Document 6BdOVzeYDoygMwQkz1jxrVvj6

WRG 000663 \ RESEARCH GRANT APPLICATION TO W.R. GRACE & CO., CAMBRIDGE, MA ; FOR Epidemiological studies of the health effects of* exposure to tremolite in mining operations at Libby; Hdtetaria'* by J.C. McDonald, MD Professor and Director School of Occupational Health, McGill University IIMIPLAINTIFF'S EXHIBIT 12 August 1933 PLAINTIFF'S EXHIBIT Ice f-l--frCn t *' 2. 1. Background Vermiculite, a micaceous mineral which . expands on heat treatment has many uses in construction industries, agriculture and packaging. The largest known, vermiculite deposit, at Libby, Montana, has been commercially mined since 1923. At. first., it was on' a __yery ,, small scale but, i after.. .whan merged ,to form the Zonolite Company, production increased: 20,000 tons were shipped in 1940, 150,000 tons in 1950 and about 200,000 tons annually, since 1972. The Libby deposit is mined using the open pit mining technique incorporating rubber-tired loaders and trucks for both ore and ^ waste removal. Wasteis discharged at the perimeter of the mined area while the ore is hauled to a transfer point for blending and wet beneficiation. During early years of the operation, all functions of mining and milling were performed in a dry state, resulting in very dusty conditions. A series efprocess'improvcffgilf'g resulted in present mine personnel operating fron^^CI>gBrnWKasiiifc air controlled cabs and a totally wet beneficiatlon process the mill by 1974. Upon completion of the wet beneficiation process, vermiculite concentrate is graded into five size fractions before shipment. It has been known that heavy contaminationS^tl^fcTfNMlltm1*' y is present, averaging 4-5% of the ore mined*Trifnlltatfrilttiii' > has no - commercial use, is a fibrous mineral of thc^ampfclbolt series. Other members of the amphibole family include and amosite which are known to cause pulmonary fihrmii nnri mnllgnaiiL disease. Few observations on the health effects of tremolite in man have been made. Cohort-mortality studies of s tremolitecontaining talc mine in New York State showed an excess of pulmonary disease and -lung cancer and two cases of malignant mesothelioma (1). In 99 cases of malignant mesothelioma with matched controls, four cases with more than 10 million fibres of tremolite per g dried lung were observed compared with one control. The comparable figures, in cases and controls, for other asbestos fibres were as follows:- chrysotile 39:33, amosite 12:1, crocidolite 9:0, anthophylite 2:0. (2). In lung tissue from chrysotile -^miaerss and millers the quantity, of tremolite has on average r^been 'fourid^ to be similar to that of chrysotile although, only a minute frmccion 3 \ of the asbestos fibre mined (3--4). Satisfactory explanations for this observation are not yet forthcoming but it may be noted that the risk of malignant mesothelioma is low in the production and manufacturing of chrysotile but high with crocidolite and amosite (5). Experimental studies in nnlmslT hnirn rtsannnrrstad i that the carcinogenic potential of tremolite is aimilar to^Ghsea of other fibrous amphiboles <6). Some pulmonary disease was first noted among LHby ,ea^ldymss in 1959 .and, after W.R. Grace acquired the company in 1963, annual X-ray of employees was started. In the 1970's, pulmonary function tests were introduced and later a respiratory disease questionnaire. Efforts made by the companyto investigate pulmonary disease among workers included the search for death certificates for all known deceased employees. Individual exposures in terms of duration and dust 1 concentration were also estimated. Intensive efforts to further reduce exposures were made and a vigorous anti- smoking campaign was instituted to attempt to reduce the risk. It was recently., observed that there was an apparent excess of I respiratory cancer: 16 lung cancer deaths and 2 from malignant mesotheliomas in a total of 109 deaths. This information was reported by the Company to'EPA on March 24, 1983. ' In 1981, NIOSH expressed the wish' to investigate the health of employees in the industry and the company offered their collabora tion! ' Protocols .were developed by NIOSH for: ! 1) morbiditystudies using available x-rays, tests and symptom questionnaires.2 lung function 2) a mortality study of all persons employed one year or more, 1940-1969. , This proposalwas presented in February 1982 and it was then agreed that the company might also undertake their own studies but that all information should be shared. NBgsj'W6tntlyMBWif has indicated their intention to Include j^r|MTSon^sRHSW|)^Sfetl in their mortality stmdies^ They do not expect to complete ' the work before the end of 1984. 5. 2. Objectives The purpose of the research program described below is to complement the NIOSH studies in four ways:- a) by obtaining a more rapid indication of the extent of any T occupationally related mortality, in particular of lung --*cancer^^T!esothelioma or pulmonary fibrosis, with ecstimatpri exposure-response relationships. b) by checking that the findings in exposure-response obtained from the extensive radiological study by NIOSH, based on selected routine X-rays from current workers, are borne out by films of good quality taken by a well standardized modern technique from both current workers and a defined sample of ex-employees. c) by studying the relationship between past exposure and the same time confirming that there are no significant amounts of other minerals present- "particularly in cases of mesothelioma. d) by evaluating the use of ferruginous body counts in sputum as an objective measure of accumulated past exposure to amphibole fibre (in this case, tremolite). If proved valid. .could--have--wide--application--in--pre employment screening,------in----- epidemiological-----Studies and----- In-----asseisirig attributability. 3.1 Cohort study The cohort will" comprise all male employees with a record of employment for one year or more who were hired before January 1st, 1963. `There are 419 men who meet these criteria, 11 of Whom were first employed before T940. ' Four of these men left in 1940-45; the remaining 7 were ^long-term employees. Using company records all jobs in which "the subjects were employed ho -iriAnt-ified. -For each . _iob- exposure, estimates , will, be-- ----made year by' year. This work will be undertaken by Dr Sebastien (see 3.5 below). --. The vital status of each member of the cohort, . on July 1st 1983, will be sought. Excluding those for whom death certificates have already been obtained, enquiries will be made through other employees, friends and relatives. These inquiries will be made mainly by Earl Lovick who will state that the company is assembling statistics about all past employees. In addition, names and dates of birth will be submitted to drivers' licence bureaus . in states where the subjects may be living. Other possible sources nf -- i-nfannacion-- are ..electoral--liste?----local--feexet-ion- files--end- ------ :------- the--U.S. -Post Office. For those reported to be alive, place -- of residence with address or telephone number will be sought. If no certain information is available, the subject will be contacted .personally by" telephone _or mail. For' those reported as dead; the place and date of death is required. - -- When other- methods of tracing--ha vo fai led,--cases - -will -be submitted to Equifax, a company which provides credit information and also offers tracing services. 7. Upon being informed of a death, data will be submitted to State Vital Statistics Departments and a copy of the death certificate- sought.. If the death was not registered in the state of last residence, or the death occurred after 1978, the certificates will be obtained from the National Center for Health Statistics. Failing this, the cause of death will -be sought from the hospital where the death occurred. Finally; the causes of_death-, will*, be coded--.fay a qualified--nosologist--using -the 8th revlaiCF of,* the ICD. The data will be compiled on magnetic tape in three files including: 1) date of birth, work history (by numbered jobs), vital status and date and cause of death, for all cohort members. 2) exposure estimates by year and numbered job. 3) death rates for white males by cause, age and quinquennium __ for (a) Montana and (b) USA. "._ ________ In line with our usual practice, the statistical analyses will be of tjuo kinds. First, a man-years life-table analysis will be made in which observed numbers of deaths by cause are compared with those expected from (a) Montana and (b) US rates.. From this SMRs will be calculated for the main diagnostic categories -in relation-"to-^-estlmated' or fibre concentration (see 3.5 below)I A case-control 'internal' analysis will follow in which relative risks by exposure group are estimated ..from the overall."experience of the- cohort. To the extent that smoking histories are available, we shall also try to assess separately the contribution of smoking and tremolite. exposure on the occurrence of lung cancer. 3.2 Studies of mineral fibres in lung tissue Material for study will be gathered from two main sources;- 1. Cohort deaths to July 1983 -_ In all cases in which an autopsy was reported on the. death jertifirae ne" shall "T'Uuimuhicatfi "Vi Ch""'the neaa oi Ene department of pathology and request some lung tissue if available. For studies of lung tissue our order of preference is as follows: 1) whole lung 2) sagittal section of lung (about 1 cm thick) 3) pieces of lung tissue 4) paraffin blocks of tissue. For cases where the question of autopsy was not clear or in which a thoracotomy had been performed an enquiry about lung tissue will be made. 2. Non-cohort deaths to July 1983. Systematic efforts will be made to obtain lung tissue from autopsy or surgery from any other deceased ex-employees. After July 1983, continued `efforts will be made with the collaboration from pathologists at Kalispell and Spokane to encourage appropriate consent to autopsy in ex-employees to' obtain whole lung or sagittal sections... _-- -- --- -- - -- Electron microscopic studies on the samples collected will be made by Dr Sebastien to quantify mineral fibres by type, size and topographical area of lung in relation to estimated pxpngnrp. _ 3.3 Radiologic study To obtain reliable results with reasonable economy the radiological study (and related analyses) must be based on a I  *. .-,-v r* *.`W ^ 9. relatively small but well defined group of. .subjects. Current' employees are-X-rayed annually at LibbyHospital .and it is important that the resulting films should be of good- and even quaiity. . The' radiologist. Dr- Tyler Gill, has new -equipment and we -shall discuss with himthe use of some widely accepted and well standardized technique - for survey ' radiography ...such as, that _.recqmmendedl jito_ the International Labour Office--(-7).-"This `Will-- enable--all''films for our purposes to be taken at Libbyat least extracost. Subjects for study should then comprise a) all current male employees and b) all living members of the mortality cohort resident within - say 3 hours travel time from Libby Hospital - about 300 in all. ; We suggest that arrangements be made by Grace to have the films taken at company expense, if possible by the end of 1983. The^ nature and purpose of the study should be made clear and, so far as this research is concerned, participation is voluntary. The current employee sample will provide information mainly on the effects of the relatively low exposure of the last 10 years _ and .will provide a basis .both fpr.. comparisons with persons more heavily exposed in the past_. and.. .for. -future., observations. . The ex-employee sample will show the nature of long, term effects across a wide range of exposures and help provide a total picture of the health^-of- the cohort. We do not believe that the imposition of a geographical (travel time) limit in selecting' the sample will introduce important bias. - - Assessment ~~of~ thF' films ~ ~wiIT^"be~whoTTy rh* r;pnngi of the McGill team. For this purpose about 50 chest radiographs of similar quality and appearance will be added to the series from unexposed persons working in and around Libby. The complete set of about 350 films will be arranged in random order, labelled to obscure identification and allocated a serial number in preparation for classification into the 1980 IL0 International system by 10. three experienced survey readers. We would propose to invite Dr John Gilson r(formerly director of.' the MRC Pneumoconiosis - Unit, Cardiff), .Dr Robert.Jones (Tulane University) and another radiologist of international standing, to attend .la ...3-day . reading.-, session . probably' at McGill , in. February/March 1984 for this .purpose. The -assessments --wilt---be made independently--<+,*> .... averaged. - . \ - -jr _ The data analysis, again focusing on exposure-response, will examine the prevalence of radiographic changes - pleural and parenchymal - in relation to accumulated exposure (see 3.5 below) with allowance so far as possible for age, time since first exposure duration of exposure and smoking habit. Secondary analyses. The results from the most recent routine pulmonary function tests and respiratory symptom questionnaires will be analysed in relation to the radiographic readings, age _____ and smoking habit for degree of correlation. These "findings ___ will help the Company _ta evaluate--its---present--health "monitoring procedures at Libby. . " . 3.4-,. Sputum study " ......... 1 This investigationwill be. confined to current workers. During Dr Sebastien's visit to Libby in October, '1983 (see 3.5) ------- he -will- arratTBg^^to" ~se.eZ511.rmaIe -emplovees^and--explain--the--purpdse---------- of the study. He will provide each of them with three small plastic containers containing some preservative fluid and instruct them on how to collecttheir sputum at home onthree consecutive days. So far as possible, all employees will be persuaded to participate but they will be quite free not to if they so wish. When all specimens^ are collected they will be brought back to McGill by Dr Sebastien or by some other secure means. 11. I In the laboratory the three samples from each, man will be pooled" and -the volume measured;- After "homogenization-glides---- ^^ -- will be; prepared . for analysis by Dc. Bruce .'Case for the presence .. or absence of true sputum and for cellularity but _not for evidence of malignancy. .Half of each sample, will then" be digested ~andan estimation made. of . ferruginous, body . (FB) content by_ opticaLt. _Jmicroscopy.. A -proportion "of ~ the ...remaining . half samples wjjj~ ^1 r- be further analysed by electron microscopy for fibre identification. It is expected that almost all the FBs will have a tremolite core; if this is not so, the electron microscopic work will be extended as necessary. . -- Statistical analysis of the laboratory test results will .. aim to determine the relationship between the tremolite FB count, standardized for volume and cellularity, and work history, taking note of time since past exposure and accumulated exposure In fibre years. 3.5 ' Exposure-estimates A limited quantity off information is available* biv ' the pair1* exposure of workers at Libby mine. Environmental ~ measurement! using #. midget* .impinger were made by Montana Health 'llapbrlWII on .a ::^|jpber of occasions during the period 1941v*thttmth.-HHMn In 1968, MESA carried out- midget impinger and :menUiraua filter^ mpflgirpnnnr; HHp hy g-irfo __Since_____ rhen t rpgnlar personal apri frequent stationary membrane filter measurements have been made.. --- In 1956, impinger counts of up to 80 mpcf were reported. There was then a gradual reduction in dust levels which became dramatic with the introduction of wet milling. Further engineering improvements have since brought down average fibre counts to just below 0.5 i/ml. 12. In order to estimate individual exposures all jobs listed : . ** in employee work, records will be identified and the best estimates possible made for , the. period. 1937--1963. . For this, use will be made- of information assembled by the company, measurements made Montana State, Health Dept, MESA, and measurements newly made "ky ,,p.f Sebastien together with his best evaluation of data available.. Having'-regard - for. the ;fact that the most significant exposure took place at , a time whenaonly dust counts were .. am) few at_ that, our primary analyses may well be .made in relation to dust. However, we shall then repeat the analyses using the best estimates we can on conversion ratios. f 13. 4. ' ;. Personnel The project will .be- under the -general, direction of Dr*-J.C. McDonald, in collaboration "with Dr :A..frr`McDonald, and ;Dr P. SebastienV. .Dr . / A.D._. McDonald will be responsible ..for .the cohort study .of : mortality - and' for 'the identification, .`and- collection of autopsy "matoemul , Di,*''SebdSEffiil*"I(J? "all enyironmentar"^ro5~"laboratory"*-work, and Dr B. Armstrong (who joins the School staff this month) for statistical analysis. The assistance of Dr J. Birke is required A for specific aspects of the mortality and radiologic studies and Dr B. Case (Assistant Professor of Pathology of McGill) for cytological analysis of sputum samples. The project has been discussed with Mr. Robert Glenn, Director of the NIOSH laboratories in Morgantown and it was agreed that an 'observer' from his staff would be appointed to our research group, to maintain close contact between their studies and our own. A reciprocal arrangement will also be made. 14. 5. ... Timetable - We propose, that the project begin formally on September 1st, 1983 (or its soon, as approved) and- that the data collection and basic. analysis be completed if possible in one calendar year. We - shall -make every effort, to achieve this target but cannot gilaranb.ee '^fco1 -"do ~so "*s?nc?"1l?e*^puT3""T?*"3eT5yed by factorj^Hbeyohd our' control. -Progress might be usefully reviewed at about 4 monthly intervals. Concise progress reports will be prepared at these times sufficient to permit full discussion if necessary. An approximate timetable is set out below showing the deadlines for each main component of the proposal. Cohort Autopsy Radiology Sputum 1983 Jul cohort defined Aug Sep ' - '----- .' r-. . --Oct ------------ ------------------ Woy Dec _ tracing complete collect samples x-rays completed Environmental review -data 1984 ------- Jan certificates obtained Feb'*- Mar -,"v.' - specimens collected Apr analysis May x-rays read lab work completed exposures estimated Jun Jul Aug et seq. analysis analysis analysis Preparation of reports for publication f r4 ... - .6. '. Budget (in US$) . 'All figures are .estimates 6-1" Salaries * . ' v Technician ... (1 year full-time) Clerk..-;. ^ (1 year full-time) " ' c / Statistical . _ clerk/programmer (1 year half-time) ;16,000 ^12.000, 8,000 d) Fringe benefits 16% 36,000 5,760 Sub-total (a-d) 6.2 Honoraria for x-ray readers 6.3 Laboratory expenses incl. tissue analysis, sputum analysis and cytology 6*4 Office expenses incl. phone, photocopying, typing, etc. and conduct of x-ray reading session 6.5 . Travel.and subsistance expenses incl. visits to Libby, Cambridge, Morgantown, etc. and travel costs for x-ray readers 6.6 , Miscellaneous fees and expenses incl. Equifax services, tracing expenses, fees to state departments of vital statistics I 41,760 3,000 8400._ 4,200 11,000 2,000 <**- .* . .. .. .* 6.7;. Statistical analysis 'incl. coding, computing, programming, etc/*. 6.8 . Equipment grant . ~ v."-4 -. *"* toward cost of new EM equipment.' v` . -----'*> ' .* . rr;'.'.:".' *..**,*.' 6.9 McGill indirect costs 2% on item 6.5 50% on rest (excluding 6.8) 220 31,680 sub-total Estimated total: 16 - 4^000 :.,24,000 31,900 130,260 -Please note: 1) that the budget does not include the cost of the X-rays and related expense for current and past employees, ' 2) that all figures are estimates and freedom to transfer expenditure from one heading to another is required. . ' r-.. . f 17. General conditions This application 'is. subject to certain..conditions:- that, as required by a duly constituted ethics committee at McGill, both management and employees shall, receive ^an^account^Jo^^the^werall^indings^and^^ach^jgersonj^examine^ (or-- his -physician) a confidential report on the ^-results of the chest X-ray; Should any finding of clinical relevance be discovered by sputum analysis, this will also be reported to the subject or his doctor. that the protocol is formally approved by the local trades union representing employees at Libby. The Union President, Mr. R. Wilkins, agreed to the proposal at our meeting on May 16th but we would require written confirmation. that we have the - right to publish the flndings :hKM^yn .research .. in (an) _nuaropciaj;e_scientijic .^jouci given the Company "reasonable time (at least .90 dye), tae comment. s.-- 18. .8 References 1., A' .Kleinfield M, Messite -J.,-^Kooyman Zaki.. MH..(1-967).. Mortality among talc miners and millers in New York . State.. ... Arch . 'Environ Healthy 14: 663-667. . ;_v.- 2. McDonald AD, McDonald. JC, Pooley FD (1982). Mineral content. '*; of lung in mesothelial tumours in North America - Ann-'-Ocdup. - Hyg. 26; 417-422. . . - r - ' cn---%= 3. Pooley FD (1976). An examination of the fibrous mineral content of asbestos in""lung "tissue from the Canadian chrysotile mining industry. Environ Research, 12: 281-298. 4. Rowlands N, Gibbs GW, McDonald AD (1982). Asbestos fibres in the lungs of chrysotile miners and millers, a preliminary report. Ann Occup Hyg, 26: 411-415. 5. McDonald JC (1983). Exposure response, fibre type and industrial process. Proceedings of World Symposium on Asbestos, Canadian Asbestos Information Centre, Montreal, pp 29-48. 6. Wagner JC, Chamberlain M, Brown RC, Berry G, Pooley FD, Davies R, Griffiths DM (1982). Biological effects of tremolite. Brit J Cancer 45: 352-360. 7-r-------Guidelines for the - use of ILO Classification of radiographs of pneumoconioses. Revised edition (1980) Appendix A. Occupational Safety and Health Series No 22, ILO, Geneva,