um (ltal>). P iofe ssor I. various sizes, shapes, and chemical compositions should be studied. (8) Effects of fibres and associated metals on metab olism of target organs should be investigated. Webster (South Africa), and Dr. J. C. Wagner (UK.) as Secretary. Physics and chemistry Great Britain, South Africa, United States, Canada, Netherlands. The panel reviewed the progress made on the 1964 184 Report o f the Advisory Committee on Asbestos Cancers UICC Recommendations. The proposals for the preparation and characterization of the UICC reference samples of as! cstos had been satisfactorily implemented, and the panel recommended that a list of references to papers featuring the samples should be distributed to investigators in this field. Considerable progress had been made on methods of identifying the type of fibre in tissues but a quan titative 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 are the effects of fibre size and shape on the retention of material in the lungs, the site of deposition, the migration of fibres within the body, and their carcinogenic or other biological activity. The following recom mendations were made: Projects 1. Materials for experimental work*t (a) Supplies of asbestos from relevant sources should be obtained where there is evidence of varia tion 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 chrysotile and an amphibole of fibre length greater than the UICC samples should be prepared. 2. Methods*t (a) There is an urgent need for the quantitative assessment, size analysis, and characterization of particles and fibres in the lungs and other organs. Details of available methods should be circulated, international comparisons undertaken, methods standardized, and new techniques developed. (b) N o methods are at present available for the preparation of fibres in narrow ranges of diameter and length in sufficient quantities for inoculation experiments. Techniques for these purposes are urgently required, especially in view of the advantages such graded samples could provide for investigating the influence of these physical factors on the carcino genicity of fibres of different materials. (c) Since the degree of dispersion of fibres (es pecially 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. (f) Methods are available for collecting the impor tant size fractions of dust clouds in inhalation studies when the particles are of compact shape. Similar methods must be developed for fibrous particles. (/) The present membrane filter methods of measuring the levels of airborne asbestos dust require standardization. This should be done by intcrlaboratory 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 studiest Considerable information is now available on the deposition, retention, and migration of particles of compact shape. Recently developed methods, especially radioactive tracer techniques, should be used to obtain similar knowledge for fibrous par ticles. This information is needed to identify the biologically important size fraction and to help inter pretation of epidemiological and pathological studies. 4. Occupational and environmental studies The use of both fibre counts and gravimetric methods for assessing asbestos dust concentrations should be encouraged. Data collected over an extended period will be particularly valuable in identifying the parameters of the dust which can be correlated with epidemiological evidence on the health hazard. 5. Physics and chemistry panel It is recommended that an international panel be established to assist in implementing these recom mendations. The panel would periodically review requirements for materials for experimental work, provide guidance on physical and chemical prob lems, and arrange national and international standardization trials. References ILO U/C International Classification of Radiographs of Pneumoconioses 1971. Occupational Safety an d Health Series. International L ab o u r Office, Geneva, 1972. Report and Recommendations ol the Working Group on Asbestos and Cancer convened under the auspices of the Geographical Pathology Committee of the International Union against Cancer (UICC) (1965). British Journal o f Im lu a n a l M a th me, 22, 165-171. Report o f the Advisory Committee on Asbestos Cancers 185 Dr. M. Becklake Dr. H. Bohlig Dr. N. Day Professor P. C. Elmes Dr. J. C. Gilson D. J. Lcpoutre Professor J. C. McDonald Mr. C. E. Rossiter Dr. H. Sakabe Dr. 1. J. SelikofP Dr. G. K. Sluis-Cremer Dr. W. Smither Dr. G. Wright Dr. A. C. Allison Mr. G. Berry Dr. P. Bogovski Dr. M. Kanncrstein ' Professor W. T. E. McCaughey Professer D. Magner Professor H. Otto Dr. H. T. Planteydt Dr. M. Stanton Dr. J. C. Wagner Professor S. W'atanabe Professor I. Webster Dr. L. Lc Bouffant Mr. G. W. Gibbs Dr. S. Holmes Epidemiology panel McGill University, Department of Epidemiology and Health, 3775 University Street, Montreal 110, Quebec, Canada Municipal Hospital Ldenscheid, 588 Ldenscheid, Germany International Agency for Research on Cancer, Unit of Epidemiology and Biostatistics, 150 Cours Albert Thomas, Lyon 69008, France Queen's University of Belfast, Department of Therapeutics and Pharmacology, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK Medical Research Council, Pneumoconiosis Unit, Ltandough Hospital, Penarth, Glamorgan, Wales, UK (Chairman) S.A. Eternit, Medical Department, 2920 Kapelle-op-den-Bos, Belgium McGill University, Department of Epidemiology and Health, 3775 University Street, Montreal 110, Quebec, Canada Medical Research Council, Pneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, Wales, UK Ministry of Labour, Department of Industrial Physiology, National Institute of Industiia! Health, 2051 Kizukisumivoshicho, Kawasaki, Japan Mount Sinai School of Medicine, Environmental Sciences Laboratory, 100th Street and Fifth Avenue, New York, NY 10029. USA South African Medical Research Council. National Research Institute o f Occupational Diseases, PO Box 4788, Johannesburg, South Africa British Asbestos Research Council, 114 Park Street, London W1Y4AB, England, UK Department of Medical Research, St Luke's Hospital, 11311 Shaker Boulevard, Cleveland, Ohio 44101, USA . Pathology panel Medical Research Council, Clinical Research Centre, Watford Road, Harrow Middlesex HA1 3UJ, England, UK Medical Research Council, Pneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, Wales, UK International Agency for Research on Cancer, Unit of Environmental Carcino gens, 150 Cours Albert Thomas, Lyon 69008, France Barnert Memorial Hospital Centre, Pathology Department, 680 Broadway, Paterson, NJ 07514, USA Trinity College School of Pathology, University of Dublin, Dublin 2, Eire Canadian Tumour Reference Centre, Department of Pathology, University of Ottawa, Ottawa, Ontario, KIN 6N5, Canada Direktor des pathologischen Instituts der Stadt Krankenanstalten, Beurhaus- strasse 40, 46 Dortmund, West Germany Stichting Streeklaboratorium "Zeeland", Noorpoortplein 2, Middlcburg, The Netherlands National Institute of Health, Department of Health, Education and Welfare Bethcsda, Md, 20014, USA ' Medical Research Council, Pneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, Wales, UK (Chairman) National Cancer Centre, Research Institute, Department of Pathology, Tsukiji, 5-1-1 Chome, Chuo-ku, Tokyo, Japan Medical Research Council South Africa, National Research Institute for Occupa tional Diseases, PO Box 4788, Johannesburg, South Africa Physics and chemistry panel Centre d'Ftudes et de Recherches des Charbonnages de France, Verneuil-cnHallntte, B.P. No. 27, 60550 Creil, France McGill University, Department of Epidemiology and Health, 3775 University Street, Montreal 110, Quebec, Canada Asbcstosis Research Council, c/o Turner Bros, Asbestos Co. Ltd., PO Box 40, Rochdale. England, UK Unable to attend. 4 186 Report o f the Advisory Committee on Asbestos Cancers Mr. A. Morgan Dr. F. D. Pooley Dr. S. Speil Dr. V. Timbrel! Dr. R. S. J. du Toit Mr. W. H. Walton Atomic Energy Research Establishment. Health Physics and Medical Division, Building 364, Harwell, Didcot, Berks, England, UK University College of South Wales and Monmouthshire, Department of Mineral Exploitation, Newport Road, Cardili, Wales, UK Johns-Manville Research and Engineering Center, Greenwood Plaza, Denver, Colorado, USA Medical Research Council, Pneumoconiosis Unit, Llandough Hospital, Penarth, Glamorgan, Wales, UK Government Mining Engineer's Division, Department of Mines, PO Box 1132, Johannesburg, South Africa Institute of Occupational Medicine, Roxburgh Place, Edinburgh EHS 9SU, Scotland. UK (Chairman) The January (1973) Issue Morbidity of British coal miners in 1961-62 F. D. K. Liddell M ortality of British coal miners in 1961 F. D. K. Liddell A study of the acute and chronic changes in ventilatory capacity of workers in Lancashire cotton mills G. Berry, C. B. McKerrow, M. K. B. Molyneux, C. E. Rossiter, and J. B. L. Tombleson Use of radioisotopes in the study of textile workers with byssinosis and chronic lung damage L. S. Vaskov A survey of respiratory disease in cotton operatives. Part I. Symptoms and ventilation test results A. J. Fox, J. B. L. Tombleson, A. Watt, and A. G. Wilkie A survey of respiratory disease in cotton operatives. P art II. Symptoms, dust estimations, and the effect of smoking habit A. J. Fox, J. B. L. Tombleson, A. W att, and A. G. W ilkie Computer simulation of industrial hazards E. G. Knox Relationship between sickness absence and length of service S. J. Pocock Radiological changes in carpal and meracarpal bones and phalanges caused by chain saw vibration T. Kumlin, M . W iikeri, and P. Sumari Effect of silica on phospholipids in the rat lung M. G rnspan, H. Antweiler, and W. D ehnen Industrial ammonia gassing M. W alton Notes and miscellanea Safety and health at work: The Robens Report R. C. Browne Employment Medical Advisory Service M argaret G racey Book review's Information section A num ber o f copies are still available and may be obtained from the Publishing Manager, British Medical Association, Tavistock Square, London WC1H 9JR, price P25 (F50 in countries overseas; U.S.A. $3.60).