Document x59NOpBkjgNVjD4grmaxy5jq1

FILE NAME: WR Grace (WRG) DATE: March 1 , 1986 DOC#: WRG341 DOCUMENT DESCRIPTION: 1986 Cohort study of mortality of vermiculite miners submitted to EPA CO DIN G FORM FOR S R C INDEXING REV ISED 10/15/86 COHORT STUDY OF MORTALITY OF VERMICULITE MINERS EXPOSED TO TREMOLITE WITH COVER LETTER DATED 030486 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET Health, Safety and Environmental Service' m Industrial Chemicals Group G R fiOE W.R, Grace & Co. 62 Whittemore Avenue Cambridge MA 02140 (617) 876-1400 4 March 1986 Document Control Officer Management Support Division Office of Toxic Substances U .S. Environmental Protection 401 "M " Street, S.W . W ashington, D .C . 20460 Agency iE Hr 030,-041-3 29- 2^ 8 0 / ^ F i^o P & EPA-CTB 000401449M GDGH0144'it1 Subject: Document Control Number 8EHQ-0383-0473 T he McGill U n iv e rsity stu d y of the health effects of exposure to tremolite at the W. R. Grace 6 Co. (Grace) mine and mill in Lib b y, Montana, has been completed. Actually, independent but cooperative studies were done by the National Institute of Occupational Safety and Helath (N IO SH ) and the McGill team which included D r. J. C. McDonald, D r. A. D. McDonald, and D r. P. Sebastien. Combined results were presented ve rb a lly at a September 1985 conference on dust-related lung disease in Cam bridge, En glan d. The attached documents by the McGill team have recently been finalized and submitted to the B ritish Journal of Occupational Medicine for publication. N IO SH has just completed their report and will be sending a copy directly to the EPA. Somewhat different techniques were used by the two study gro u p s but the resu lts were sim ilar. The relatively small differences are explained in the attached McGill reports. We believe that these reports contain all informa tion requested in Fran k B. K o v e r's letter of A p ril 25, 1983. However, we can make members of the McGill team available for clarifications if necessary. Please note that these are pre-publication documents and under normal circum stances are not distributed prior to publication. Sincerely yours, H. A. Eschenbach, Director Health, Safeiy & Toxicology HAE/cs attachments E227 00002 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET COHORT STUDY OF MORTALITY OF VERMICOLITE MINERS EXPOSED TO TREMOLITE J.C. MCDONALD A. D. McDo n ald B. ARMSTRONG and P. SEBASTIEN SCHOOL OF OCCUPATIONAL HEALTH McGILL UNIVERSITY, MONTREAL, CANADA 00003 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 2. 1. Abstract A cohort of 406 men employed before 1963 for at least one year in a vermiculite mine in Montana, was followed until July 1983. The' vermiculite ore as fed to the mill contained 4 - 6% of amphibole fibre in the tremolite series. Vital status was established in all but one of the 406 and death certificates obtained and coded for 163 of the 165 men who had died. Compared with US white males, the cohort experienced excess mortality from all causes (SMR 1.17), respiratory cancer (SMR 2.45), non-malignant respiratory disease (SMR 2.55) and accidents (SMR 2.14). There were 4 deaths from malignant mesothelioma (proportior al mortality 2.4%). Compared with Montana death rates, the SMR for respiratory cancer was somewhat higher (3.03). Man-year analyses of respiratory cancer and estimated cumulative exposure gave a relation ship which did not depart significantly from linearity. The results of this and case-referent analyses indicate an increased risk of mortality from respiratory cancer in this cohort of about 1% for each fibre year of exposure. In relation to estimated exposure, the mortality experienced by the cohort from both lung cancer and mesothelial tumours was higher than in chrysotile mining. ------------------- '---^ ----- :------ ------------- --- !--1---- ' 00004 f |_____ ____________ ___________ 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 3. 2. Introduction In April 1983, we were invited by W.R. Grace & Co, owners of a vermiculite ' mine in Libby, Montana, to investigate the health of their employees. Morbidity and mortality studies in the same population had been initiated by NIOSH in February 1982 but, because of the jurgent decic.ionsjwhich faced them, the Company wished to have an independent inquiry as quickly as possible. Having assured ourselves that NIOSH and the employees* union had no objection to parallel and complementary studies, and indeed welcomed them, our research proposals were finalized and accepted in August 1983 and we began work in September. Our studies had four components: a cohort mortality study (described in this paper), a cross-sectional radiographic survey, an investigation of asbestos bodies in sputum, and an electron-microscopic analysis of lung tissue samples at autopsy from ex-employees. Findings from the last three studies will be reported separately (1, 2, 3), as will those of NIOSH. Although the NIOSH inquiries and our own were designed, conducted and analysed quite separately, we discussed and compared our data and methods at every stage. This was a valuable exercise; unnecessary differences and discrepancies were eliminated and the reliability of both sets of results increased. Concern for the health of workers in this mine stemmed not from exposure to. vermiculite, a micaceous mineral 'for which no adverse effect is suspected, but from the fact that the ore body is contaminated with fibrous amphibole deposits in the tremolite series. Fibrous tremolite and related minerals fall within the definition of asbestos (4)' but have very limited value and are produced only in some very small mines in Northern Italy. On the other hand, they are common contaminants in various mining operations, notably the chrysotile mines of Quebec and certain talc mines in New York State. Other members of the amphibole family include crocidolite and amosite which are known to cause pulmonary fibrosis, lung cancer and malignant mesothelial tumors. Existing evidence 0 2 / 1 4 / 1 9 9 6 EPA T3CA DOCKET 00005 4. suggests indeed that most occupationally-related mesotheliomas are caused by amphibole fibres and few by chrysotile (5,6,7). The experience of men in the Libby mine exposed only to the tremolite group of fibres was therefore of practical concern and scientific significance. Few observations on th e . health effects of tremolite have been made.Cohort studies of employees of talc mines . in New York State, some of which may contain fibrous tremolite, showed an excess or pulmonary disease and lung cancer and one or two cases of malignant mesothelioma (8,9). In an autopsy study of 99 cases of malignant mesothelioma and matched controls, four cases with more than 10 million fibres of tremolite per g dried lung were observed compared with one control (10). The comparable figures, in cases and controls, for other asbestos fibres were:- chrysotile 39:33, amosite 12:1, crocidolite 9:0, anthophyllite 2:0. . In lung tissue from chrysotile miners and millers, the quantity of tremolite appears similar to that of chrysotile, although only a mini ;e fraction of the asbestos fibre mined (11,12). In a study of six mesothelioma cases from the Qubec chrysotile mines, tremolite was the predominant fibre found in the lung tissue at autopsy (13). Experi mental studies in animals have demonstrated that the carcinogenic potential of tremolite is similar to that of other fibrous amphiboles (14). Evidence of pulmonary fibrosis was first noted in an X-ray survey cf Libby employees in 1959 and, since Grace acquired the company in 1963, employees have been X-rayed annually. In the 1970's, pulmonary function tests were added and, later, a respiratory symptom questionnaire. Intensive efforts were made to minimize exposure and a vigorous anti-smoking campaign was instituted to further reduce the risk. Efforts made by the company to investigate pulmonary disease among workers included the search for death certificates for all known deceased employees. Individual exposures in terms of duration and dust concentration were also estimated. An analysis of these data revealed 16 lung cancers and 2 malignant mesothe liomas in a total of 109 deaths. This information was reported by the company to the US Environmental Protection Agency on March 24, 1983. A preliminary case-control analysis of these data by ourselves indicated that the lung cancer risk was probably related to cumulative exposure. 00006 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 5. 3.1 The production process - Vermiculite Is a mineral derived from geo logical transformation of trioctahedral micas (15). On heating, the material expands approximately 15 times in volume and acquires useful properties. Expanded vermiculite is mainly used as an insulator against heat and noise in the construction industry and also as an absorbant low density filler and chemical carrier. Of the 325,000 tons of vermiculite concentrate (before expansion) used in the USA in 1984, . 54% came from the Libby mine. According to legend, the vermiculite mountain in Libby was discovered in 1913 by Edward N. Alley: walking in a short tunnel in search of metal deposit, the flame of his mining candle came in contact with vermiculite and the immediate transformation by heat attracted his attention. Commercial exploitation started in 1923. Libby production, initially low, increased from 20,000 in 1940 to 150,000 tons in 1950 and 200,000 tons in 1970. At the present time, mining is conducted on benches or levels that ^ extend laterally from the surface to more than 300 vertical feet below the original surface of the mountain. Although equipment has changed over the years, ore has always been extracted by the classical technique of drilling, blasting, loading (with shovels or front-end loaders) and hauling to the mill or transfer point. Drilling was considered the most dusty operation and, in 1970, new drills with baghouses were introduced. After removal of coarse rock, the ore is blended and fed at con trolled rates to the top of the mill. At this point the granules are about 1 cm in diameter and contain approximately 20% vermiculite. Accom panying minerals are augite, biotite, calcite, diopside, hornblende, magnetite, quartz, sphene and tremolite-actinolite (16). Milling takes advantage of differences in particle shape to separate the thin flakes of vermiculite from the blocky waste particles. The finished concentrate in 1984 contained 80-95% vermiculite. Before 1954, the milling was basically a dry screen process. A second mill, operating a wet process, was added in 1955 to 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00007 6. accomplish the first stages of separation. Work in the dry mill was very dusty but became much cleaner after 1965 when ventilation equip ment was installed. In 1974, for hygienic and technical reasons, both dry and wet mills were shut down and ore was processed in a new mill built nearby which operated on an entirely wet process in which separation was made by vibrating screens, roll- screens, Humphrey separators and flotation. The new wet mill operates continuously, producing 1,100 tons of concentrate each day in 1984; this is then dewatered, dried and hauled to the screening plant. AID the mill water is reclaimed after clarification in a tailings pond. The screening operation separates grades of vermiculite con centrate, differing in particle size and industrial application. The tech niques for handling and shipping concentrate at Libby have been changed several times with the object of controlling dust exposure. At present most of the concentrate is shipped by rail, the loading station being equipped to reduce dust exposure; bagging is still used to a small extent. 3.2 Study group - Our cohort comprised all male employees with a company record of employment starting before 1 January 1963 and a net period of at least one year. These criteria were met by 406 men. Twelve were first employed before 1940, and the remainder there after. The. vital status of each man on 1 July 1983 was sought. Inquiries were first made of relatives and friends by : recently retired long-term company employee. For all those reported dead, the date and place of death were investigated; for those reported alive, the address and telephone number were requested. In cases in which these inquiries failed to produce a satisfactory result, information was submitted to drivers' licence bureaus. Finally, the results of searches of social security files for NIOSH were consulted for those men who could not otherwise be traced. The number found to be living on 1 July 1983 was 226 and 165 were reported dead. A further fourteen men could only be traced through social security files; these men were known to be living on 31 December 00008 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 7. 1981, but their subsequent status was not established. . They were included in the man-years analysis until the date at which they were lost to view. Death certificates were sought in the state in which each of the 165 deaths was thought to have occurred. Copies of death certificates were obtained for 163 men. The registered cause of death was coded by a single qualified nosologist according to the eighth revision of the Inter national Classification of Diseases. The causes of death are shown in Table 1. 3.3 Mineralogy - It is well established that the vermiculite deposit in Libby is contaminated by asbesut'orm fibres (17). Their presence in airborne dust was first mentioned in 195S in the report of an industrial hygiene survey by the Montana State Board of Health but only very recently has further information become available on the. nature of Libby fibres (16). A systematic study by analytical transmission electron microscopy of airborne fibres collected on membrane filters in various locations of the mine and mill is now in progress. Preliminary findings on samples from the wet mill indicate that fibres exhibit several morphologies. They may be straight, with uniform diameter, have a lath or needle shape or be curved; they may be found intermingled with other platy particles (see Figure 1). So far, the ranges for diameter, length and aspect ratio are 0.1 - 2 pm, 1 - 70 Um and 3 - 100 respectively. A fairly high proportion (62%) of fibres have been found longer than 5 pm.. Comparison of electron and optical microscope counts shows that about a third of the total airborne fibres are detected by the optical technique used for measuring exposure to asbestos at the work place (18). Elemental chemical analysis of individual fibres by energy dispersive spectrometry (19) yielded unsuspected and complicated results. Although the chemistry of many fibres was compatible with minerals of the tremoliteactinolite series, the sodium content of some was too high to meet the 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00009 8. criteria for tremolite according to the classification of the International Mineralogical Association (20). Some sodium-rich fibres either displayed no calcium reponse (with both B sites in the theorectical formula of amphiboles occupied by sodium), and so could be called magnesio-riebeckite, or displayed an intermediate calcium Response (sodium distributed between A site and B site) and could be called richterite. X-ray diffraction analysis of Libby samples by Atkinson et al (16) detected what they called "sodium tremolite" but it was not stated whether it was in fibrous form. They also observed by optical microscopy that comminution of massive amphibole crystals produced cleavage fragments resembling fibres. These observations indicate the complexity of the Libby situation; the airborne fibres are probably a mixture of different types of asbestiform and massive amphiboles. In addition, there may biso be some, exposure to quartz since this mineral was identified in some ore samples (16) although not reported in air samples taken in government or company surveys. 3.4 Exposure estimates - Regardless of their nature, we had to estimate for each member of the cohort the cumulative fibre exposure as measured by standard optical microscope technique (18) (the so-called 'regulatory fibres'). Work histories based upon 42 defined job categories were obtained from the company together with detailed information on the process, its changes with time and the introduction of control measures. Analysis of the process and observations made during two field visits (by P.S.) showed that the 42 job categories described the working operations, with good specifi city. Our general strategy for estimating cumulative exposures was a) to take maximum advantage of existing air measurements and b) to concen trate efforts on the past dry mill period (before 1975) when substantia! exposures occurred. Altogether, results of 1363 air measurements were available for the period before 1975. They were extracted from reports of surveys carried out by the company, the Montana State Board of Health, the National Center for Urban and Industrial Health and the Bureau of Mines. Efforts to monitor the work environment which .trior to 1967, were virtually restricted to measurements of dust concentration in the dry mill using the midget impinger method, increased substantially 00010 02/ 14 /1996 EPA TSCA DOCKET 9. in the 1970's with the introduction of the membrane filter method (21). In the entire period before 1965 only 48 environmental measurements were made; this increased to 385 for the period, 1965-69, and to 930 for the period 1970-74. Both static and personal sampling had been used. As most of the personal samples were short-term, they probably reflected ambient concentrations rather than time-weighted average exposures. A modified version of the exposure-zone concept (22) was applied in using air measurement data to estimate exposure. Bearing in mind that at any time, a worker is somewhere, doing something, we defined 28 operation-locations (Table 2). These were defined to ensure that every available air measurement could be unequivocally allocated. Information on location was used to classify static samples and that on operation to classify short-term personal samples. Operation-locations were further divided in time periods bounded by dates of significant change in process or in control procedures. In the calculation of cumulative exposure, grouped air measurement data were averaged using the technique of Oldham (23), which provides "a minimum variance unbiased estimate" of the arith metic mean in skewed log normal distributions. In the dry mill, midget impinger measurements were made in 1944,1956 and 1958 and much more regularly in the period 1962-69. High dust concentrations (38.9 mpcf geometric mean) significantly dropped by a factor of about 4.6 in 1965 after the installation of a major piece of ventilation equipment, known as the scirocco fan. There was no clear indication of further consistent decrease in concentrations in the dry mill after 1965 and concentrations were taken as constant. Measurements by the membrane filter method in the period, 1970-74, revealed a mean concentration of 22.1 f/cc. It was therefore assumed that the concen tration in f/cc for the period before 1965 was 4.6 times higher, i.e. 101.5 f/cc. Only two operation-locations were considered in the dry mill: dry mill working (except sweeping) and dry mill sweeping. Personal samples indicate that sweepers in the dry mill were exposed to concen trations about 20% higher. 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00011 ID. For the other operation-locations fibre measurements were available only for the recent periods. When the data were considered inadequate to describe past conditions, because of changes in process or control prac tice, arbitrary correction factors were applied. This was done after dis cussion in depth with company's representatives and especially with a pre vious manager who spent almost all his career in Libby and who had extensive knowledge of the operations. The estimated average levels of exposure at the 28 operation locations, 1945-82, are shown in Table 2. Recent values (1975-1982) were calculated in the same manner from data provided by NIOSH, where all available air measurements had been collected. As the company had introduced a systematic air sampling program in 1975, the number of measurements for this period was much higher than in the past. As these recent measurements had been made by long-term personal sampling, the operation-location model may be less appropriate since the same sample may .cover more than oneoperation-location. However, recent fibre counts were low so it is unlikely that this materially affected the accuracy of our cumulative exposure estimates. The work histories were available in terms of job category, not operation-location. We therefore used job descriptions to estimate for each job the period of time and the number of hours spent by workers in different operation-locations; the cumulative exposure was then calculated. Again, the help of company representatives made this possible. 3.5 Statistical analysis - The mortality of the total cohort was compared to that of US white males using the person-years at risk method to com pute expected numbers of deaths and hence standardised mortality ratios (SMR's). These computations were made using Monson's computer program (24), from which US national age-specific death rates, available to 1975, were also taken. Additional analyses of mortality from respiratory cancer were made using Montanadeath rates from published figures for numbers of deaths, together with appropriately interpolated estimates of population 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00012 11. from censuses. Respiratory cancer death rates for Montana were computed for the period up to 1978, and the US National rates for this cause updated to this year for comparability. Analysis of the relationship between mortality and exposure to fibrous dust was performed in two ways. Firstly, the exposure cumulated to the end of each month of each man's life, or until the end of 1982 for those who survived until then, was calculated. Person-years at risk were then divi ded into four groups according to cumulative exposure to fibres, and expected deaths and SMR's computed for each group. A linear relationship between SMR and cumulative exposure was then fitted using the GLIM program in the manner described by Hanley and Liddell (25). Secondly, relative risks were estimated from case-control sets chosen from within the cohort. Controls for each case were chosen as men surviving beyond the age of death of the case, who had been born and had started work at Libby mine within three years of the case. For each control,exposure was cumulated to the age of death of the matching case. Estimates of linear increase in relative risk {odds ratio) per unit exposure were made using the method of conditional likelihood. (26) 4. Results The mortality experience of the cohort as a whole is summarized in Table 3. Mortality for all causes was in excess of that expected for US white males by 24 deaths (SMR 1.17). The SMR for all causes rose from 0.79 for the first 9 years from first exposure, when 'healthy worker' selection effects would be expected to be strongest, to 1.31 after 20 years from first exposure. There was a substantial excess of deaths from res piratory cancer (SMR 2.45), from non-malignant respiratory disease (SMR 2.55), and from accidental causes (SMR 2.14). There was no evidence of excess deaths from cancers of non-respiratory sites. Eight of the non-malignant respiratory disease deaths were certified as due to pneumoconiosis (1CD 514 or 515). Of the 18 deaths due to accidental causes, five occurred while the men were employed at the mine and the other .th irteen a fte r they: had left. There were four deaths from 00013 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET . 12- mesothelioma; one was coded by the nosologist to respiratory cancer (ICD 165), one to pneumoconiosis (ICD 515), and two to neoplasm without specification o f site (ICD 199). Three of the cases were pleural and one peritoneal. In addition, there was one death certified as due to mediastinal cancer (ICD 163) in a man 9 years after first employment. At autopsy the pathologist did not consider this a mesothelioma. Using Montana death rates instead of US national rates reduced the number of respiratory cancer deaths expected from 9.41 to 7.60, inc reasing the SMR from 2.45 to 3.03. SMR's for respiratory cancer (using Montana death rates) by cumulative exposure are given in Table 4. It is reasonable to focus attention on the SMR's 20 or more years from first employment,when risk due to fibre exposure would be expected to be most evident. A linear relationship between these SMR's and cumulative exposure (see Figure 2) is given by the equation SMR = 1.52 + 0.011 f.y. or, expressed as a relative risk, RR = 1 + 0.007 f.y. Alternatively by forcing the line through SMR = 1 at zero exposure, the equation SMR = 1.00 + 0.013 f.y. was obtained. The observed deviation from linearity could be explained o by chance (X (3df) = 3.47) and the trend has high statistical significance (X (Idf) = 18.9, p <0.001). The constrained line may be interpreted to imply an increase in SMR for respiratory cancer of about 1.3% for each fibre- year of cumulative exposure. There is also evidence in Table 4 of excess mortality from lung cancer less than 10 years from first eniploymt.t. The two cases in the lowest exposure category muld not have been due to work at Libby. One was a man who was first employed at age 66 and died aged 69; the other joined at age 25 and died aged 28. The two other deaths in the short latency category were 8.9 and 9.1 years from first employment. They had both substantial levels of cumulative exposure (470 and 522 f.y.) so a causal hypothesis is less easily dismissed. Case-control analyses of exposure-response were carried out for the 23 deaths coded to respiratory cancer (ICD 160-163), the 8 coded to pneumo coniosis (ICD 514-515) and (with some overlap) the 4 mesotheliomas. Results are presented in Table 5. A statistically significant linear relationship was found between relative risk for respiratory cancer and cumulative exposure which is clearest in cases occurring 20 or more years from first employ ment (X (Idf) = 7.04, p <0.01). In this group the linear increase in relative risk is estimated at 1.0% per fibre-year (95% confidence interval 0.3 - 9.7). This relationship is described by the equation RR = 1.00 + 0.010 f.y. Although 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00014 13. positive relationships with cumulative exposure were also observed with pneumoconiosis and with mesothelioma, numbers were small, confidence intervals wide, and conventional levels of statistical significance were not reached. 5. Discussion . The cohort studied was not a large one but quite sufficient to demonstrate that the workers in this mine experienced a serious hazard from lung cancer, pneumoconiosis and mesothelioma. This was presumably attributable to the fibrous amphibole contaminant of the vermiculite ore and mainly to dust conditions prior to fS74,particularly in the dry mill. No precise comparison with the New York State studies can be made but the crude SMR's for lung cancer were similar, 2.4 in this study, 2.8 in the study by Kleinfeld et al (8) and 3.2 in that by Brown et al (9). Not suprisingly, the SMR obtained in the parallel study by NIOSH (10), 2.2,was very close to our own. In all these studies, cases of mesothelioma were reported. The findings in the NIOSH study, although close to our own, were not identical for four main reasons: 1) Their cohort was larger and included men first employed before 1969, but observation terminated 18 months earlier. 2) Their cohort was based on work history records, ours on computerized company work history files. Sixteen men (alive in 1981) who had started before 1963 according to the former probably more correct records had not done so according to the latter, and were thus not included in our cohort. Conversely, two men were included in the McGill cohort although their work history records indicated that they had started in 1963 - 3) Athough we used the same basic exposure data, we did not treat it or interpret it in exactly the same way 4) The same death certificates were coded by the same nosologist but with some differences. As a result of these various 14. Our analyses of respiratory cancer mortality in relation to accumu lated expsoure do not in themselves establish a linear relationship. But, given the findings iron) other asbestos-exposed cohorts (5), it seems reason able to expect a similar exposure-response pattern in this group also.- On that assumption, our findings suggest *that the observed slope (about 1% increase in lung cancer per fibre year of exposure ) is the same as that calculated by Doll & Peto (27) for chrysotile textile workers. This slope was substantially steeper than that estimated for Qubec chrysotile miners and millers (28) in whom the proportional mortality from mesothe lioma was also much lower. Having regard for the fact that a) the Canadian miners were-also exposed to tremolite fibres, albeit in very low concentrations, and b) tremolite is present at autopsy in lung tissue of these miners in similar amounts to chrysotile (12) and in higher amounts in cases of mesothe lioma (13), one is forced to question the relative carcinogenic potency of chrysotile even in the mines and mills where it is produced. The rarity of mesothelioma (1 case) in the South Carolina chrysotile textile plant* where lung cancer was in great excess appears to exclude any simple explanation based solely on fibre type per se. However, whereas the textile process - carding in particular - may well separate the chrysotile bundles into finer more carcinogenic fibrils, few of which reach the pleura, amphibole fibres ( including tremolite ) are much less susceptibl to longitudinal division but remain able to penetrate more deeply than chrysotile. For mesothelioma, penetration is the prerequisite.. For lung cancer, which is initiated in the airways, as indeed is asbestosis, length, thinness: and durability of the fibrils together wth tobacco smoke and perhaps other carcinogens are more important parameters than ability to penetrate. If a linear relationship between lung cancer risk and accumulated exposure be accepted, a 1% increase in mortality per fibre year has practical implications for control in this industry. At present airborne fibre concen trations, reported by the Company to average about 0.1 f/m! , the estimated risk of lung cancer over a working lifetime, might be increased by about 5%. However, this estimate is associated with considerable statistical uncertainty and could vary in either direction by a factor of perhaps two or three. 00016 0 2 / 1 4 / 1 9 9 6 EP TSCA DOCKET . 15. From the viewpoint of epidemiological methodology, it may be worth noting that the exposure-response conclusions from this study confirmed the preliminary case-control analysis of incomplete data made in 1983 men tioned in the Introduction. However, as exposure levels had been under estimated, the slope of the line proved less steep than it had then appeared. Rapid analyses of this kind (29) deserve to be used more often for imme diate assessment of occupational hazard. 6. Acknowledgements This research was supported by a grant to McGill University by W.R. Grace & Co., with whose help the cohort was identified and p<*st exposures estimated. We received assistance from several agencies in the follow-up and in particular we acknowledge the invaluable contribution of Mr. Earl Lovick in all aspects 'of the study. 00017 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET Table 1 Male deaths by age and certified cause Cause of death (ICD code) Age at death (years) <45 45-64 265 All causes 11 79 75 Malignant neoplasms: Larynx (161) . Trachea bronchus & lung (162) Pleura & mediastinum ? (163) Oesophagus & stomach (150-1) Colon & rectum (152-3) Other abdominal (154-9) Other (140-149, 160, 164-208) . Heart disease (390-429) 0 1 0 0 0 0 . o 1 0 0 16 4 2 0 1 1 2 0 2 1 8 5 21 32 Respiratory tuberculosis (010-018) 0 1 0 Other respiratory (480-519) 0 9 12 Cerebro-vascular (430-458) 0 4 7 External causes: Accidents (E 800-949) Other E(950-998) 4 8 6 2 2 1 Other causes 2 3 5 Causes not known 1 0 1 Total 165* 0 21 2 2 2 3 13 54 1 21 11 18 5 10. 2 * including 4 deaths from malignant mesothelioma coded ICD 163(1), 198(2) and 515(1) _______111/ ................................................ 02/14/1996 P illi EPA TSCA DOCKET 00018 vWMxWsBki;, Table 2 Estimated average prevailing fibre concentrations (f/ml) at main work location-operations; 1945-82 1950 Mine pit-working -drilling Tails belt operation Transfer point Dry mill -working -sweeping New wet mill Mill lunch room Service area Skip boot River station-dock -office Railroad by-standing 36.0 * Concentrate-loading 24.0 * -bagging -hauling Testing-laboratory - -van . 101.5 124.9 I960 . 2.5 12.5 7.9 2.8 * * .1970 * 22.1 27.2 ' * * 5.2 * * * * * 1980 . 0.6 0.8 0.7 0.6 * 3.9 * 1.5 * 7.0 1.0 68.8 * * 2.4 * 0.5 , * 2.0 * 0.9 * 0.2 * 15.0 * 2.0 ' * 0.6 12.0 4.7 18.0 * 6.0 15.0 * 9.0 24.0 5.4 2.9 1.0 * 0.7 * 0.2 * 1.2 # 0.5 * 4.8 * 0.2 * 5.5 * 1.2 * 0.4 * 0.6 * 0.5 Fibre concentrations were taken as constant for the relevant periods at the following locations: bus transfer U.2), mine lunch room (0.9), mine office (6.5), screen p'?nt (0.5), verxite plant (6.0), office building ( <0.04), laboratory (0.2), old wet mill (5.1). \?o available for figures in italics. Asterisks delineate the time periods over which the estimates apply. IA 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET Table 3 Deaths and SMRs by cause and time since first employment ( Reference ; US white males) Cause of death ICD (8th rev) All Causes Malignant neoplasms Respiratory Abdominal Other Circulatory disease Non malignant Respiratory disease Externa! causes Accidents Other 160-163 150-159 390-458 460-519 . 800-949 950-998 <10 0 SMR 17 0.79 Time since first employment (y) 10-19 220 0 SMR 0 SMR 45 1.11 103 1.31 Complete cohort 0 SMR 165 1.17 4 5.02 (1.35-12.85) 1 0.86 ' 0- 3 0.31 4 1.66 '.45-4.24; 1 0.44 2 0.69 20 0.93 15 2.42 23 2.45 (1.35-3.99) 5 1.11 7 0.88 11 1.83 13 1.26 42 " 0.97 65 0.87 0- 7 3.36 14 5.30 21 2.55 5 1.80 1 1.02 4 1.46 3 2.22 9 3.11 1 0.72 18 2.14 5 1.28 . o - : to 95% confidence intervals in parenthesis Table 4 Deaths from respiratory cancer (ICD 160-163) SMRs and.cumulative exposure (Reference : Montana males) Cumulative Exposure ( fib ml"1'y*) Mean net length of service (y) Mean concentration (fib m f ) Mean cumulative exposure* (fib m f 0,. <25 3.0 5.8 12.5 25,< 200 13.8 10.0 77.3 200, <500 11.0 49.7 332.4 500 16.0 64.2 836.1 All 8.7 ` i17.6 144.6 Time from first employment (y) 0 2 0 1 SMR 6.67 0.00 9.09 0 1 2 1 SMR 1.35 2.94 3.27 0 4 3 5 SMR 1.68 1.85 9.80 0 7 5 7 SMR 2.04 1.97 7.53 * cumulated to end of service 1 20.00 0 0.00 3 6.77 4 5.58 4 5.80 4 2.06 15 2.85 23 3.03 Cause of death Table 5 Estimates of exposure - response from case - referent analysis No. of cases Time from first 3 = % Increase in relative risk employment (y). (O.R.) per fib ml" year (95% Cl) Respiratory cancer 4 (ICD 160-163) 4 0 -9 10-19 15 >20 23 all 2.1 (0.0, 63) 0.4 (-0.1, 8.5) 1.0 (0.3, 9.7) 0.7 (0.1, 3.0) ' X*(l df) for Hq:3=0 3.08 1.23 7.04 7.49 Pneumoconiosis (ICD 515) 8 Mesothelioma (ICD various) 4 all all (:S20) ` 0.3 (0.0, 4.1) 0.2 (-0.2, 100+) 2.42 ' 0.10 00022 Figure T - Dust particles and fibres collected on membrane filter in the new wet mill. Transmission electron microscope view. (1 mm = 0.24 pm) 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET Figure 2 - Respiratory cancer SMRs 20 or more years from first employment and Cumulative exposure (f/ml.-` y.) SMR Constrained Unconstrained i . ... 500 1000 f/ml.-1 y. ~r 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET ! 00024 REFERENCES 1. McDonald JC, Sbastien P, Armstrong B (1985) Radiological survey of past and present vermiculite miners exposed to amphibole fibres in the tremolite series Brit J Indust V'edfin press) 2. Sbastien P, Armstrong B, Case B, McDonald JC (1985) Estimation of'amphibole exposure from asbestos body and macrophage counts in sputum: a survey in vermiculite mines Presented at .VI International Symposium on Inhaled Particles, ' Cambridge, Sept. 2-6, 1985 3. Sbastien P, Green F, Case B, Harley R, McDonald AD, McDonald JC (1985) Tremolite and chrysotile fibres in human lung. Presented at: VI Inter national Symposium on Inhaled Particles, Cambridge, Sept. 2-6, 1985 4. Ross M, Kuntze RA, Clifton RA (1984) A definition for asbestos In: Levadie, B. ed: Definitions for asbestos and other healthrelated silicates. STM, Philadelphia: 139-147 5. McDonald JC (1984) Mineral fibres and cancer Ann Acad Med Singapore 13(S): 345-352 6. Report of the Royal Commission on matters of health and safety arising from the use of asbestos in Dntario (1984), . Queen's Printer for Ontario, Toronto 7. Achesori ED, Gardner MJ (1983) Asbestos: the control limit for asbestos Health and Safety Commission, HMSO, London 8. Kleinfeld M, Messite j, Kooyama D (1967) Mortality experience in a group of asbestos workers Arch Environ Hlth _15: 177-180 9. Brown DP, Dement JM, Wagoner JK. (1979) Mortality patterns among miners and millers occupationally exposed to asbestiform talc In: Lemen R, Dement JM, eds,'Dust and disease, Pathotox, Park Forest South, 111: 317-324 10. McDonald AD, McDonald JC, Pooley FD (1986) Mineral content of lung in msothlial tumours in North America Ann Occup Hyg 26: 417-422 11. 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 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 2. 12. 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 13. Churg A, Wiggs B, Depaoli L, Kampe B, Stevens B (1984) ' Lung asbestos content in chrysotile workers with mesothelioma Amer R evR espir Dis 130: 1042-1045 14. 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 15. Rousseaux JM, Rouxhet PG, Vielvoye LA, Herbillon AJ (1973) The vermicuiization of trioctahedral. micas. The K Level and its correlation with chemical composition Clay Min 10: 1-16 16. Atkinson GR, Rose D, Thomas K, Jones D, Chatfield EJ, Going JE (1981) Collection, analysis and characterization of vermiculite samples for fibre content and asbestos contamination. US Environmental Protection Agency, Contract No.68-01-5915 17. US Department of Labor (1980) Asbestiform and/or fibrous minerals in mines, mills and quarries Mine Safety and Health Administration, '18. WaUort WH (1982) .The nature, hazards and assessment of occupational exposure to airborne asbestos dust: a review Ann Occup Hyg 25: 117-24? 19. Sbastien P, Gaudichet A, Billon-Galland MA, Janson X (1980) * Spectromtrie X par dispersion d'nergie en microscopie lectronique transmission: application la. caractrisation des fibres minrales J Microsc Spectrosc Electron 5: 83- 97 20. International Mineralogical Association (1978) Nomenclature of amphiboles Can Mineral 16: 501-520 21. Edwards GH, Lynch JR (1968) The method used by the US Public Health Service for enumeration of asbestos dust on membrane filters Ann Occup Hyg 11: 1-6 22. Corn M, Esmen NA (1979) Work place exposure zones for classification of employee exposures to physical and chemical agents Ann Ind Hyg Assoc J 40: 47-57 00026 / \` _________________ -- 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 23. Oldham PD (1965) On estimating the arithmetic means of lognormally-distributed populations ' Biometrics 213: 235-239 24. Monson R (1974) ' Analysis of relative survival and proportional mortality Computers and Biomedical Research 7: 325-332 25. Hanley J and Liddell FDK (1985) Fitting a relationship between exposure and SMRs J Occup Med (in press) 26. Thomas DC (1981) General relative risk models for survival time and matched case-control analysis Biometrics 37: 673-686 ` 27. Doll R, Peto j (1985) Effects on health of exposure to asbestos Health and Safety Commission, HMSO, London > 28. Liddell FDK, Thomas D, Gibbs GW, McDonald JC (1984) Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrysotile production in Quebec, 1926-75 Ann Acad Med Singapore, S: 340-344 -29. Oakes -D, McDonald JC (1982) Restricted cohort study designs Scand J Work Environ Hlth 8 S: 30-33 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00027 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 1. Abstract Chest radiographs taken by a standard technique were obtained from 173 current employees (164 males and 9 females) of a vermicuiite mine in Montana, from 80 of 110 past employees resident within 200 miles and from 47 men from the same area without known dust exposure. In 43 of the 80 and 24 of the 47, an earlier chest X-ray was retrieved from the hospital archives. All 367 films were assessed blind and inde pendently by three experienced readers using the 1LO 1980 classification. Median radiographic assessment scores were analysed in relation to esti mated cumulative exposure to the amphibole fibres which contaminate the vermicuiite. Logistic regression analyses showed independent effects of age, smoking and exposure on the prevalence of small opacities and of a*ge and probably of e tposure on pleural thickening. Overall, the data suggest that by retirement age, the increase in prevalence of small opacities ( & 1/0) lies between 5% and 10% per 100 f/ml years. This gradient may be somewhat steeper than for chrysotile miners and millers, but not much so. 00029 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 2. 2. Introduction The survey described in this paper is one of a series of studies undertaken to assess the health effects of work in a vermicuiite mine in Libby, Montana. Two complementary programs of research were initiated by NIOSH and ourselves, primarily because of contamination of the ore body with fibrous amphibole deposits in the tremolite series. A history and description of the mining and milling processes were given in our report on a cohort mortality study in this group of workers (1). These data showed substantial excess mortality compared to US white males from respiratory cancers (SMR = 2.45), non-malignant respiratory disease (SMR = 2.55) and malignant mesothelioma (Proportional mortality = 2.4%). The NIOSH mortality study of a more broadly defined cohort obtained similar results from independantly assembled data (2). Vermicuiite, a micaceous mineral which expands on heat treatment has many uses in construction industries, agriculture and packaging. The largest known vermicuiite deposit, at Libby, Montana, has been commercially mined since 1923. At first it was on a very small scale but, after 1939, when two companies merged, 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 incor porating rubber-tire loaders and trucks for both ore and waste removal. Waste is 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 of process improvements resulted in present mine personnel operating from within enclosed air-controlled cabs and a totally wet beneficiation process. Vermi cuiite concentrate is graded into five size fractions before shipment to expansion plants in various parts of the United States. 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00030 3. Fibrous tremolite has little commercial value and only one or two very small mines in Northern Italy produce it. On the other hand it is a fairly common contaminant in various exploited minerals, notably some talc deposits of New York State, and in the Qubec chrysotile mines where it is present in trace amounts. There has been no previously published radio logical survey of tremolite miners as such, but several studies of talc miners and millers exposed to varying levels of mineral fibre and silica (3). Pleural thickening was frequently found in these workers but parenchymal opacities much less so. These observations are not easily interpreted in terms of tremolite fibre, because of the other components in the airborne dust. 3. Material and methods 3.1 Study groups - Chest radiographs were obtained from persons in three groups. The first comprised all 164 men and 9 women employed by the company on July 1, 1983. The second, was selected from 110 past male employees, .resident within 200 miles of the mine. This information was known as all. had been traced as surviving members in the mortality cohort, the criteria for inclusion of which were employment of at least one year and date of hire before 1 January 1963. Eighty of the 110 thus identified accepted the company's invitation to come to the hospital in Libby for a chest X-ray. The third group comprised 47 men without known dust exposure who attended the hospital during the same period for a 'routine' chest X- ray, mostly in connection with other local employment. The latter group was not selected or matched in any way with the mine workers and was intended only to control the reading process. All 291 men (and 9 women) in the three groups were X-rayed by a standard technique, based on that outlined in Appendix A of the 1980 1LO Guidelines (4). In 43 of the 80 ex-employees and in 24 of the 47 unexposed subjects, an earlier chest X- ray was located in the hospital film archives. The earlier films for the ex-employees had usually been taken shortly before leaving the company and by a generally less satisfactory radiological technique. In total, 367 films were tbi* >led for classification. 00031 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 4. 3.2 Reading procedures - The films, with identity obliterated, were renumbered in random order and classified independently by three experienced readers. The ILO 1980 International Classification and standard sets of films were used. The readers were told only that the films were mainly from mineworkers with varying exposure to mixed dusts and that about 20% of the series were unexposed subjects. Preliminary tabulations after the readings were completed showed that, overall, 567o of the recent films were considered of good quality, 36% fair, 7% poor and .0.4% unreadable. The corresponding ratings for the older films were 22%, 53%, 23% and 2%. Although the readers were very experienced and had worked together often, inter-observer variation remained. Agreement between all three readers on the presence or absence of changes was acheived in about 90% of readings for pleural calcification, costo-phrenic angle obliteration and pleural thickening on the diaphragm. The rate fell to about 80% for .small parenchymal opacities and for pleural plaques or diffuse thickening. 3.2 Exposure estimates - Work histories were used to obtain the dates and duration of work in various locations. The mean airborne fibre concen trations for each location - operation, year by year, were estimated from all available midget impinger and membrane filter measurements after a detailed site visit and review by one of us (PS). The methods of esti mation and results are described fully in the mortality paper (1). 3.4 Statistical analysis - Radiographic readings from the three readers were combined as a median score. Two methods were used to investigate relationships between X-ray changes and exposure to fibrous dust. Firstly, the prevalence of abnormalities was tabulated in five cumulative exposure groups, after stiatification in three age groups (20-39, 40-59, 60 +) to reduce confounding. Age-standardised prevalence rates were then computed for each exposure group, the combined population being taken as standard. Secondly, logistic regression analyses for selected abnormalities were carried out in which age, smoking and cumulative exposure were entered into the regression equation. Age was considered as a continuous variable, and 00032 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 5. smoking in three groups:- never smoked, ex-smoker and current smokers. The logistic regression, analysis and the fitting of linear exposure-response lines to the grouped prevalences were carried out using the GLIM computer package(5). 4. Results The prevalence of the main radiographic changes in the current male employees and the sample of past employees, based on their most recent films, is presented in Table 1. The overlap between the two groups is confined to men aged 40 and over. Even in these older men, the rates for both parenchymal and pleural changes differ considerably but, perhaps not more than might be explained by differences in mean levels of cumulative exposure. A steep age gradient in both groups is also evident, probably attributable in part to exposure. Of the 47 unexposed subjects, 32 were aged 40 or more; small opacities were read in 1, pleural thickening on the chest wall in 4 (8.5%) and pleural calcification in 2 (2.7%). Age standardised prevalences of small opacities and pleural thickening by cumulative exposure are given in Table 2. Because of small numbers and, in particular, since very few young men had achieved high cumulative exposures, these standardised rates are subject to rather large standard errors in the higher exposure groups. Notwithstanding these problems, the trend of increasing prevalence of small opacities with increasing exposure is unlikely to be due to p chance, (X (ldf) = 5.4, p = 0.02). The corresponding trend for prevalence of 2 pleural thickening of the chest wali is less strong (X (ldf) = 2.6, p = 0.10). Prevalence of abnormalities by cumulative exposure for men aged 60 and over is given in Table 3. Here too there is an association of . small 2 opacities with exposure (X (ldf) = 6.4,p -0.01) and a weaker one for pleural change (X2(ldf) = 0.9, p >0.20). Results of the logistic regression analyses of abnormalities are given in Table 4. These show the independent effects of each of the three factors examined (cumulative exposure, age, and smoking), after allowing for the other two. Clear effects of cumulative exposure and age on the prevalence of small opacities are apparent and there is also some indication of a smoking 00033 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 6. effect (p = 0.02). ' The prevalence of pleural thickening on the chest wall is affected by age and more weakly by cumulative exposure (p =0.02). There is no consistent evidence of a smoking effect. The data are insufficient to deter mine whether there are interactions between the factors. The estimated exposure-response, relationships for small opacities are graphed in Figure 1, together with prevalences by cumulative exposure. The graph shows the linear relationships computed from Table 2 and 3, and that predicted from the logistic regression equation for age 65. The latter includes two curves, one for current smokers and one for non-smokers. The curve for ex-smokers would be intermediate. For all these relationships, standard errors of slopes and intercepts are large. Among the 43 ex-employees for whom an earlier X-ray had been obtained, small opacities ( a 1/0) were read in 18 (42%) of the 1983 films and 9 (21%) of the films taken on average 8.9 years earlier. This difference derived from 10 men whose readings had deteriorated and 2 whose readings had improved. In the 24. pairs from unexposed men, on average 7-8 years apart, no abnormality was read in the earlier film and one only in the later film. Since there was virtually no change in the cumulative exposure of the 43 ex-employees between their two X-rays, the substantial increase in prevalence was presumably due in part to aging and in part to differences in radiographic technique. 5. Discussion The usual criticism leveled at cross-sectional morbidity studies in working groups is that selection may have removed a disproportionate number of employees who had suffered the ill-effects of occupational exposure. It would of course be equally wrong to study only ex-employees. We tried in this survey to acheive a balance by including both present and past employees and analysing their joint exper ience. In addition to the logistic regression analysis presented in Table 4, another 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 7. analysis was made in which a fourth variable for ex or current employ ment was included. This showed that, having allowed for the other three factors, rates of change were higher in past than present employees but, statistically, not significantly so. The coefficient for the relationship to exposure was, in fact, the same whether or not the . fourth variable was included . We believe, therefore, that it is reasonable to base our estimate of exposure-response on the experience of the combined sample. Even so, the relationships illustrated in Figure 1 entail very great uncertainty, for which there are several reasons. Firstly, the exposure estimates, especially for the important period before about 1972, were approximate. Secondly, radiographic techniques and X-ray readings are major sources of variation. Thirdly, age, smoking and probably other environmental factors all contribute to radiographic change. Finally, the study sample was quite small. In the absence of other information, our data provide the only indication of risk in relation to exposure. Of the four lines shown in Figure 1, the two based on logistic regression and the one for men aged 60 or more are roughly parallel, and probably more valid than that based on age-standardization. These three lines suggest that by retirement age the increase in prevalence of small parenchymal opacities ( 1/10) lies between 5% and 10% per 100 f/ml years. At present exposure levels in the Libby operation, reported by the company to average 0.1 f/mi, no excess of radio logical change should be detectable after a working life of 40 years. ` The imprecision associated with radiological technique and reading error would be far greater than the expected level of risk. There are few other data sets against which these findings can be compared. Our original studies of Qubec chrysotile miners (6) gave a slope of about 0.6% per 100 fibre years and a later analysis (7), confined to men aged 60-69 with an average gross service of 42.3 years, gave a lower estimate (0.2%). Both these estimates were based on men still at work and it was concluded that the true gradients were probably steeper. A more recent study of the Qubec workers (8) was based on current and past employees, used X-rays taken with a similar technique to that at Libby and one of the three readers took part in both studies. That study gave a slope of 4% per 100 fibre years, about half that in the present survey. 00035 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 8. The radiographic study by NiOSH (2) was based on the most recent chest X-rays (188 in all) available in the local hospital for men employed 5 or more years and at some time since 1974. These men were all current employees at the time of the X-ray, were somewhat younger than those in our sample but had been employed nearly 4 years longer and at a slightly higher average level of exposure. Despite this, and the fact, that one of the readers was common to both studies, the prevalence rates of both parenchymal and pleural changes were substantially higher in our study than theirs. The slope of the logistic regression line for small opacities ( 1/0) and cumulative exposure was also some what steeper in our data. We believe that these differences were due to better film quality and perhaps to the inclusion of ex-employees in our survey. This underlines the problems and imprecision of radiographic estimates of exposureresponse in dust-exposed workers. Acknowledgement This research was supported by a grant to McGill University from W.R. Grace and Co.' The chest X-rays were taken at St. John's Lutheran Hospital, Libby, Montana under the supervision of Dr Tyler Gill and read by Dr John Gilson, Dr Robert Jones and Dr Geoffrey Sheers. The active participation of past and present employees and the Company is gratefully acknowledged. 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 00036 References 1. McDonald JC, McDonald AD, Armstrong B, Sbastien P. (1985). Cohort study o f. mortality of vermicuiite miners exposed to tremolit. Brit J Industr Med (in press). 2. Amandus HE, Wheeler R ( 1985 ). Mortality of vermicuiite miners exposed to tremolite asbestos ( to be published ). 3. Dement JM, Zumwalde RD, Gamble JF, Felluer W, DeMeo MJ, Brouwn DP, Wagoner JK (1980). Occupational exposure to talc containing asbestos. NIOSH Technical Report, US Government Printing Office, Washington DC. 4. International Labour Office (1980). Guidelines for the use of the ILO inter national classification of radiographs of pneumoconioses. Occupational Safety and Health Series 22(Rev 80). ILO, Geneva. 5. Baker RJ, Nelder JA (1978). The GL1M System; Release 3, Numerical Algorithme Group, Oxford. . 6. RoSsiter CE, Bristol LJ, Cartier P.H, Gilson JC, Grainger TR, Sluis-Cremer GK, McDonald JC (1972). Radiographie changes in chrysotile mine and mill workers of Quebec. Arch. Environ Health 24: 388-400 7. Liddell FDK, Gibbs GW, McDonald JC (1982). Radiological changes and fibre exposure in chrysotile workers aged 60-69 years at Thetford Mines. Ann Occup Hyg 26: 889-898 8. McDonald JC, Gibbs GW, Oakes D (1984). Radiographic response to cumulative chrysotile fibre exposure in production workers 8-29 years after first employment. Presented at XXI International Congress on Occupational Health, Dublin. 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET ro. Table 1 Percentage of radiographic changes by age Current employees. Past employees Small Pleural Pleural n opacities ; thickening calcification i 1/0 (chest wall) f m l 1 y* Small opacities z 1/0 Pleural Pleural thickening calcifici (chest wall) 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET 2.5 7.5 13.0 20.3 26.7 40.0 9.1 15.9 1.3 6.0 5.8 30 160.2 33.3 6.7 49 96.1 40.8 3.7 80 118.9 37.5 40.0 16. 61.2 36. 52.5 28. 1 1; Table 2 Age standardised prevalence of abnormalities by cumulative exposure //AS:V I- :'' "4 ^ Cumulative ecposure ( fib m f 1 y) . Croup Mean <10 4.1 10, < 20 17.5 20, < 100 53.9 100, < 200 144.4 200 495.8 Total 65.9 Number in group 92 64 53 16 19 244 Small opacities > 1/0 Number Preval ence%* 7 10.6 12 . 18.4 10 15.4 8 31.3 8 27.9 45 18.4 Pleural thickening of chest wall Number Prevalence0^ 15 23.3 14 21.7 22 38.7 . 6 22.2 11 38.5 68 27.9 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET Directly age standardised, total study group taken as standard 12 Table 3 Prevalence of abnormalities in men aged 60 or more by cumulative exposure Cumulative exposure (fib ml-1 y) Group Mean < 10 6.5 10, <20 19.0 20, <100 56.7 I00,<200 153.4 S200 463.4 Total 97.9 Number in group 15 17 16 8 8 64 Small opacities . s 1/0 Number Prevalence^ 2 13.3 6 35.3 6 37.5 6 75.0 4 50.V 24 37.5 Pleural thickening of chest wall Number Prevalence% 7 46.7 9 52.9 10 62.5 5 62.5 5 62.5 36 56.3 Table 4 Logistic regression analysis of exposure-response relationships 13. ' . Test for: In the presence of: Cumulative , exposure Smoking Age . Age, smoking Age, cumulative exposure Cumulative exposure, smoking Small opacities 1/0 X2 { df ) P 10.9(1) p<0.001 8.2(2) p<0.025 27.2(1) pCO.OOl Pleural thickening of chest ' X2 ( df ) P 5.9(1) . p<0.025 4.6(2) p=0.10 28.1(1) p <0.001 Estimated coefficients Small opacities: , Log ( P ) 1-P - 7.27 + 0.0035 ( cum. exp. ) + 0.084 ( age ) + {0.82 if ex-smoker { 1.72 if current smoker Pleural thickening: Log ( P ) = - 5.62 + 0.0024 .( cum. exp. ) + 0.088 { age 1-P + {-0.41 if ex-smoker { 0.42 if current smoker 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET CERTIFICATE OF AUTHENTICITY THIS IS TO CERTIFY that the microimages appearing on this microfiche are accurate and complete reproductions of the records of U.S. Environmental Protection Agency documents as delivered in the regular course of business for microfilming. Data produced. / (Month) / ? _____ 2 Z (Day) (Year) Place Syracuse (City) New York (State) Camera Operator aAMTEK conp 0 2 / 1 4 / 1 9 9 6 EPA TSCA DOCKET