Document KJKmVq8knB9d3BBxO2E0wO9dX

DIRECTOR OK THE INTERNATIONAL AGENCY FOR c-orco c o o o o e o ON CANCER The meeting was held at Die International Agency for Research on 1 Lyon, France on Rtb and 6th October, 1972* The Committee consisted of panels - Epidemiology, Pathology, Physics and Chemistry Epidemiology Panel Dr M. Dccklake McGill University, Department of Epidemiol 3779 University Street, Montreal 110, Quel Dr H Bohlig Chefarzt der Strahlenabteilung des Stndtis Krenkenljaur.es Ludcnschoid, 388 Luden.scheic D r *_ N * Day Unit of Epidemiology and Riostatistics, Ii Agency for Research on Cancer, 130 Cours J 69008. Lyon, France* Prof P. C Elmes Department of Therapeutics and Pharmacolot University of Belfast, Institute of Clinii Grosvcnor Road, Belfast, 33X12 6)3J, N. Ire Dr, J. C. Gilson Medical Research Council, Pneumoconiosis Hospital, Pen'arth, Glamorgan, Vales, UK. Dr J. Lepoutre Medical Department, N.Y, Eternit, Kapelle Belg iu m Prof J. C. McDonald McGill University, Department of Epidcmio 3773 University Street, Montreal 110, Que Mr* C. E e Rossiter Medical Research Council, Pneumoconiosis Hospital, Penartb, Glamorgan-, Vales UK. Dr II. Sakabe Department of Industrial Physiology, Mini National Institute of Industrial Health, 2031 Kizukisumioyoshi-Cho, Kavasaki, Jap; * Dr* I. J. Sclikoff Depai'tr.lent of Medicine, Mount Sinai Scho< Fifth Avenue and 100th Street, New York, Dr* G.K. Sluis-Crcmcr Soutli African Medical Research Council, Institute for Occupational Diseases, P.0 Johannesburg, S. Africa. Dr* V* Sniither Dr G. V/right . Capo. Asbestos Co Ltd. ,.1.l^i Park Street, England, UK* * Division of Medicine, St. Luke's llosp.ita Boulevard, Cleveland, Ohio h h 101, USA. Dr* Ac C. Allison CJ.m i c a i Kcscarcn oun u u ^ Middlesex, 11A1 3UJ, UK* n >.-<.*<.*, **.>.* Mr* G e Berry Medical Research Council, Pneumoconiosis Un Hospital, Pcnarth, Glamorgan, Vales, UK. Dr* P. Bogovski Unit of Environmental Carcinogens, T.ntcrnat for Hesearch on Cancer, 150 Cours Albert Th Lyon, Prance. Dr* M. Kannerstein Pathology Department, Barnert Memorial Hosp 680 Broadway, Pater.son, N.J. 0751^1 USA Pi'of. V.T.E. McCaughey School of Pathology, Trinity College, Univc Dublin, Dublin 2, Dire. Prof* Dc Magner Canadian Tumour Reference Centre, Departmer Pathology, University of Ottawa, Ottawa, Or lvIN 6a'3 , Cana da ,, Prof!* 1!. Otto Dr. H. T* Planteydt Direcktor de.s Pathologischen Jnstituts dor Krankenanstalten Beurbausstrase /jO, kG Dori V/* Germany. v Stichting StrccklaboratoriuinnZccland", Kooi Middelburg, Netherlands. Dr. M* Stanton Department of Health, Education and Vclfan Institute of Health, Dcthesda, MD 2001 h , If Dr* J. C. Vagner Medical Research Council, Pneumoconiosis U; Hospital, Pcnarth, Glamorgan, Vales, IHC. Pr of . S . V atanabe Department of Pathology, National Cancer C Institute, Tsukiji, tl--1--1, Cbuoku, Tokyo, Prof. I. Webster Medical Research Council South Africa, Nat Institute for Occupational Diseases, P.0. Johannesburg, South Africa.1 Physics and Chemistry Panel Dr * L. Le Bouffant 1. Laboratoire, du Centre D 'Etudes et Rcchorcb Charbonnages de France, Vcrneuill-cn-IIalJ a 60 - Creil, France. Mi'* G. V. Gibbs McGill University, Department of Epidemiol 3773' University Street, Montreal 110, Quel. Dr. S, Holmes Mr* A. Morgan Asbcstosis Research Council, c/o Turner Br Co. Ltd. P. 0: Box ^jO, Rochdale, England, I r> Atomic Energy Research Esiab)ishment, Heal Medical Division, Building "}GK, Harwell, 1 Prw'ilnnrl. !TIC Dr* F, D. Poolcy . Department of Mineral Exploitation, Universi of S* Vales and Monmouthshire, Newport Hoad, Vales, UK. Dr* S Spoil Dr. V. Timbrel1 Johns Manvillc Research and Engineering Ceni 159 Manvillc, New Jersey, USA. Medical Research Council, Pneumoconiosis Uni hospital, Pcnartli, Glamorgan, Vales, UK. Dr. R. du Toit Government Mining Engineer's Division, Depai Mines, P.. Box H 3 2 , Johannesburg, South Al Mr. V. H. Val ton Institute of Occupational Medicine, Roxburgh Place, Edinburgh EH 0 9SU, Scottane (Chairman) The panels met in a separate session and at the final session (Chai Gilson) prepared this report to the Director of .the International Agency 0J1 Cancer 1. The Committee was to report on the present evidence relating exposi asbestos dust to cancers, especially that obtained since the meeting of i Working Group on Asbestos Cancers in 1964. 2 t The Committee was to make recommendations for further research and priorities for work of immediate and long-term value. CO-ORDINATION OF INTERNATIONAL CO-OPERATION Following the meeting of the DICC Vorking Group on Asbestos and Cai 1964, a Sub-Committee of the UJ.CC Commission on Geographical Pathology ai Environmental Carcinogens (Chairman^Dr. J. Higginson) was formed to c o - oj work required to achieve the recommendations. the In April 1970 agreements between the UCC and/lARC led to the wind; up of the UICC Sub-Coimnittoe and the TAHC taking on responsibility for tl Committee's work and extending it by supporting certain projects on asbe. . cancers -in several countries. The Agency has done this as part of their programme of investigating environmental carcinogens. Common membership of policy, _ ' In October 1972 the IARC hold an-international Conference with 13? participant*? from 20 countries to review all the evidence relating nsbosi cancers. Subsequently the Advisory Committee prepared its report. This divided into two sections. First, a general review in the form of ansvei a number of important general questions about the relation of asbestos t( of different sites and, secondly, recommendations for further research. GENERAL REVIEW 1 * re all major commercial types of asbestos able to cause lung carci Yes. Since 19^t the evidence of a causal relationship has been inc by epidemiological studies shoving exposure-response relations for .the i of lung carcinomas. The production of lung carcinomas in certain animal types of asbestos supports this conclusion. The epidemiological evident however;, shows that there arc clear differences in -risk with type* of f i nature of exposure. 2 Is there evidence of an increased risk of lung carcinoma at low le1 exposure to asbestos, such as have been encountered by the general popu urban areas? The evidence of an exposure-response relationship based in part on measurements and in part on the type of job within the industry suggest excess lung carcinoma risk is not detectable when the occupational expc_ been low. These low occupational exposures have almost certainly been greater titan that to the public from general air pollution. 3*. Since 196u lias the evidence relating mesotheliomas changed? past exposure to asbestos r The evidence lias been greatly strengthened by further prospective retrospective mortality studies in' many countries of populations expos There is evidence that nil commercial types of asbestos except anthopl occupations and with the typo of asbestos has increased. The risk is nr with croc5.do3.itc, less with mnositc and apparently less with chrysotilo. amositc and chrysotilo there appears to bo a higher risk in manuf acturi n in mining and milling. Tlierc is also evidence from population studies t proportion of eases of mesothcl i.oma have* no known association with expos asbestos. 4. Is there-evidence of an increased risk-of mesothelial cancers at lo of exposure to asbestos, such as have been encountered by the general po in urban areas? . There is evidence of an association of mesothelial tumours with ail pollution in the neighbourhood of.croci del ite' mines and of factories usi mixtures of asbestos fibre types. The evidence relates to conditions r.u years ago. There is evidence of-no excess risk of mesotheliomas from re air pollution which has existed in the. neighbourhood of chrysotilo and i mines. There arc reported differences on incidence of mesothelioma bet*. urban and rural areas, the causes of which have not been established. % no evidence of a risk to the general public at present.21* 5. Since 1964 has the evidence changed on the importance of other fac such as. cigarette smoking, waxes, oils and trace elements as contribute to the cancer risks? The evidence has accumulated indicating: (1) Cigarette smoking is an important factor enhancing the lung c.r risk in asbestos-exposed workers, in both men and women. Asbc workers have .specially strong grounds for giving up smoking tc protect their health. No association has been demonstrated between cigarette .smoking and mesotheliomas. (2) Animal experiments designed thus far to test the importance. oJ wavoii and oils as contributory factors in the production of bo relevant* . iI (3) From animal experiments there arcfno good clues suggesting that trace elements are likely to be a major factor in the production of asbestos cancers. 6c 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 ri.sk of some other types of cancers (in ad to bronchial and mcsothol i.al), especially those of the gastro-intestinal t The excess of t)1cse tumours is relatively small compared with that for bro cancer. Evidence for an association with ovarian tumours has not been sup by the first large mortality survey of women previously exposed to asbesto 7 . Is there evidence of an increased risk of cancer resulting from asbot fibres j.n'csmit in water, beverages, food or in the fluids used for the administration 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 expo? asbestos such as have been encountered by the general population in urban There is at present no evidence of lung damage by asbestos to the ge; public* The amount of asbestos in the lungs of members of the general pul ir very small, compared to those occupationally exposed. It is great o:.d ' naoerios is mined or worked and lowest in rural areas. Has the relationship between asbestos exposure and the development o pleural plaques been established? Pleural plaques hove been associated with past exposure to all commo typos of asbestos. Put additional factors, other than asbestos itself, f involved. The plaques may remain fibrous or become calcified. Not all ] plaques are associated with asbestos. v/hich will require close co-operation between the Panels are marked / EPIDEMIOLOGY The Panel agreed that asbestos related cancers occur in several site in the body.. The incidence of the different cancers varies with a numbo definable factors and for other reasons, such as competing causes of doa' Epidemiological studies will usually provide information on more than on of cancer* Research directed at only a single type may, on occasions, b> useful but in general the inevitable uncertainties, in some cases in the differential diagnosis of, for example, peripheral lung carcinomas and ; mesotheliomas, and between peritoneal mesotheliomas and other intra-abdo.* cancers will require that more than one type is st,tidied at the same time The Panel recognised that some of the cpidciniological projects coni' only be pursued if there was close co-opera!ion between epidemiologists, pathologists, physicists and chemists, and others, because their success depend upon the development of improved techniques, some of which arc re: to in the recommendations of the other two Panels. PROJECTS (i) Further development of objective methods for early detection and su: of effects caused by asbestos. Topics foi* particular study include : (a) Immunological techniques for screening for fibrosis t. 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 U/C s> Classification (1971 ) radiographyt including the use of 100 mm films* ( n Development of statistical procedures for analysis and presentation of serial observations. (2 ) Evaluation of the usefulness of early detection in the prevention progressive fibrosis and asbestos cancers, also in the identification hazardous conditions. Routine health surveillance of industrial populr ---------- --- ---' should should be designed to assist epidemiological studies and/includo mcasui recording of environmental dust levels. Surveillance of new entrants c particularly valuable. Arrangements should be made to register workers theirnorbidity and mortality experience can be studied even after cessr exposure to asbestos. . (3 ) Assessment of excess cancer risks following exposure to only one 1 fibre. J Chrysotilc : The much higher cancer risk reported for chi textile workers compared with mine and mill workers requ: explanation. How much is explicable by differences in s past airborne fibres and/dustiness? There is need to make mo: of past dust records for relating to indices of disease. (b) Amosito: The excess lung carcinoma and mesothelioma ri apparently much greater in the manufacturing and applica sections of the industry than in the mining and milling type of fibre. What-arc the important factors in this r d ifferen c e? (c) Crocldel 11e : Further studies are required in occupatio] exposed only to crocidolite or amosi.te or chrysotilc in manufacturing and application parts of the industry to < c more clearly differences in risks due to different fibre mesotheliomas (if possible by coll type) in (a) national survey of / mesotheliomas, (b) representative samples of cases arising in groups vi a definable past exposure. (p) 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 general population. ' (0) Studies to relate amount and type of asbestos.in the lung and csti of past dust exposure and interval since last exposure, (9) Experimental and epidemiological studies- to investigate possible diffoyencos of effect of continuous low and intermittent high exposure asbestos. .. (10) Opj'jortunitics afforded by intcrcurrent deaths should be used to interrelate radiographic appearances, lung pathology, respiratory func* dust content, and type in asbestos workers. Standardised techniques ai classification recommended by the Pancd s should be used. ( u ) Investigate the prognostic significance and actiologic.nl factors the development of calcified and uncalcificd pleural plaques in differ environmentse (1 2 ) Investigate talc-exposed groups in mining and manufacturing to e any differcnccs .in morbidity or mortality which might be related to t): and shape-of the fine respirable particles. 0 3 ) Development of cost/benefit analyses to study the health, safety social and economic interrcl at ions of the use of asbestos. The Panel rev5.eved the progress made on the 196(1 UICC recommendation It was agreed that considerable progress had been made on the majority ox recommendations* Some require further study, or modification of previous methods of investigation; these are included in the list of rccommendatio that follows* The recommendations are divided into three categories, tnor anatomy and histology, clinical research, and experimental studies* PROJECTS Morbid Anatomy and Histology 1 * Asbesto.si s * t ' l ) Further consideration should be given to methods for deten the amounts, types and structural features of asbestos in tissue* A Sub Committee should be established with members of the Piiysi.es and Chomistr Pane},, and others to accelerate work on tins problem* (2 ) The methods for assessing the severity of asbestosis (see should be tested for consistency by different observers* 2 Carcinoma / (l) An investigation of whether reduction of asbestos exposure 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* 1 (1) fhc^International Panel cf Pathologists and National Panels established folloving the 196^ 2 meeting " have served a useful purpose. It recommended that panels be established in other countries and membership the International Panel be extended. The main purposes of these Panels i to ensure uniformity of diagnostic criteria and recording of histological types of diffuse mesotheliomas. Collaborative study of histology slides National Panels is recommended. The diagnosis of mesothelioma can be mac exfoliative cytology of the pleural fluid. If the cytological diagnosis made by a competent cytologist, biopsy may.be unnecessary. (2) To improve consistency of diagnosis there is an urgent need a Comprehensive Atlas on mesotheliomas or alternatively, for inclusion c enlarged section on mesotheliomas in the new edition of the \ft]0 Monograp) Tumours of the Lung. Criteria for diagnosis by exfoliative cytology and description of the fine structure of mesotheliomas should be included. C1 5.n :1c a .1 P o s c arc.h - / o.) Monitoring by immunological methods of populations exposed asbestos should be investigated to ascertain whether it is possible to recognize those who. arc developing, or will develop, tumours. :(a) The use of chromatographic methods for the study of tnivcopo and other tumour-associated substances in pleural fluids should be cxplo Sensitive methods might be developed and applied to identify secretory p of mesotheliomas in blood and urine. . The International Panel consists of: Dr. M. Kannerstoin (USA), Prof. D (Canada), Dr. L. Moorman (Finland), Prof. Y/.T.B. McCaugbcy (Dire) , Prof. 0'1'G), Dr. 11. T. PI ant eye t (N'othorl ands ), Dr. E, Poitzsoh, (GPU), Pro f. (Italy) 5 Prof. I. Y/obster (South Africa), and Dr. J.C.Vagner (tin) as Sec Great Britain, South Africa, United States, 'Canada, Netherlands. * (l) Information is required about the role of fine particles, e influence .of fibre size, in the' induction of tumours." Those studies she extended to include fibres other than asbestos. A Sub-Committee should established to review the need for, and arrange the distribution of stai samples of asbestos and other fibres in addition to the Ul'CC Reference f / (2) The fate of inhaled particles of various sizes, shapes and compositions, should be studied to determine, more precisely the quantit sites of initial deposition, change within the body and later retention feasibility of increasing fibre elimination by various methods should b explored. Studies should be made of means of reducing the'fibrogcnicit carcinogenicity of fibres already retained in the lungs. (3) The use of `cell and organ culture, including mosothelini i from nan and other species, should be further investigated with a view |. . . developing methods of screening dusts for fibrogenic and carcinogenic j ( h ) Further studies should be carried out to determine the na the combined effect on tumour induction when animals arc exposed to as dust and cigarette smoke, metals or other chemical carcinogens, i.nclud those which act systcmically such as nitrosamines. (3 ) Inhalation experiments should be extended to test various of fibre; of special interest are forms of chrysotilc and crocidolitc the finer grade materials. (6) It was felt that studies; of the pathological effects of on species other than rodents would be of value. (7) The effect of long-term ingestion of fibres of various s shapes and chemical compositions* should be studied. . (8) The effects of fibres and associated metals on the metal; of target organs should be investigated, The Panel reviewed the progress made on tre iyuu un. proposal.s for the preparation and characterization of the UICC reference of asbestos had been satisfactorily implemented, and the Panel rocommendc a list of references to papers featuring the samples should be distribute investigators in-this field. Considerable progress bad been made on met] identifying the type'of fibre in tissues but a quantitative method when : types of fibres were present had yet to be developed. The Panel discussed the further -contribution that physical and chem studios can make to research on the biological effects of asbestos; and o fibrous materials. Of especial interest are Die effects of fibre size a shape on the retention of material in the lungs, Due site of deposition, migration of fibres within the body, and their carcinogenic or other bic activity. The following recommendations were made: PROJECTS 1. Materials for experimental work a) Supplies of asbestos from relevant sources should be obtained w there is evidence of variation in geological form, trace element center significant biological findings. b) Small samples of various fibrous materials should be prepared : studies on the influence of fibre size and shape on carcinogenicity, purpose the samples, should be milled to different degrees of fineness. c) For' investigations on the influence of particle shape and size inhalation and subsequent fate of asbestos fibres a chrysotile and an of fibre length greater than the UJCC samples should be prepared. 2 . Methods a) There is an urgent need for the quantitative assessment, size and eharacteriz at ion of partir;] es and fibres in the lungs and other o 1 ''ir-Miods should be circuloted, international comr narrow ranges of diameter and length in sufficient quantities for inocuia experiments. Techniques for these purposes are urgently required, espcci in'view of the advantages such graded samples could provide for investiga the influence of these physical, factors on the carcinogenicity of fibres different materials* c) Since the degree of dispersion of fibres (especially chrysotile) in inoculation studies may have" a marked influence on their carcinogenic:.! methods are required for quantifying dispersion. d) Inhalation studios require precise control of the characteristics dust clouds. Improved methods of dispensing fibrous dusts in such invest need to be developed. e) Methods arc available for collecting the important size fraction; dust clouds in inhalation studies when the particles arc of compact shnpi Similar methods must be developed for fibrous particles. f) The present membrane filter methods of measuring the; levels of a asbestos dust require standardization This should be done by inter-lab trials on a continuing basis. Particle counting by electron microscopy also be developed. Gravimetric assessment methods and the automation of cotint inn 'should be explored. 3. Inhale.tion studles Considerable information is now.available on the deposition, retent migration of particles of compact shape. Recently developed methods, cs \. radio-active tracer techniques, should be used to obtain similar knovlec fibrous particles. This' information is needed to identify the biologic; important size fraction and to help interpretation of epidemiological at pathological studios. x t v . n j ..< The use of both fibre counts and gravimetric methods for assessing a: dust concentrations should be encouraged. Data collected over an cxtcndc- will be particularly valuable in identifying the parameters of the dust w be correlated with epi.dcmiol ogical evidence on the health hazard. Phy.slcs and Chomi.stry Panel It is recommended that an international Panel be cstablished to assi implementing these recommandtions. The Panel would periodically review requirements for materials for experimental work; provide guidance on phy and chemical problems; and arrange national and international standardize' trials.