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DRAFT for discussion 1 . Proposal for a Longitudinal Study of the Respiratory Health of Talc Workers L. Whitehead T. Ashikaga I. Proposed Study A longitudinal study of pulmonary function and respiratory symptomatology in employees of Windsor Minerals is proposed The primary objective of this study is to further delineate the relationship between occupational exposure to asbestiform talc and its ore and respiratory health The specific aims are 1 To determine if changes in pulmonary function and reported respiratory symptoms greater than those observed in Vermont comparison groups without dust exposures can be detected in workers with occupational exposures to asbestiform talc | COPY : 2 To determine if rate of change of pulmonary function and are related to environmental levels respiratory symptoms of respirable dust in the talc mines and mill A secondary objective is to assess the feasibility of one or more followup techniques to determine whether selective removal from the work force occurs due to respiratory illness pe aa II Rationale Talc workers in Vermont are in an unusual setting talc in Vermont is claimed to be essentially free of either silica or asbestos both of which are often found in conjunction with talc deposits Hence an opportunity exists to study the effects of talc in the absence of hazardous contaminants Previous studies Rubino et.al. 1976 Kleinfeld et.al. 1964 1967 1974 have been made on workers poet eee 0096952 JNJ 000037268 Page 2 exposed to talc containing such contaminants In 1972 Sylwester and Green 1976 surveyed the talc workers in one talc mine and mill in Vermont as part of the Pulmonary SCOR Specialized Center of Research at the University of Vermont Excess reported symptoms were found but no significant pulmonary function decrement due to dust exposures was observed Two other studies have recently been carried out on talc workers in Harvard University has completed a year prospective study of pulmonary function in Vermont talc workers but results are not yet available A principle goal of that project was to obtain evidence for a proposed talc occupational standard initially proposed in the report of a study of rubber workers exposed to talc Fine et.al. 1975 The second project concerning Vermont tale workers has been conducted by NIOSH in cooperation with VOSHA on the mortality experience of talc workers in the state Again no results have been published but a technical summary appeared in the Wall Street Journal of November 2 1976 in which an excess of mortality is reported from cancerous respiratory disease and a lesser excess from lung cancer The study and the methods used have not yet been published and are not available for review and evaluation as of February 1977 The effects if any of occupational exposure to asbestiform talc are therefore not yet clearly defined Also the possible inter- actions between talc exposure and variables such as age smoking history and respiratory status prior to occupational exposure to talc have not been fully evaluated This study is proposed as a logical 0096953 JNJ 000037269 Page 3 extension of the SCOR and Harvard surveys The longitudinal design will provide an opportunity to relate changes in respiratory health over time if any to selected employee characteristics and environmental conditions If deleterious effects on respiratory health are detected appropriate preventive measures can be developed III Pulmonary Function Model The basic pulmonary function decrement model that is hypothesized herein is illustrated in Figure 1. The average population pulmonary function trend is assumed linear at least over the relatively short period of this study with components due to age smoking history sex etc. This however is merely the trend observed and it is hypothesized that the actual functions are cyclic with average population pulmonary function in winter due to increased respiratory infection and symptoms and with highest average function in summer due to lower prevalence of infection McKerrow and Rossiter 1968 reported an annual cycle in FEV 0.75 in 28 pneumoconiotic working miners of 44 mi amplitide and a cycle of 10 ml in laboratory workers The miners average cycle was at a minimum in early February and a maximum in early August when fit by a sine curve but there also was wide variation in peak times in individuals The cycle could not be explained by weather variable cycles and they suggest that it may be an intrinsic biologic rhythm A. second hypothesis is that the variance of lung function es- timates will be greatest in winter and least in summer due to larger between and within individuals variation from both increased preva- 0096954 JNJ 000037270 SLNIOd [ PUNOJD i933 x VARINCE 2| 86) UO!{DIUA TREND JONVIA X SEASONAL EFECT puasy | YpIM O86! japowuoljoun; Xx 1 O3ZISHLdA ONS3Yl x 6261 uoNsUNy Ainuowjnd j Bun) SURVEY SURVEY 6261 1982 | D YV3NIT Hypothesized linear average +} seasonal variation J&J-0096955 JNJ 000037271 Page 4 lence and varying degrees of severity of acute upper respiratory infections and exacerbation of chronic respiratory problems Sargeant and Tromp 1964 report increased bronchitis colds and influenza with possibly increased variation in pulmonary function in the period December to February though they report a slightly offset | cycle for asthma peaking in late autumn and relatively low in mid- _ winter McKerrow and Rossiter 1968 did not present variation by time of year While Figure 1 illustrates equal excursions around the trend from year to year this may not be assumed such as influenza epidemics could severely bias pulmonary function surveys at a point in time but do not occur in all winters Several guidelines are suggested by this model ) term pulmonary function trend surveys will encounter less noise variance ' due to superimposed temporary conditions if made in summer 2 surveys to be compared with other surveys should be taken in the same seasons 3 surveys to detect absolute values of pulmonary function rather than trends such as annual decrement should either a average winter and summer surveys or b occur in fall or spring to approximate better the average value of the function of interest The statements discussed above will now be stated as hypo- theses 1. Average summer lung function in the population will be higher than in winter 2 Winter surveys will exhibit higher variance than summer surveys 0096956 JNJ 000037272 Page 5 To investigate these hypotheses as well as detect basic pulmonary function decrement rates in Windsor Mineral talc workers the following study design is proposed refer also to Figure ) not less than three sets of surveys of the entire cooperating Windsor Minerals employee population. will be made in both winter and summer at year intervals with a minimum length of study of 4 years resulting Comparisons will be made between mean winter pulmonary function and reported symptoms and mean summer values to test hypothesis 1 further the differences in variances encountered in winter and summer will be compared and tested for difference IV Possible Annual Cycle Survey After the initial pair of surveys scheduled for summer of 1977 and winter of 1977-78 a special annual cycle study will be explored for feasibility Accompanying budgets do not provide for conduct of the special study Such a budget would be negotiated separately should the special study be undertaken If it is found to be feasible to detect monthly trends as estimated from the initial winter and summer survey results with a sample size that can be reasonably obtained a subsample stratified by dust exposure of the Windsor Minerals employee population will be surveyed monthly for one year to estimate the magnitude of the annual cycle This special monthly survey series is not critical to the basic questions of detecting pulmonary function decrement in talc workers and comparison groups but it would contribute to pulmonary function studies in general 0096957 JNJ 000037273 Page 6 would be conducted to completely Not less than 14 monthly samples with one survey prior to this to minimize j bracket one month period | effect in the main monthly surveys themthe training or familiarity selves v Pulmonary Function Comparison Values Published predictive equations for expected or normal lung values for observed lung function will be used to establish comparison function of Windsor workers Equations will be used both from studies elsewhere and for Vermont workers without dust exposures SCOR data factor in the proposed longitudinal survey is the A complicating institution of a spirometric hiring standard at Windsor proposed Minerals This will result in a continually increasing proportion of who were selected for good lung function workers at Windsor Minerals to stratify Windsor workers into those selected It will be necessary by this standard and those not so selected Predictive equations for expected lung function for the workers hired under the spirometric standard with initially high values those will be developed from the SCOR data set Several hundred workers were surveyed in 1972 and 1976 for pulmonary function These can be stratified into groups meeting and failing to meet the Windsor hiring criteria on the 1972 survey Then for those meeting the Windsor models will be developed using the 1976 followup criteria predictive data This will provide predictive models for a population selected for initially high lung function reasonably comparable to the Windsor workers hired after meeting a similar spirometric standard 0096958 JNJ 000037274 Page 7 The SCOR data offer a second form of comparison This study proposes surveys at year intervals and specifically will allow a year followup survey on all workers still at Windsor The SCOR surveys also document a year followup on many Vermont workers These workers will be matched to Windsor workers smoking status and other relevant variables if possible and year decrements will be compared VI Specific Approach A. Employees of Windsor Minerals will be surveyed twice per year summer and winter every other year for five years a total of 3 pairs of seasonal surveys Each survey will include administration of a questionnaire and spirometry In addition optional studies of a subsample may be carried out as discussed above B. Environmental sampling for respirable dust will be conducted in the mine and mill during the same year period characterizing exposure in all types of work areas during each year of the study This will serve principally as a validation for the samples regularly collected by Windsor Minerals C. Terminating employees of Windsor Minerals will be invited to continue participation in the study for a minimum of one year after termination Any who terminate during the final year of the project will be asked to participate to conclusion of the study period 0096959 JNJ 000037275 Page 8 VII Methods A. Spirometry Spirometric tests will include FVC FEV and PEFR Measure- ments will be made with a Hewlett 47401 Lung Function Analyzer with graphic and numerical output or similar equipment Questionnaire A modification of the SCOR Sylwester and Green 1976 questionnaire will be used Modifications will include the addition of questions on employment history brand of cigarette smoked weight and physical activity Sr Job Positions All changes in employees job positions and reasons for changes will be recorded by Windsor Minerals personnel at the time they occur on a form to be developed Medical Records Information pertinent to the duration and cause of absen- teeism for medical reasons will be abstracted from Windsor Minerals medical records after obtaining employee permission In addition results of employment physical exams and spirometric tests will be abstracted Environmental Sampling Respirable mass samples of dust will be obtained by fullshift personal samplers for all work area types specifically 0096960 JNJ 000037276 Page 9 including mill crusher and bagging areas processing areas and mining operations These data will be used to characterize the current dust exposures in the industry Such comprehensive sampling will be carried out simultaneously with each industry survey or six times during the project in order to characterize both winter and summer exposures which may be different due to differing ventila- tion etc. Further Windsor Minerals will continue its own monitoring program of continual spotchecks of respirable mass dust exposures Compatibility between methods and results of this project and Windsor Minerals methods and results will be investigated MESA data and other previously collected data will be obtained and these will allow an adequate characterization of dust exposures for the past three years Exposures prior to that date will be estimated eiahs based on known process characteristics and modifications if any workers are present with such long exposures Samples collected will be analyzed gravimetrically and selected samples will be analyzed for free silica and asbestiform fibers In addition Windsor Minerals will provide analysis data on ore samples and product samples that are routinely analyzed by their consultants 0096961 JNJ 000037277 REFERENCES Fine L.J. et.al. 1975 Studies of Respiratory Morbidity in Rubber Workers IV Respiratory Morbidity in Talc Workers Manuscript Kresge Center for Environmental Health Harvard School of Public Health Boston Massachusetts Kleinfeld M. et.al. 1964 Env Health 559-566 Lung Function in Talc Workers Arch Kleinfeld M. et.al. 1967 Mortality among Talc Miners in New York State Arch Env Health 663-667 and Millers Kleinfeld M. J. Messite among Talc Workers A 345-349 and M.H. Followup Zaki 1974 Mortality Experiences Study J. Occupa Med 16 McKerrow C.B. and C.E. Rossiter 1968 An Annual Ventilatory Capacitoyf Men with Pneumoconioses Subjects Thorax 340-349 Cycle in the and of Normal Rubino G.F. et.al. 1976 Mortality Study of Talc Miners Millers J. Occupa Med 186-193 and Sargent F. and S.W. Tromp Technical Note No. 65 Switzerland 113 pp eds 1964 A Survey of Human Biometerology World Meterological Organization Geneva . D.L. and G.M. Green 1976 Respiratory Assessment of Sylwester Windsor Talc Workers Depts of Epidemiology & Environmental Health and Medicine University of Vermont Burlington Vermont 0096962 JNJ 000037278