Document XygL4aZKr1zvemzmmXyvBgJ

FILE NAME: Asten Hill (AH) DATE: 1972 Oct DOC#: AH043 DOCUMENT DESCRIPTION: Published Report from IARC and W HO "The Biological Effects of Asbestos" Lyon, France--October 5-6, 1972 REPORT OF TH E A D V IS O R Y CO M M ITTEE ON ASBESTOS CANCERS TO THE DIREC TO R OF THE IN T E R N A T IO N A L AGENCY FOR RESEARCH ON CANCER. A D IVISIO N OF THE W ORLD HEALTH O R G AN IZATIO N . The In te rn a tio n a l Agency fo r Research on Cancer has been concerned fo r several years w ith the problem o f asbestos as a cancer-producing agent. The th ird o f a series o f meetings concluded recently at IA R C headquarters, Lyo n . France, after assessing advances made in th a t fie ld and proposing new topics o f research. There were 130 pa rticip a n ts fro m 20 countries a t the meeting, which was organ ized jo in tly w ith the Pneum oconiosis Research U n it o f the Medical Research Council o f Great B rita in . The Advisory Com m ittee consisted o f three panels-- epidem iology, pathology, physics and chem istry. The Proceedings o f the meeting w ill be published by the W orld Health O rganization in Geneva at a later date. TERMS OF REFERENCE 1. The C o m m itte e was to re p o rt on the present evidence relating exposure to asbestos d u st to cancers, especially th a t o b tained since the m eeting o f the UICC W o rkin g G rou p on Asbestos Cancers in 1964. 2. The C o m m itte e was to make recom m endations fo r fu rth e r research and in d i cate p rio ritie s fo r w o rk o f im m ediate and long-term value. CO -O RDINATION OF IN T E R N A T IO N A L CO-OPERATION \ F o llo w in g the m eeting o f the UICC W orking G roup on Asbestos and Cancers in 1964, a Sub-Com m ittee o f the UICC Commission on Geographical Pathology and E n viro n m e n ta l Carcinogens (Chairm an, D r. J. Higginson) was form ed to co -ordinate w o rk required to achieve the recom m endations. In A p ril 1970 agreements between the UICC and the IA R C led to the w inding up o f the UICC Sub-Committee and the IARC taking on responsibility fo r the Sub-Com m ittee's w o rk and extending it by supporting certain projects on asbestos cancers in several countries. The Agency has done this as p a rt o f their w ider programme o f investigating environm ental carcinogens. Com mon memberships between the UICC Sub-Com m ittee and the Com m ittee advising the IA R C ensured c o n tin u ity of policy. In O cto b er 1972 the IA R C held an in te rn a tio n a l Conference w ith 137 par tic ip a n ts fro m 20 co u n trie s to review all the evidence relating asbestos w ith cancers. Subsequently the A d viso ry C o m m itte e prepared its rep o rt. This is d i vided in to tw o sections. F irst, a general review in the fo rm o f answers to a n um ber o f im p o rta n t general questions a b o u t the relation o f asbestos to cancers o f d iffe re n t sites and. secondly, recom m endations fo r fu rth e r research. G ENERAL REVIEW 1. A re all m a jo r com m ercial types o f asbestos able to cause lung carcinoma? Yes. Since 1964 the evidence o f a causal relationship has been increased by epidem iological studies showing exposure-response relations for the incidence o f lung carcinom as. The p ro d u c tio n o f lung carcinom as in certain animals by all types o f asbestos supports this conclusion. The epidem iological evidence in man, how ever, shows th a t there are clear differences in risk w ith type o f fib re and nature o f exposure. CONFIDENTIAL- In Re: Bickham. et al. v. Met Life. etaL ^C/LA 007744 2. Is there evidence o f an increased risk o f lung carcinom a at lo w levels of exposure to asbestos, such as have been encountered by the general pop ulatio n in urban areas? The evidence o f an exposure-response re la tio n sh ip based in p a rt on past dust measurements and in part on the type o f jo b w ith in th in d u s try suggests th a t an excess lung carcinom a risk is n o t detectable when the occupational exposure has ben low . These lo w occupational exposures have alm ost certainly been much greater than that to the public from general air p o llu tio n . 3. Since 1964 has the evidence relating past exposure to asbestos and m esotheli omas changed? The evidence has been greatly strengthened by fu rth e r prospective and re t rospective m o rta lity studies in m any co u n trie s o f pop ulatio n s exposed to asbes tos. There is evidence th a t all com m ercial types o f asbestos except a n th o p h y llite m ay be responsible. Evidence fo r an im p o rta n t difference in risk in d iffe re n t occupations and w ith the type o f asbestos has increased. The risk is greatest w ith c ro c id o lite , less w ith amosite and apparently less w ith ch ryso tile . W ith amosite and ch ryso tile there appears to be a higher risk in m an u fa ctu rin g than in m ining and m illin g . There is also evidence fro m p o p u la tio n studies th a t a p ro p o rtio n o f cases o f m esotheliom a have no kn o w n association w ith exposure to asbestos. f 4. Is there evidence o f an increased risk o f m sothlial cancers at lo w levels o f exposure to asbestos, such as have been encountered by the general p o p ulatio n in urban areas? There is evidence o f an association o f m sothlial tum ours w ith air p o llu tio n in the neighbourhood o f c ro c id o lite mines and o f factories using m ixtu re s of asbestos fib re types. The evidence relates to c o n d itio n s m any years ago. There is evidence o f no excess risk o f m esotheliom as fro m asbestos air p o llu tio n which has existed in the neighbourhood o f ch ryso tile and amosite mines. There are reported differences on incidence o f m esotheliom a between urban and rural areas, the causes o f w hich have n o t been established. There is no evidence o f a risk to the general p u b lic at present. 5. Since 1964 has the evidence changed on the im p orta n ce o f other factors such as cigarette sm oking, waxes, oils and trace elements as c o n trib u to ry factors to the cancer risks? The evidence has accum ulated in d ica tin g : (a) Cigarette sm oking is an im p o rta n t fa c to r enhancing the lung carcinom a risk in asbestos-exposed workers, in both men and wom en. Asbestos workers have specially strong grounds fo r giving up smoking to protect th e ir health. N o association has been dem onstrated between cigarette smoking and mesotheliomas. (b) Anim al experim ents designed thus fa r to test the im portance o f waxes and oils as c o n trib u to ry factors in the p ro d u c tio n o f m esotheliom a have shown these contam inants are u n lik e ly to be relevant. (c) From anim al experim ents there are no good clues suggesting th a t trace elements are lik e ly to be a m ajor fa c to r in the p ro d u ctio n o f asbestos cancers. 6. W hat o th er types o f cancer are related to exposure to asbestos? Prospective surveys o f occupational groups exposed to asbestos have in general shown a small excess risk o f some o th e r types o f cancers (in a d d itio n to bronchial and m sothlial), especially those o f the gastro-intestinal tract. The excess o f these tu m o rs is relative ly small com pared w ith th a t fo r bronchial cancer. Evidence fo r an association w ith ovarian tu m o u rs has n o t been supported by the firs t large m o rta lity survey o f w om an pre vio u sly exposed to asbestos. 7. Is there evidence o f an increased risk o f cancer resulting fro m asbestos fibres present in w ater, beverages, fo o d or in the flu id s used fo r the a d m in is tra tio n of drugs? 2 CONHDENTIAL-' In Re: Bickham. et al. v. Met Life, ei al. AC/LA 007745 RECOM M ENDATIONS FOR FURTHER RESEARCH EPIDEM IOLOGY PROJECTS Such evidence as there is does n o t in dicate any risk. 8. Is there evidence o f a risk o f lung fibrosis fro m lo w levels o f exposure to asbestos such as have been encountered by the general p o p u la tio n in urban areas? There is at present no evidence o f lung damage by asbestos to the general p u b lic. The a m o u n t o f asbestos in the lungs o f members o f the general p u b lic is very small, com pared to those o ccu p a tio n a lly exposed. It is greatest where asbestos is m ined or w o rked and low est in rural areas. 9. Has the relatio n sh ip between asbestos exposure and the developm ent of pleural plaques been established? Pleural plaques have been associated w ith past exposure to all com m ercial types o f asbestos. B u t a d d itio na l factors, o ther than asbestos itself, are involved. The plaques may rem ain fib ro u s or become calcified. N o t all pleural plaques are associated w ith asbestos. Projects w h ich the Panels rated high in p rio r ity are marked *; those w hich w ill require close co-operation between the Panels are m arked 4- . The Panel agreed th a t asbestos related cancers occur in several sites in the body. The incidence o f the d iffe re n t cancers varies w ith a number o f definable factors and fo r o th e r reasons, such as co m p e tin g causes o f death. E pidem iological studies w ill usually provide in fo rm a tio n on more than one type o f cancer. Research d irecte d at o n ly a single type m ay, on occassions, be useful b u t in general the in e vita b le uncertainties, in some cases in the d iffe re n tia l diagnosis o f. fo r example, peripheral lung carcinomas and pleural mesotheliomas, and between peritoneal mesotheliomas and other intra-abdom inal cancers w ill require th a t m ore than one type is studied at the same tim e. The Panel recognised th a t some o f the epidem iological projects could on ly be pursued if there was close co-operation between epidem iologists, pathologists, physicists and chemists, and others, because th e ir success w ill depend upon the developm ent o f im proved techniques, some o f w hich are referred to in the recom m endations o f the o th er tw o Panels. 1. F u rth e r developm ent o f objective m ethods fo r early d e tectio n and surveillance o f effects caused by asbestos. Topics fo r p a rticu la r study include: (a) Im m u n o lo g ica l techniques fo r screening fo r fibrosis and neoplasia. (b) F un ctio n a l tests o f changes in the peripheral airways. (c) D e te ctio n o f pleural th icke n in g. (d) Assessment o f the s p e c ific ity o f small irregular opacities in the chest radiograph as d efined in the ILO U /C C lassification (1971). (e) Tests o f the usefulness o f d iffe re n t techniques o f chest radiography, in clu d in g the use o f 100 m m film s. (f) D evelopm ent o f statistical procedures fo r analysis and presentation of serial observations. -A 2. E valuation o f the usefulness o f early de tectio n in the prevention of progressive fib ro sis and asbestos cancers, also in the id e n tific a tio n o f hazardous c o n d itio n s. R o u tin e health surveillance o f in d u stria l populations should be designed to assist e p idem iological studies and should include measurement and recording o f e n viro n m e n ta l dust levels. Surveillance o f new entrants could be p a rtic u la rly valuable. Arrangem ents should be made to register w orkers so that th e ir m o rb id ity and m o rta lity experience can be studied even after cessation of exposure to asbestos. 3. Assessment o f excess cancer risks fo llo w in g exposure to only one type of fibre. (a) C h ryso tile : The m uch higher cancer risk reported fo r ch ryso tile te x tile 3 CONFEDENTLAL- In Re: B ickham . et al. v . M et L ife, et al. &.C/LA 0 0 7 " workers compared w ith mine and m ill workers requires explanation H o w m uch is explicable by differences in size o f airborne fibres and past dustiness? There is need to make more use o f past dust records for relating to indices o f disease. (b) A m o site : The excess lung carcinom a and m esotheliom a risk is ap p are n tly m uch greater in the m a n u fa ctu rin g and a p p lic a tio n sections o f the in d u stry than in the m ining and m illing o f this type o f fibre. W hat are the im p o rta n t factors in this reported difference? (c) C ro c id o lite : F u rth e r studies are required in occu p atio n a l groups exposed o n ly to c ro c id o lite or amosite o r ch ry s o tile in the m anufacturing and application parts o f the in dustry to establish more clearly differences in risks due to d iffe re n t fibres. ' 4-4. Studies o f the a m o u n t and type o f asbestos in the lungs o f cases o f m esotheliom as (if possible by cell type) in (a) national survey o f m esotheliom as, (b) representative samples o f cases arising in groups w ith a definable past exposure. 5. Studies o f secular changes in incidence o f pleural and peritoneal mesotheliomas nationally and internationally. 6. Epidem iological studies to investigate the association between past exposure * to asbestos and cancer o f sites o th e r than lung, pleura, and p eritoneum . 7. Studies o f secular trends in the asbestos c o n te n t o f the lungs in the general population. ` -A8. Studies to relate a m o u n t and type o f asbestos in the lung and estimates o f past dust exposure and interval since last exposure. 9. E xperim ental and epidem iological studies to investigate possible differences o f e ffe c t o f co n tin u o u s lo w and in te rm itte n t high exposure to asbestos. 10. O p p o rtu n itie s a ffo rd e d by in te rc u rre n t deaths should be used to in terrelate radiographic appearances, lung pathology, respiratory fu n ctio n , dust content, and typ e in asbestos workers. Standardised techniques and classification recom m ended bv the Panels should be used. 11. Investigate the prognostic significance and aetiological factors in the developm ent o f calcified and uncalcified pleural plaques in d iffe re n t e n viro n m e n ts. 12. Investigate talc-exposed groups in m in in g and m an u fa ctu rin g to establish any differences in m o rb id ity or m o rta lity w h ich m ig h t be related to the a m o u n t and shape o f the fin e respirable particles. 13. D evelopm ent o f c o s t/b e n e fit analyses to study the health, safety, social and econom ic in te rre la tio n s o f the use o f asbestos. PATHOLOGY AN D EXPERIM ENTAL PATHOLOGY The Panel reviewed the progress made on the 1964 UICC recom m endations. It was agreed th a t considerable progress had been made on the m a jo rity o f the recommendations. Some require fu rth e r study, or m od ifica tio n o f previous m ethods o f in ve stig a tion ; these are included in the lis t o f recom m endations th a t follow s. The recom m endations are divided in to three categories, m o rb id anatomy and histology, clinical research, and experim ental studies. PROJECTS M ORBID A N A TO M Y AN D HISTOLOGY 1. Asbestosis * (a) F u rth e r consideration should be given to m ethods fo r d e te rm in in g the amounts, types and stru ctu ra l features o f asbestos in tissue. A S ub-C om m ittee should be established w ith members o f the Physics and C hem istry Panel, and others to accelerate w o rk on this problem . (b) The m ethods fo r assessing the severity o f asbestosis (see paper 9) should be tested fo r consistency by d iffe re n t observers. et al v AC/LA 007747 2. Carcinoma ' (a) A n investigation o f w h e th er re d u ctio n o f asbestos exposure to levels b e lo w those p ro d u cin g asbestosis also abolishes excess risk o f carcinom a was considered im p orta n t. (b) A com parison o f lung carcinomas in persons occupationally exposed to asbestos and those n o t so exposed, in clu d in g bo th cigarette sm okers and non-sm okers, in respect o f sites o f o rig in and c yto lo g y o f tu m o u rs and presence o r absence o f asbestosis, w o u ld be o f value. 3. Mesotheliomas (a) The In te rn a tio n a l Panel o f P athologists1 and N ational Panels established fo llo w in g the 1964 m ee tin g 2 have served a useful purpose. It is recom m ended th a t panels be established in o th er countries and m em bership o f the In te rn a tio n a l Panel be extended. The m ain purposes o f these Panels is to ensure u n ifo rm ity o f diagnostic criteria and recording of histological types of diffuse m esotheliom as. C o lla b o ra tive stu d y o f histo lo g y slides in N ational Panels is recom m ended. The diagnosis o f m esotheliom a can be made by e x fo lia tiv e c y to lo g y o f the pleural flu id . I f the c yto lo g ica l diagnosis is made by a c o m p e te n t cy to lo g is t, biopsy m ay be unnecessary. (b) T o im prove consistency o.f diagnosis there is an urgent need fo r a Com prehensive A tla s on m esotheliom as, o r a lternatively, fo r in clusion o f an enlarged section on mesotheliom as in the new edition o f the WHO M onograph on Tum ours o f the Lung. C riteria fo r diagnosis by exfoliative cyto lo g y and a d e scrip tio n o f the fine stru ctu re o f m esotheliom as should be included. C linical Research (a) M o n ito rin g by im m u n o lo g ica l m ethods o f pop ulatio n s exposed to asbestos should be investigated to ascertain w h e th er it is possible to recognize those w h o are developing, o r w ill develop, tum ours. (b) The use o f ch ro m a to gra p h ic m ethods fo r the study o f m ucopolysaccharide and other tumour-associated substances in pleural fluids should be e xp lo re d . Sensitive m ethods m ig h t be developed and applied to id e n tify secretory products o f mesotheliomas in blood and urine. F urther Experim ental Studies (1) In fo rm a tio n is required about the role o f fine particles, especially in fluence o f fib re size, in the in d u c tio n o f tum ours. These studies should be extended to in clu d e fibres o th e r than asbestos. A Sub-C om m ittee should be established to review the need fo r, and arrange the d istrib u tio n o f standard samples o f asbestos and o th e r fibres in a d d itio n to the UICC Reference Samples. 4- (2) The fate o f inhaled particles o f various sizes, shapes and chem ical co m p o sitio n s, should be studied to determ ine more precisely the qua ntitie s and sites o f in itia l d e p o sitio n , change w ith in the body and later re te n tio n . The fe a s ib ility o f increasing fib re e lim in a tio n by various m ethods should be exp lo re d . Studies should be made o f means o f reducing the fib ro g e n ic ity and ca rcino g e n icity o f fibres already retained in the lungs. (3) The use o f cell and organ cu ltu re , in clu d in g m sothlial tissue fro m man and o th e r species, should be fu rth e r investigated w ith a view to developing m ethods o f screening dusts fo r fibrogenic and carcinogenic properties. The International Panel consists of: Dr. M. Kannerstein lUSA), Prof. . Magner (Canada). Dr. L. Meurman (Finland), Prof. W.T.E. McCaughey (Eire), Prof. H. Otto (FRG), Or. H.T. Planteydt (Netherlands), Dr. E. Roitzsch, (GDR), Prof. L. Santi (Italy). Prof. I. Webster (South Africa), and Dr. J.C. Wagner (UK) as Secretary. 2 Great Britain. South Africa. United States. Canada. Netherlands. AC/LA 007748 (4) F u rth e r studies should be carried o u t 10 determ ine the nature o f the com bined e ffe ct on tu m o u r in d u c tio n w hen animals are exposed to asbestos dust and cigarette sm oke, metals o r o th e r chem ical carcinogens, including those w hich act system ically such as nitrosam ines. (5) In h alatio n experim ents should be extended to test various types of fib re ; o f special interest are form s o f ch ry s o tile and cro cid o lite including the fin e r grade m aterials. (6) I t was fe lt th a t studies o f the p athological effects o f asbestos on species o th er than rodents w o u ld be o f value. (7) The e ffe c t o f long-term ingestion o f fibres o f various sizes, shapes and chemical co m p o sitio n s should be studied. (8) The effects o f fibres and associated metals on the m etabolism o f target organs should be investigated. PHYSICS AN D C H E M ISTR Y The Panel reviewed the progress made on the 1964 UICC Recomm endations. The proposals fo r the preparation and characterization of the UICC reference samples o f asbestos had been s a tis fa c to rily im plem ented, and the Panel recom m ended th a t a list o f references to papers featuring the samples should be d istrib u te d to investigators in this fi_eld. Considerable progress had been made on m ethods o f id e n tify in g the typ e o f fib re in tissues b u t a q u a ntita tive m ethod when several types o f fibres were present had y e t to be developed. The Panel discussed the fu rth e r c o n trib u tio n th a t physical and chemical studies can make to research on the b io lo g ica l effects o f asbestos and other fib ro u s m aterials. O f special in te re st are the effects o f fib re size and shape on the re te n tio n o f m aterial in the lungs, the site o f d e position, the m ig ra tio n o f fibres w ith in the body, and their carcinogenic or other biological activity. The fo llo w in g recom m endations were made: PROJECTS '/I. Materials fo r experim ental w o rk (a) Supplies o f asbestos fro m relevant sources should be obtained where there is evidence o f va riatio n in geological fo rm , trace elem ent co n ten t or significant biological findings. (b) Sm all samples o f various fib ro u s m aterials should be prepared fo r studies on the in flu e n ce o f fib re size and shape on carcinogenicity. For this purpose the samples should be m ille d to d iffe re n t degrees o f fineness. (c) F or investigations on the in flu e n ce o f p article shape and size, on the in h a la tio n and subsequent fate o f asbestos fibres a ch ryso tile and an am phibole o f fib re length greater than the UICC samples should be prepared. *2. M ethods (a) There is an u rgent need fo r the q u a n tita tive assessment, size analysis and characterization o f particles and fibres in the lungs and other organs. Details of available m ethods should be circu la te d , in te rn a tio n a l comparisons undertaken, m ethods standardized and new techniques developed. (b) No m ethods are at present available fo r the preparation o f fibres in narrow ranges o f diam eter and length in s u ffic ie n t quantities fo r in o cu la tio n experim ents. Techniques fo r these purposes are u rg e n tly required, especially in view o f the advantages such graded samples co u ld provide fo r investigating the influence o f these physical factors on the ca rcino g e n icity o f fibres o f d iffe re n t m aterials. (c) Since the degree o f dispersion o f fibres (especially chrysotile) used in in oculation studies may have a m arked influence on their carcinogenicity, m ethods are required fo r q u a n tify in g dispersion. (d) Inhalation studies require precise c o n tro l of the characteristics of the dust clouds. Im proved m ethods o f dispensing fib ro u s dusts in such investigations need to be developed. 6 CONFIDENTIAL- In Re: Bickham. et al y Met Life, ar al ' AC/LA 007749 (e) M ethods are available fo r collecting the im p o rta n t size fractions o f dust clouds in in h a la tio n studies when the particles are o f com pact shape. S im ila r m ethods m ust be developed for fibrous particles. (f) The present m em brane filte r m ethods o f measuring the levels o f a irbo rn e asbestos d u st require standardization. This should be done by in te r-la b o ra to ry trials on a co n tin u in g basis. Particle counting by electron m icro sco p y should also be developed. G ravim e tric assessment m ethods and the a u to m a tio n o f p a rticle co u n ting should be explored. 4- 3. In h a la tio n studies C onsiderable in fo rm a tio n is now available on the deposition, re te n tio n and m igration o f particles o f com pact shape. Recently developed methods, especially radio-active tracer techniques, should be used to o btain sim ilar knowledge fo r fib ro u s particles. T his in fo rm a tio n is needed to id e n tify the b io lo g ica lly im p o rta n t size fra c tio n and to help in te rp re ta tio n o f epidem iological and pathological studies. 4. O ccupational and environm ental studies T he use o f b o th fib re counts and g ra vim e tric m ethods fo r assessing asbestos d u st co n ce n tra tio n s should be encouraged. Data collected over an extended period w ill be p a rticu la rly valuable in id e n tify in g the parameters of the dust w h ich can be co rre la te d w ith epidem iological evidence on the health hazard. * 5. Physics and C h e m istry Panel I t is recom m ended th a t an in te rn a tio n a l Panel be established to assist in im p le m e n tin g these recom m endations. The Panel w o u ld p e rio d ic a lly review requirem ents fo r m aterials fo r experim ental w o rk; provide guidance on physical and chem ical pro b le m s; and arrange national and in te rn a tio n a l standardization trials. CONFIDENTIAL- In Re: Bickham. et al. v,_ Met Life, et aL 7 AC/LA 007750 E p id e m io lo gy Panel Or. M. Becklake M cG ill U niversity, Departm ent of Epidem iology & Health, 3775 University Street. M ontreal 110, Quebec, Canada. Dr. H. Bohlig Chefarzt der S trahlenabteilung des Stdtischen, Krenkenhausses Ldenscheid, 588 Ldenscheid, Germany, Dr. N. Day U n it o f E p id e m io lo gy and Biostatistics, In te rn a tio n a l Agency fo r Research on Cancer, 150 Cours A lb e rt Thomas, 69008, Lyon, France. P rof. P. C. Elmes D epartm ent o f Therapeutics and Pharmacology, Queen's U niversity o f Belfast; In s titu te o f C linical Science. Grosvenor Road, 8elfast, BT12 6BJ, N. Ireland, UK. Dr. J. C. Gilson Medical Research C ouncil, Pneum oconiosis U n it, Llandough H o spital, Penarth. Glam organ, Wales, U K . (Chairm an) Dr. J. Lepoutre Medical Departm ent, N .V . E ternit, Kapelle-op-den-Bos, Belgium. Prof. J. C. M cDonald M cG ill U niversity, Departm ent of Epidem iology & Health, 3775 U niversity Street. M ontreal 110, Quebec, Canada. M r. C. E. Rossiter Medical Research C ouncil, Pneum oconiosis U n it, Llandough H ospital, Penarth, G lam organ, Wales, U K . $ D. H. Sakabe Departm ent o f Industrial Physiology, M inistry of Labour National Institute of Industrial Health, 2051 K izukisum ioyoshi-C ho, Kawasaki, Japan. * D r. 1. J. S e lik o ff Departm ent o f M edicine, M ount Sinai School o f M edicine, F ifth Avenue and 100th Street, New Y o rk, N .Y. 10029, USA. Dr. G. K. Sluis-Cremer South A fric a n Medical Research C o u n cil, N ational Research In s titu te fo r O ccupational Diseases, P .0 . Box 4 7 8 8, Johannesburg, S. A fric a . Dr. W. Sm ither Cape Asbestos Co. Ltd. 114 Park Street, London W IY 4AB England, U K . Dr. G. W right Division o f M edicine, St. Luke's Hospital, 11311 Shaker Boulevard, Cleveland, O hio 44101, USA. Pathology Panel Dr. A . C. A lliso n M r. G. Berry D r. P. Bogovski Dr. M. Kannerstein Prof. W .T.E. McCaughey Prof. D. Magner Prof. H. Otto Dr. H. T. Planteydt Dr. M. Stanton D r. J. C. Wagner C linical Research Centre, W atford Road, H arrow , Middlesex, HA1 3UJ, UK. Medical Research C o u n cil, Pneum oconiosis U n it, Llandough H ospital, Penarth, G lam organ, Wales, U K . U n it o f E n viro n m e n ta l Carcinogens, In te rn a tio n a l Agency fo r Research on Cancer, 150 Cours A lb e rt Thomas, 69008, Lyon, France. Pathology Departm ent, Barnert Memorial Hospital Centre, 680 Broadway, Paterson, N.J. 07514, USA. School o f Pathology, T rin ity College, University o f D u b lin . D u blin 2, Eire. Canadian T um o u r Reference Centre, D epartm ent o f Pathology, U niversity of O ttaw a. O ttaw a, O ntario, K IN 6N5, Canada. D ire c k to r des Pathologischen In s titu ts der Beurhausstrase 40. 46 D o rtm und, W. Germany. Stadt Krankenanstalten Stichting Streeklaboratorium N e th e rla n d s . "Z e e la n d ". N oorpoortplein M iddelburg. Departm ent o f Health, Education and Welfare, National Institu te o f Health. Bethesda, MD 20014, USA. Medical Research C o u n cil, Pneum oconiosis U n it, Llandough H ospital, Penarth. G lam organ. Wales. U K . (Chairm an) CONFIDENTIAL- In Re: Bickham, et aLjL . Met Life, et al. 3 aC/LA 007751 $ \ __> o 4 E p id e m io lo gy Panel Or. M. Becklake Dr. H. Bohlig Dr. N. Day P rof. P. C. Elmes D r. J. C. Gilson Dr. J. Lepoutre Prof. J. C. M cDonald M r. C. E. Rossiter D. H. Sakabe * D r. 1. J. S e lik o ff Dr. G. K. Sluis-Cremer Dr. W. Sm ither Dr. G. W right P athology Panel Dr. A . C. A llison Mr. G. Berry D r. P. Bogovski Dr. M. Kannerstein Prof. W .T.E. McCaughey Prof. D. Magner ' Prof. H. Otto Dr. H. T . Planteydt Dr. M. Stanton Dr. J. C. Wagner McGill U niversity, Departm ent of Epidem iology & Health, 3775 University Street. M ontreal 110, Quebec, Canada. C hefarzt der S trahlenabteilung des Stdtischen, Krenkenhausses Ldenscheid, 588 Ldenscheid, Germany. U n it o f E pidem iology and Biostatistics, In ternational Agency fo r Research on Cancer, 150 Cours A lb e rt Thomas, 69008, Lyon, France. Departm ent o f Therapeutics and Pharmacology, Queen's U niversity o f Belfast; In stitu te o f Clinical Science, Grosvenor Road, Belfast, BT12 6BJ, N. Ireland, UK. Medical Research C ouncil, Pneumoconiosis U n it, Llandough H ospital, Penarth. G lam organ, Wales, U K . (Chairm an) Medical D epartm ent, N .V . E ternit. Kapelle-op-den-Bos, Belgium . M cG ill U niversity, Departm ent of Epidem iology & Health, 3775 University Street. M ontreal 110, Quebec, Canada. Medical Research C o u n cil, Pneumoconiosis U n it, Llandough H o sp ita l, Penarth, G lam organ, Wales, U K . Departm ent o f Industrial Physiology, M inistry o f Labour National In stitute of Industrial Health, 2051 Kizukisum ioyoshi-Cho, Kawasaki, Japan. D epartm ent o f M edicine, M ount Sinai School o f M edicine, F ifth Avenue and 100th Street, New Y o rk, N .Y . 10029, USA. South A fric a n M edical Research Council, N a tio n a l Research In s titu te fo r O ccupational Diseases, P.O. Box 4 7 8 8, Johannesburg, S. A fric a . Cape Asbestos Co. L td . 114 Park Street, L o ndon W IY 4 A B England, U K . Division o f M edicine, St. Luke's Hospital, 11311 Shaker Boulevard, Cleveland, Ohio 44101, USA. C linical Research C entre, W a tfo rd Road, H a rro w , M iddlesex, HA1 3U J, U K. Medical Research C ouncil, Pneumoconiosis U n it. Llandough H ospital, Penarth, Glam organ, Wales, U K . U n it o f E n viro n m e n ta l Carcinogens, In te rn a tio n a l Agency fo r Research on Cancer, 150 Cours A lb e rt Thomas, 69008, Lyon, France. Pathology D epartm ent, Barnen Memorial Hospital Centre, 680 Broadway, Paterson, N.J. 07514, USA. School o f Pathology, T rin ity College, U niversity o f D u b lin , D u blin 2, Eire. Canadian T um o u r Reference Centre, Departm ent o f Pathology, U niversity o f O ttaw a, O ttaw a, O n ta rio , K IN 6N 5, Canada. D ire c k to r des Pathologischen In stitu ts der Beurhausstrase 40, 4 6 D o rtm u n d , W. Germany. Stadt K ra n k e n a n s ta lte n Stichting Streeklaboratorium N e th e rla n d s . "Z e e la n d ", N oorpoortplein M iddelburg, Departm ent o f Health, Education and Welfare, N ational Institu te o f Health. Bethesda, MD 20014, USA. Medical Research C o u n cil, Pneum oconiosis U n it, Llandough H o sp ita l, Penarth, G lam organ. Wales, U K . (Chairm an) rn^rmpm-TAT - Tn Met Life, et al. Bickhain. et al. v. 3 AC/LA 007751 Prof. S. Watanabe Prof. I. Webster D epa rtm e n t o f P athology, N a tio n a l Cancer Centre. Research In s titu te . T s u k iji, 5-1-1, Chuoku, T o k y o , Japan. M edical Research C ouncil S outh A fric a , N ational Research In s titu te fo r O ccupational Diseases. P .0 . B o x 4 7 8 8, Johannesburg, South A fric a . Physics and C h e m istry Panel Dr. L. Le B ouffant L a b ora to ire du Centre D 'E tu d e s at Recherches des Charbonnages de France, V e rn e u ill-e n -H a lla tte , BP No. 27 60 -- C reil, France. M r. G. W. Gibbs M cG ill University, Departm ent o f Epidem iology & Health, 3775 University Street, M ontreal 110, Quebec, Canada. D r. S. Holmes Asbestosis Research C o u n cil, c/o T u rn e r Bros. Asbestos Co. L td . P.O. Box 40, Rochdale, England, UK. M r. A. Morgan A to m ic Energy Research E stablishm ent, Health Physics and M edical D ivision, B uilding 364, H arw ell, Berks., England, UK. Dr. F. D. Pooley D e p a rtm e n t o f M ineral E x p lo ita tio n , U nive rsity College o f S. Wales and M on m o u thsh ire , N e w p o rt Road, C a rd iff, Wales, U K . t D r. S. Speil Johns M anville Research and Engineering Centre, P.O. B ox 159, M anville, New Jersey, USA. Dr. V . T im brell Medical Research C ouncil, Pneumoconiosis U n it, Llandough H ospital, Penarth, G lam organ, Wales, U K . Dr. R. du T o it G overnm ent M ining Engineer's D ivision, Departm ent o f Mines, P.O. Box 1132, Johannesburg, South Africa. M r. W. H. W alton In s titu te o f O ccu p atio n a l M edicine, R oxburgh Place, E dinburgh EH 8 9SU, Scotland, U K . (Chairman) CONFIDENTIAL- In Re: Bickham. et al. v Met Life, et aL 9 AC/LA 007752