Document n94EMejbrQVBy14YrN6Ky8XJa

SZPCRT ;:c. TA/*Z/b OOC 512.2 J 67?.7**3 AK EPIUEtfICLCCTCAL STUDY OF THE LPNG FUNCTION CF JCSKZBS AT A FACTORY MANG FAC7TT3IKG FOLYVIHYLCITLOaiDE by HH Lloyd S Gauld L Copland CA Soutar JANUARY 1952 ucc 027782 INSTITUTE OF OCCUPATIONAL MEDICINE AN EPIDEMIOLOGICAL STUDY OF THE LUNG FUNCTION OF WORKERS AT A FACTORY MANUFACTURING POLYVINYLCHLORIDE by HH Lloyd, 3 Gould, L Copland, CA Soutar Madical Branch Institute of Occupational Madlclaa, Roxburgh Placa, EDINBURGH EE8 9SU. (Tal. 031 667 513D JANUARY 1982 ucc 027783 (ii) CONTENTS ABSTRACT ............................................................................. 1. INTRODUCTION .............................................................. 1.1 Respiratory effects of VCM and PVC . . 1.1.1 Animal studies ...... 1.1.2 Clinical studies ............................... 1.1.3 Epidemiological studies ... 1.2 The present study ....... 1.2.1 The PVC factory ..... 1.2.2 The foundry ....................................... 2. METHODS..................................................................... 2.1 Selection of the survey population . . 2.2 The medical survey ...... 2.3 Methods of analysis ...... 2.3.1 Classification of smoking histories 2.3.2 Analysis of data from total survey population ...... 2.3*3 Selection of cases and controls 2.3.4 Case-control study ..... 3. RESULTS ............................................................................. 3*1 Description of total survey population 3.2 Analysis of lung function data from total Survey population ....... 3.2.1 Calculation of predicted values and standardised residuals 3.2.2 Distribution of standardised residual values of T-co and FEV1 for total survey population ..... 3.2.3 Selection of cases and controls . 3*3 General features of cases, controls and the total survey population ..... 3.3.1 Age, height and weigit ... 3.3*2 Employment status and smoking habit 3.3.3 Lung function ...... Page No. (iv) 1 1 2 2 3 3 4 5 6 6 6 7 7 7 8 8 10 10 10 10 10 10 11 11 11 11 ucc 027784 (iii) Page No. 3.4 Clinical description of Ttco cases and FEVt eases ......... 3.3 Case-control study ........ 3.5.1 Occupational histories of cases and controls ........ 3*5.2 Smoking habits of cases and controls . 12 12 12 14 4. DISCUSSION..................................................................................... 16 5. CONCLUSIONS AND RECOMMENDATIONS............................................... 19 AC KM O'WLEDGEMENTS REFERENCES TABLES FIGURES APPENDICES ucc J 027785 Report No. TH/82/4 (iv) INSTITUTE OF OCCUPATIONAL MEDICINE AN EPIDEKIOLCGICAL STUDY OF THE LONG FUNCTION" OF WORKERS AT A FACTORY MANUFACTURING POLYVINYLCHLORIDE by MH Lloyd, S Gauld, L Copland, CA Soutar ABSTRACT have conducted an epidemiological study to investigate a report that some men working in a factory manufacturing polyvinylchloride (PVC) had abnormally low values of one lung function'test, namely the sirgle breath transfer factor for carbon monoxide (Toco). We studied 265 present and past employees of the PVC factory, and 219 men from the workforce of a nearby foundry. The foundrymen were included to increase the number of men with little or no exposure to possible respiratory hazards at the PVC factory. Each man's Toco was measured, and smoking history and detailed occupational history obtained. More detailed lung function tests were carried out on the PVC workers only (forced expiratory flow-volume curves). The study consisted of two parts; measurement of the Tuoo of current and past employees at the factory and current foundry employees and examination of the distribution of residuals after allowing for age, height, weight and smoking habit, to search for evidence of an excess of men with low values of Tuco; and a case-control study. In this, men with the lowest Tuco after allowing for age, height, weight and smoking habit were selected as cases, and their occupat ional history compared with that of two groups of controls; one group selected from those with near average gas transfer values, and another group from those with the highest values. The Tlco results among this combined population conformed to a Normal distribution after allowing for age, height, weight and smoking habit, and did not suggest that a substantial number of men had clinically important impairment of their Tt-co. The 31 men selected as 'cases' included 15 men whose Tuco was abnormally low (less than 7 of published predicted values), of whom nTrU*' we re PVC workers were foundrymen. Among the 19 cases working at the PVC factory the pattern of lung function abnormality suggested that the low Tuco was (v) accompanied by evidence of airflow obstruction in 11 men, suggesting the presence of emphysema, but was an isolated functional abnormality in the other eight, possibly suggesting the presence of pulmonary fibrosis or abnormalities of lung perfusion. PVC workers ware slightly over-represented among the cases, although this difference could easily have arisen by chance. Men who had worked on jobs at the PVC factory which were close to the pressure vessels where exposure to vinyl chloride monomer was most likely to have occurred in the past, were also slightly over-represented among the cases, and this difference approached statistical significance at conventional levels. There was, furthermore, a statistically significant association between low Tuco and a history of having worked at the PVC factory before 1975- This date is important because it was at this time that exposure of the workforce to vinyl chloride monomer was drastically reduced, in tho light of information about some of the potential hazards of this gas. The cases included slightly more smokers than the controls, and those cases who smoked, smoked slightly more Heavily than controls* The relative importance of these and other factors in causing the lung functional abnormalities is not clear, but these findings give some support to the hypothesis that work in the PVC factory before 1975 involved exposure to a substance that caused impairment of lung function in a small number of men. There was no evidence of a relationship between low TLco values and current working conditions at the PVC factory or with past or present conditions at the foundry. The results suggest that more detailed studies of the relation ships with vinyl chloride monomer, polyvinylchloride, smoking habit and other causative factors would be desirable, together with a clinical assessment of the lung damage in selected men. UCC 027787 1. INTRODUCTION The health of workers employed in the manufacture of polyvinylchloride (PVC) has been a cause of concern during recant years. Some adversa effects of exposure to vir.7l chloride monomer (VCM) are well recognized, but lung disease in men has net been shown to be related to exposure to VCM. Exposure to airborne PVC dust, however, has been shown to cause slight impairment of lung function and slight chest radiographic abnormalities. Vinvl chloride is the basic raw material used in the production of PVC. Although the manufacturing process was first developed in 1923 in the USA it was not until 50 years later that evidence of the toxic effects of vinyl chloride exposure began to accumulate. CCICTU?. (19rS)- vras the first to describe acro-osteolysis in reactor cleaners in Belgium and in the following year SCCIU (1967) described Raynaud's phenomenon among workers in a PVC factory. Changes in the skin and internal organs were subsequently recognised nd in 197** the tarm 'vinyl chloride disease' was used to describe the syndrome which Las cany features in common with scleroderma (VSLTMA7* al., 1975). The hepatic effects of exoosuro to VCM have aroused tho most interest and include sen-malignant changes. It was the discovery of the association between vinyl chloride exposure and angiosarcoma of the liver (CREECH and JOHNSON, 197*0 which caused the greatest concern and affirmed the need for stricter control of exposure levels. In 1975 regulations were introduced which established a ceiling exposure value of 50 parts per mill'ies (ppm) and an eight-hour time weignted average (TVA) of 10 ppm. In 1?30 the permitted maximum exposure was reduced to an annual average of 3 ppm. 1.1 Resniratorv effects of VCM and PVC The work described in this report was confined to a study of the lung function of workers in a factory producing PVC where men were exposed potentially to VCM, PVC and the other compounds used in the manufacturing process. Previous studies involving the use of animals, observation on patients and epidemiological surveys, have provided information on the potential respiratory effects of these compounds. ucc 027788 2 1.1.1 Animal studies The toxicity of both VC and PVC has been investigated in animal experiments. P30DAN et_ al. (1975) exposed guinea pigs to 1C0S vinyl chloride concentration for two hours daily for periods of up to three months. At autopsy the lungs of all exposed animals showed the presence of fibrosis which was most severe in the animals which had had tha longest exposure time. AGA5WAL et al. (1978) Studied the effect of intratracheal injections of PVC dust in rats and found that inflammatory changes were induced in the terminal and respiratory alveoli and that granulomatous lesions associated with multinucleated giant cells developed. Similar giant cells and histiocytes were identified in the alveoli cf the lungs of small mammals which were kept in the bagging area of a PVC factory (FBONGIA at al.. 197*0. 1.1.2 Clinical studies There have been isolated case reports of pulmonary disease in workers employed in factories manufacturing PVC. ABNAITD et al. (1373) studied a 53-year-old man who had worked for 23 years in the bagging plant of a PVC factory. Eis chest X-ray showed micronoduler shadowing and lung biopsy revealad large numbers of macrophages containing particulate material and moderate diffuse fibrosis and a few alveolar granulomata. However, his symptoms were few and apart from a slight reduction in. vital capacity, his lung function tests including his transfer factor for carbon monoxide were normal. His disease was probably related to PVC dust rather than VCM. DA3KE (1976) Investigated' 1^ men who Bad been employed in a PVC manufacturing plant exposed to VCH and all of whom complained of breathlessness. He found that their chest radiographs were normal. In six of these men transfer factor for carbon monoxide is reported am being impaired but no measurements or details of other lung function tests are given. Lung biopsy from one of the men showed focal alveolar wall thickening and macrophages present in alveolar spaces. LANGE et al. (1973) described some eases of VC workers with impairment of transfer factor for carbon monoxide, but the relationship with occupation was nob clear. -. ucc 027789 3 1.1.3 Epidemiological studies Studies of pulmonary function of workers employed in PVC manufacturing plants have produced conflicting results, and it has not always been possible to separate the effects of FVC dust from potential effects of VCM. A high prevalence of abnormal lung function, mainly obstructive in type, was found by MILLER et al. 0975) and LILIS et al. (1975; 1976) among workers in two PVC manufacturing plants in the United States of America but smoking was not taken into account in the analysis. Smoking effects were allowed for in the study by GAMBLE et al. (1976) which compared the lung function of workers in a PVC plant with that of rubber workers and chemical workers exposed to VCM: no significant differences were found in the lung function of these three groups but no measured personal exposures were available. V5RTKIN et al. (1970) studied 96 PVC workers in the USSR and found a high prevalence of chest radiograph abnormalities but the majority of the workers had normal lung function tests. CHIVERS et al. (1980) similarly found no apparent impairment of lung function among 509 employees in a PVC factory of whom 10^ were exposed to PVC dust only, 112 to non-chlorinated solvents only and the remaining 295 were exposed to a mixt-tre of both. Ho difference between the three groups was identified and the observed impairment of lung function in some men was related entirely to the effects of smoking. However, measured personal exposures were not available for these men. A study of 818 men currently and previously employed at a PVC manufacturing plant (S0UTA5 et al., 1980) in which estimates of personal exposure to PVC dust were based on detailed occupational histories and current measurements of dust levels in the factory showed a statistically significant reduction in teats of lung function among man with the highest FVC dust exposure, and some of these men had small rounded opacities on their chest radiographs. The men with these radiological changes had significantly lower mean lung function test values than men whose films were considered to be normal. No relationship was found between exposure to PVC dust and impaired transfer factor for carbon monoxide. 1.2 The present study The present study was requested by Vinatex Ltd., and was carried out with the full agreement of management and workforce, and arose from their concern about some employees whose lung function, particularly the ucc 027790 4 transfer factor for carbon monoxide, appeared to be abnormal- The transfer factor for carbon monoxide measures the ability of the lung to exchange gases between the inspired air and the blood. The study was designed to describe the distributions of various measures of lung function, including the transfer factor, in current and former employees at the FVC factory and to identify men with low lung function values. These men would be regarded as 'cases' and would be compared with two groups of controls, in order to examine possible associations between abnormally low lung function values and personal, occupational and environmental factors* The total survey population included the workforce of two factories; one was the ?VC factory of interest and the other was a large iron foundry situated a few hundred yards away. 1.2.1 The P'/C factory The plant had been in operation since 1969 and for most of that time had produced suspension polymer. For a period of three years (1971 - 197*0 emulsion polymer, which has a smaller particT.e size than suspension pclycer, had been manufactured in one of the two reactor buildings. During the manufacturing process vinyl chloride is pumped from the tank farm storage area via another storage tank to two reactor buildings. Under conditions of increased temperature and pressure and in the presence of other substances acting as cstalysts and surfactants, polymerization of VCM takes place. The resulting PVC is piped as a slurry to blending tanks and is then dried by centrifuging and rotary drying. The dried polymer is sifted and either removed to storage silos or bagged and stored in the warehouse before being dispatched. The manufacturing process is operated in batches throughout the 24 hours and the workforce is divided into four shifts. In the reactor and dryer buildings men usually start as 'B' operators and can then proceed to be 'A' operators and sometimes 'Lead' operators. , Available data suggest that prior to 1975 levels of VCM in the factory were considerably higher than the current low levels. During the period 1969 -- 1975 "an working in the reactor buildings, and particularly those involved in the manual cleaning of rosetors, are likely to have been exposed to the highest levels of VCM. ucc 027791 51.2.2 The foundry The foundry was situated near the PVC factory in the same industrial alley and manufactured moulded steel products. The manufacturing process involved the production of molten steel which was cast into appropriate moulds to which various finishing techniques were applied. &'*V, ucc 027792 6 2. METHODS 2.1 Selection of the survey population All 177 men currently employed at the PVC factory were invited to take part. The names of another 263 men who had worked at the plant since it started production in 19o9 were identified from factory records and attempts were made to trace and invite all these men using information supplied by the management, union representatives and local records. At the foundry the study was confined to 285 men selected randomly from the 1,085 current male employees. 2.2 The medical survey The factories were visited by the medical survey team and men were 3een by appointment. Details of each man's smoking history were recorded by a trained clerk using a questionnaire which was a modified version of the smoking section of the Medical Research Council Questionnaire of Respiratory Symptoms (MRC, 1976) (see Appendix 1). A full occupational history was recorded for each man by a trained clerk who had previously visited both factories and was familiar with their layout and the manufacturing processes. Details of all jobs which a man had done since leaving school were recorded and the time spent in each of them noted. All PVC factory employees had measurements of forced expiratory volume in one aecond (FEVj), forced vital capacity (FVC) and gas transfer factor for carbon monoxide (Tuco). For foundry workers, approval was ootained for measurement only of Tuco. Measurements of FEVt and FVC were made using an electronic dry rolling-seal spirometer (Ohio 8co). After a practice expiration, three forced expirations which were considered to be technically satisfactory from a maximum of six were recorded. The .. maximum values of TEV1 and FVC, not necessarily in the same breath, were used for the analysis, and the ratio of FEV* to FVC was derived from these figures. UCC 027793 7, Single breath gas transfer factor for carbon monoxide (T-co) was measured by the breathholding method of MEADE et al. (1965) based on the modified Krogh technique- An automated apiroaeter/gaa sampling system (Transfer Test B, P.K. Morgan Ltd., Chatham, Kent) was used and duplicate estimations were made for each man at least 10 minutes apart. Technically unsatisfactory tests were rejected and repeated (i.e. if the inspired volumes of the two teats differed by more than 1(J6, if the spirograms of the manoeuvres were of different shape or if the rates of inspiration and expiration were too slow). The mean of the results of the two satisfactory tests was used in the analysis. Each man was weighed fully clothed and his standing height measured. 2.3 Methods of analysis The data were 3tudiea initially by summary descriptive statistics and multiple linear regression analyses of lung function taking into account age, height, weight and smoking habit. Subsequent examination of the standardised residuals* was carried out and on the basis of this cases and controls were selected. 2.3.1 Classification of smoking histories Men were assigned to one of three smoking categories; lifelons nonsmoker, current smoker and ex-smoker. No distinction was made in the analysis between type of smoking and the two 'smoker' groups included smokers of manufactured cigarettes, hand-rolled cigarettes, pipes and cigars, since the majority of men smoked manufactured cigarettes. 2.3.2 Analysis of data from total survey copulation The distributions of lung function and various explanatory variables * A standardised residual, SR, is the difference between an observed lung function value and its predicted value from multiple linear regression analysis, divided by the estimated standard deviation of the unexplained variation from this model. i e SR * (observed value - value -predicted from fitted equation) (estimated standard deviation of the prediction) uce 027794 8 were examined for systematic patterns amongst current and former employees of the PVC factory and current employees at the foundry. This was further explored for Tuco and FEV^ by multiple linear regression analysis taking account of age, height, weight and smoking. The relationship between a man's observed and predicted values was expressed as a standardised residual (SR). Thus men whose observed values were close to the predicted values would have SR values clustered around zero and correspondingly men with impaired lung function would have the largest negative SR values. The distribution of SR values was examined to see if there was evidence of an unexpectedly large number of men with impaired lung function and if so, to examine if either PVC factory or foundry employees were over represented amongst these men. 2.3.3 Selection of cases and controls For each lung function variable those men with the largest negative SR values were chcsen as cases. Two groups of controls were selected randomly, firstly from those men whose SRs ware clustered around zero and secondly from those with the largest positive SRs. 2*3.^ Case-control study Cases were initially compared with the rest of the survey population in order to identify systematic differences amongst related factors, e.g. age, smoking habit, employment status. 'The occupational and smoking histories of cases and controls were studied for systematic differences, Fisher's exact test, chi-squared tost for 2x2 contingency tables and chi-squared test for linear trend were used where appropriate. Classification of smoking and employment histories Smoking histories were classified as they were for the total population (see Section 2.3.1). Additional information about the number of cigarettes smoked and age of starting smoking was analysed in the casecontrol study. Bread occupational categories were defined for both PVC ucc 027795 9 factory and the foundry (Tables 1 and 2) and the total number of years spent by all cases and controls in each occupational category was calculated. Additional information was available for PVC employees in relation to exposure to emulsion polymer and employment in the factory prior to 1975* Prom tha full occupational history, the number of years in 'noxious' industries was recorded. 'Noxious' industries were classified into four groups; the coal and chemical industries have certain well recognised hazards, while the lung function of men in the steel industry has been reported to be lower than man in non-dusty employment (HIGGINS, 1970); the fourth, designated 'other', included industries in which hazards could possibly arise although they would be les3 liicely than those of the otner groups (see Appendix 2 for a list of 'other noxious' jobs). Employment of men in the manufacturing of PVC other than at the PVC factory was also noted. yjitfs- ucc 027796 10, 3. RESULTS 3.1 Description of total survey population A total of 468 oen was seen consisting of 165 current ?VC factory employees (93& of those who were ashed to participate), 102 PVC factory leavers (395$ of those who were invited) and 221 foundry employees (7&$ of those invited). Three men (one from each employment category) did not complete the Tlco measurement and one foundryman did not have height and weight values recorded; the analysis was based on the remaining 484 men. FEV^ and FVC measure ments were not obtained from three FVC factory leavers and were not carried out on the 221 foundrymen and the analysis was based therefore on 264 men. 3.2 Analysis cf lung function data from total survey population 3.2.1 Calculation of predicted values and standardised residuals The effects of age, height, weight and smoking habit on the Tlco and FEVi were studied in this population by multiple linear regression. The development of the regression model used is described in Appendix 3Standardised residuals (SB) for Tlco and FEV1 were calculated for each man from the final regression model. Thus a man's standardised residual Tlco represents the amount by which his Tlco value differs from that predicted by his age, height, weight and smoking habit after standard isation. 3*2.2 .Distribution of standardised residual values of Tlco and FEY, for total survey population After allowing for the above factors, the standardised residual values of Tlco for the total survey population showed a symmetrical distribution, with no greater number of men in the negative tail of the distribution than would be expected to have occurred by chance. This f indicated that there was no evidence that a substantial number of men had suffered a clinically important reduction of their Tlco. However, for the FEVj^ SB distribution there were slightly more extreme negative values than extreme positive values (Figures 1 and 2). 3-2.3 Selection of cases and controls ; It was decided that about 30 cases would fora a study group of appropriate size. The threshold S3 value for Tlco below which there was approximately this number of ment was -- 1.5. giving 31 men. A ucc 027797 11 control group of 31 men was selected randomly from those men with SB values between - 0.25 and + 0.75 inclusive (Tlco 'average* controls). A second control group of 31 'extra-healthy* men was selected randomly from those with S3 values in excess of + 0.75 (Tuco 'healthiest* controls). Similarly 30 men with an FE7j SB value of less than -1.1 were selected as TSVl cases and two control groups, each of 30 men, were selected randomly from those with an SB value between - 0.25 and * 0.75 inclusive (FEVX 'average' controls) and from those with an SB value in excess of + 0.75 CFEVi 'healthiest' controls). 3*3 General features of cases, controls and the total survey population 3.3.1 Avc. height and weight The mean age, height and weight of Tuco cases and controls, FEV^ cases and controls and the total population are given in Tables 3 and 4. TLco eases and controls were of similar age but cases tended to be taller than the control groups. Although the mean ages of Tlco cases and control groups were similar, study of the age distributions (Table 5) showed an & excess of current PVC factory employees in the 45 - 54 age group when j -compared with both groups of controls and the rest of the population. 4 FEV1 oases were slightly older and taller than the controls and the rest of the population but there was no difference in the age distribution between employment groups or cases and controls. 3*3.2 Employment status and smoking habit The employment status of cases, controls and the total population is shown in Tables 6 and 7* PVC factory employees were slightly over represented amongst Tlco cases but this could easily have occurred by chance. Differences in smoking habit are discussed in a later section. 3*3.3 Lung function The mean values of Tuco for Tuco cases and controls and the total population are ahewn in Table 3 and mean values of Tlco, FEVx and FVC for FEV^ eaaes and controls are shown in Table 4. ucc 027798 12 Observed Tueo and FEVx values were expressed as a percentage of values predicted on the basis of Cotes's regression model (COTES, 1979) and the distribution of these values for cases, controls and the total population are shewn in Tables S and 9* 3.4 Clinical description of Tt-co cases and FEV, eases Fifteen men (nine FVC workers and six foundryraen) of the 31 Tt-co cases had Tuco values below 7C5& of their predicted values and four of these were below (Table 8). Kineteen of the 31 cases were from the PVC factory and of those, four mar. had FEV. values of less than 8CS of their predicted value and low FEVj/FVC ratios indicating airflow obstruction. The remaining 15 "sen had FEVj, values within the normal range although further examination cf their lung function data (forced expiratory flow-volume loops) suggested that seven of these might have mild airflow obstruction. Details of the 10 PVC workers with the lowest Tuco standardised residual values are given in Table 10. Of tbe y) cases, 13 had observed FEVX values below RC& of their orcdicted valuer and 10 of these were less than 7CP6 (Table 9). The majority (10) of the 13 man with reduced FEVt had FE'/1/FVC ratios below 70S suggesting airflow obstruction. Seven of the IZVl cases were also selected as Tlco cases.. 3.5 Ca3e-control study The occupational histories and smoking1 habits of cases and controls were compared in order to explore the observed differences in their lung function. 3-5.1 Occupational histories of cases and controls Analyses of the current employment status of cases and controls showed that PVC factory workers were slightly over-represented amongst the Twco cases (Table 6), though this difference could easily have arisen by chance. The majority of PVC workers had worked in more than one type of job and in more than one broad occupational category during their employment with the company. Analysis of the mean duration of employment in each, broad category failed to show any differences between T-co eases and their UCC 027799 13 controls (Table 1l), though mere cases than controls had worked in jobs in category 1, those occupations close to the pressure vessels where exposures to VCM were mostly likely to have occurred in the past. This difference could easily have occurred by chance, if PVC workers alone are considered but if the foundrymen are included, 11 of 31 cases (35$) had worked in category 1 jobs in the PVC factory, whereas only 10 of 62 controls (16SH) had done the same. The difference is significant at the level. These occupational differences were not apparent for the FEVl cases and controls (Table 13). There was also movement between jobs at the foundry but there were no differences in the pattern of employment cf cases and controls (Table 12). Pre-1975 employment Following the recognition of the hazards of VCM exposure in 1973, levels of VCM in the factory were progressively reduced during 17V and by January 1975 the exposure levels were low. The numbers of cases and controls who had been employed at the PVC fectory before 1st January ' 1975 were compared. Seventeen of the 19 PVC worker Tuco cases had been employed before 1975 compared with five of the 15 'healthiest* * controls and 11 of the 13 average controls (Table 1*0. tfoing a X3 test for trend, there was strong evidence to suggest a significant increase in the proportion of men working before 1975 over 'healthiest' controls, 'average' controls end cases. Looking at comparisons between groups only the difference between cases and 'healthiest' controls was significant. Analysis of the duration of employment of men within different age groups showed that pre-1975 working was seen in younger as well as in older men (Tables 15, 16, 17). No differences were seen in the number of men employed before 1975 between PVC factory FEV'! cases and controls (Table 18). A similar analysis of foundry Ti_co cases failed to show any relationship with pre-1975 employment (Table 19). In conclusion there is evidence to suggest that employment at the PVC factory before 1975 was associated with impairment of Tuco. ucc 027800 14. Exposure to emulsion polymer The employment of cases and controls in the manufacturing of emulsion polymer was studied and compared. Ho man had been exclusively involved in the production of emulsion polymer so men were divided into three groups; those who had worked with suspension polymer only, those who had worked with both suspension and emulsion, and those who had not been exposed to either. Similar proportions of Tlco cases and controls (Table 20) and FEVj eases and controls (Table 21) are represented in each of these three groups. There is no evidence that exposure to emulsion polymer adversely affected the lung function of those who worked with u. Previous employment in other industries There was no evidence that the observed differences between cases and controls could be explained on the basis of previous employment in industries other than the PVC factory or the foundry. Ho differences were found either in the numbers of cases and controls or is the mean numbers of years spent by them working in other industries which might be considered noxious (l.e. coal, steel, chemicals and 'others') (Tables 22, 23, 24). No men had been employed in the manufacturing of PVC outside this PVC factory. 3*5*2 Smoking habits of cases and controls A higher proportion of Tlco cases (636) were current cigarette smokers than were either group of controls (4c&) or total survey population (48) (Table 25). This difference was not seen between the FEVt cases and controls but there were more ex-smokers among the FEVX cases than there were among the controls (Table 26). The smoking histories were examined in greater detail by analysing the number of cigarettes which current cigarette smokers smoked daily both on weekdays and during the weekend, the number smoked by each man during the maximum smoking period of his life and the age at which each man started smoking. There was no significant.difference in the number of cigarettes smoked on weekdays between both groups of cases and the'healthiest' controls (see Figures 3 and 4), and similar results were found for 'average' controls. UCC 027801 15 Analysis of weekend smoking showed that more Tlco cases smoked 25 or fmore cigarettes per day than did the Tt-co healthiest controls (Figure 5)* No such difference was found to exist with average controls. Comparing the weekend smoking habits of PVC factory and foundry Tt-co cases, it was found that a larger proportion of foundrymen smoked mere than 25 cigarettes per day (Figure 5)- For the FEVX men, more cases than average controls smoked 25 or more cigarettes per day at weekends. This difference was not seen between cases and healthiest controls. Consideration of the number of cigarettes smoked during a man's maximum smoking period showed that of the men at the PVC factory, five of the 13 Tuco cases, compared with rone of the six TLco'healthiest' controls had smoked a maximum of ?5 or more cigarettes per day (Figure 6). but this difference in proportions .could easily have arisen by chance. The age at which men started smoking was also examined. There were significant differences between cases and controls. Of the 20 Tuco cases who were current smokers, eignt had started smoking by the age of 15 compared with one out of the 14 'healthiest' controls and 1o had started by the ace of 15 compared with five out of the 14 'healthiest' controls (Figure Pa), while the figures for average controls were that six out of 15 had started smoking b7 the age of 16 (Figure 8b). Of the 13 FEVj cases who were current smokers, seven had started smoking by the sge of 16 compared with two of the 11 'healthiest* controls (Figure 9a). These differences were not seen between cases and 'average' controls (Figure 9b). In conclusion Tuco cases and 'healthiest' controls and FEVX cases and 'average' controls differed in the number of men smoking 25 or more cigarettes per day at weekends. A similar difference was found between Tt-co cases at the PVC factory and the foundry. In general, cases started smoking at a younger age than controls. ucc 027802 16 4. DISCUSSION The present study had two aims. First, to describe the lung function, particularly the Tlco, of current and past employees of a factory manufacturing PVC, and seek evidence of a possible excess of men whose A.CO was abnormally low. Second, to examine the relationship between Tlco and occupation and other personal and environmental factors by a case-control study, in which the eases were men with lowest gas transfer factor after allowing for age, height, weight and smoking habit. Hen from a nearby foundry were included in the study in order to increase the number of men with low or no exposure tc possible respiratory hazards at the PVC factory, but who were exposed to similar environmental conditions outside their workplace. In all 265 men frcm the ?VC factory and 219 men from the foundry were included in the Tlco analysis. The TLco residuals among this combined population conformed approximately to a Normal distribution after allowing for age, height, weight and smoking abit, and did not suggest an undue excess of extremely low values. This ndicated that it was unlikely that a substantial number of men in the hole population were suffering from a clinically important reduction of he Tlco. In the case-control study the 31 men with the lowest Tlco after allowing for age, height, weight and smoking habit were selected as 'cases'. This does not imply that all 31 were suffering from lung disease, but among them were 15 men whose Tlco was less than 7<3> of the value predicted by published normal values, a lovel which would generally be regarded as abnormally low. Among the 19 cases at the PVC factory the pattern of lung function accompanying the low Tlco was that of definite airflow obstruction in four men, and possible airflow obstruction in another seven men, suggesting the presence of emphysema. The remaining eight men did not have evidence of airflow obstruction or reduction of their lung capacity (vital capacity). This pattern is unusual in clinical practice, and may possibly reflect pulmonary fibrosis or disturbances of the blood flow in the lungs. The degree of reduction of transfer factor of carbon monoxide and associated airflow obstruction might have been sufficient to cause breathlessness on exertion in some of these men. ucc 027803 17 The possible contribution of occupation in causing these lung function abnormalities was examined by comparing the occupational histories of the cases with those of controls. Two groups of controls were selected; one group from men with values of gas transfer near the mean for this population; the other group from those with values towards the high end of the range ('average* and 'healthiest' controls). The reasons for choosing two such groups were that men with near average values may have included some whose lung function had been slightly affected by noxious influences, while those with very high values ware least likely to have been affected by noxious influences, but also could conceivably include men who were highly resistant to these influences, and would therefore not be suitable for the comparisons sp.de in this study. The PVC workers were slightly over-represented among the cases with low Tueo, though this difference could easily have arisen by chance. Men who had worked on jobs at the PVC factory which were close to the pressure vessels where exposure to VCM was most likely to have occurred in the past, ware also slightly over-represented among the cases, and this difference approached statistical significance at conventional levels. There was, furthermore, an association between low gas transfer factor and a history of having worksd at the PVC factory before 1975. This date is important because it was at this time that, in the light of information about some of the potential hazards of VCM, exposure to this gas was drastically reduced. This association between low gas transfer! factor and working before 1975 was demonstrated by comparison with the 'healthiest' controls, the 'average' controls showing an intermediate pattern of association not statistically significantly different from the cases. This association with working before 1975 was not found among foundry workers. This conjunction of findings suggests that an unknown environmental or personal factor or factors associated with working at the PVC factory before 1975 might have been responsible for some impairment of the transfer factor in some of these men. The most obvious candidate for suspicion is VCM, exposures to which are known to have ucc 027804 i8 been much higher than post-1975 levels- Some support for this is provided by published case reports of VCF. .workers with impairment of gas transfer factor, but proof of association has been lacking (LAHGE, 1975; DA3KE, 1976). vw>U-r-Tl-Tt17 il' IBILl!- !5S?T^5^^T"es`^Txpo3'ures wouldri though it is possible that many workers throughout the factory were I exposed to a lesser degree. It is also rossible that exposure to 'respirable FVC dust may have contributed to the low gas transfer factors, for this dust has been shown in other studies to be associated with impairment of other aspects of lung function (though not the gas trarsfer factor) and slight chest radiographic abnormalities (KASTfcAHGELO et al., 19^9; SOTTAS et ai., 1980). There was no evidence to suggest that a current risk to respiratory health exists at either the PVC factory or foundry. 2*aSome differences in smoking habit were found between cases and controls ij3non-smokers being slightly commoner among controls, and heavier smokers Hgj slightly commoner among the cases. The cases tended to start smoking at a slightly younger age. b'e do not know if these small differences in smoking habit were sufficient to account for the reductions of gas transfer factor in the cases, but they would seem unlikely to account for the whole of the differences between cases and controls. While the response rate among currently employed workers was excellent, that for those men who had left the PVC factory was low (39K). If the men not examined had included either an excess or deficiency of men with impaired gas transfer factor compared with the population examined', then the analysis of the distribution of values among the population seen could be unrepresentative to that extent. A similar analysis for another lung function test, forced expired volume in one second, was carried out for the PVC workers only. While some men did have impairment of this test result as would be expected in an industrial population of this kind, no associations with occupation could be demonstrated. ucc 027805 19 5. CONCLUSIONS AND RECOMMENDATIONS We found no evidence of an unexpectedly large number of men with impairment of their lung gas transfer factor among either FVC factory or foundry employees. There was, however, a small number cf men in both factories with impairment of their transfer factor. This could not be 3hown to be associated with current working conditions at either factory, but the pattern of results among FVC workers suggested that there was an association between impairment of the gas transfer factor and a history of working in the PVC factory before 1975- There was also evidence that heavy smoking was associated with impairment of gas transfer. These findings give some support to the hypothesis that work in the PVC factory before 1975 involved exposure to a substance that caused impairment of lung function in a small number of men. The results suggest that more detailed studies of the importance of exposure to vinyl chloride monomer, polyvinylchloride, smoking habit and other possible factors in causing impairment of lung function would be desirable, togtther with a clinical assessment of the extent of lung damage in selected men. UCC 027806 .20 ACKNOWLEDGEMENTS This study was carried out with the full co-operation of the management and workforce of Vinatex Ltd., to whom we are grateful for financial support. We also thank the management and workforce of the foundry for their generous co-operation in the study. ucc 027807 21 REFERENCES AGARWAL DK, KAN JL, SRIVASTAVA SP, SETH PK (1978) Some biochemical and histopathological changes induced by polyvinyl chloride dust in rat lung. Environmental Research; 16: 333 - 3**"** ASNADD A, PCMMIEH de SANTI P, GARBE L, PAYAN H, CHASPIN J (1978) Polyvinyl chloride pneumoconiosis. Thorax; 33: 19 - 25. CBIVERS CP, LAWRENCE-JONES C, PADDLE GK (1930) Lung function in workers exposed to polyvinyl chloride dust. British Journal of Industrial Medicine; 37: 1**7 - 151* CORDIER JM, FIEVS2 C, LEFEVRE M-T, SEVR1N A (1966) Acroosteolyse et lesions cutanees'asscciles chez deux ouvriers affeetees au nettoyage d1autoclaves. Cahiers de Kedecine du Travail; hi 14 - 19. COTES JE (1979) Lung function. Oxford: Blackwell Scientific Publications: 369 - 385. CREECH JL, JOHNSON MN (197*0 Angiosarcoma of liver in the manufacture of polyvinyl chloride. Journal of Occupational Medicine; 16: 150 - 151. DARKE CS (1976) Vinyl chloride and the production of PVC (Discussion). Proceedings of Royal Society of Medicine; 69: 280. FRQNGIA N, SPINAZSOLA A, BBCAEELLI A (197*0 Lesioni polmonari sperimentali da inalazione prolungata dl PVC in ambiente di lavoro. Medicina del Lavoro; 65: 321 - 3**2- GAMBLE J, LID S, McMICHAEL AJ, WAXVEILER RJ (1976) Effect of occupational and nonoceupational factors on the respiratory system of vinyl chloride and other workers. Journal of Occupational Medicine; 18: 659 - 670. HIGGINS ITT (1970) Occupational Factors in Chronic Bronchitis and Emphysema. Review. In: Orie NGM, Van Der Lende R, eds. Bronchitis III. Proceedings of the Third International Symposium on Bronchitis at Groningen, The Netherlands. Springfield (HI.); Charles C. Thomas, 1970 : 83 - 99. UCC 027808 22 LANGE CE, JlfeE S, STEIN G, VELTMAN G (1975) Die sogenannte Vinylchlorid-Xrankheit - eine berufsbedingte Syaterasklerose? International Archives of Occupational Health} 32: 1 - 32. LIUS R, ANDERSON H, NICHOLSON WJ, DADM S, FISCHBEIN AS, SELIKOFF IJ (1975) Prevalence of disease among vinylehloride and polyvinyl chloride workers. Annals of New fork Academy of Science; 246: 22-41, LILTS R, ANDERSON H, HILLER A, SELIKOFF IJ (1976) Pulmonary changes among vinyl chloride polymerisation workers. Cheat; 69: (Suppl. Feb.), 299 - 303. HASTRANGELO G, MANNC M, MARCER G, BAETCLUCCI GB, GEHIGNANI C, SALADINO G, SIMONATO L, SAIA 3 (1979) Polyvinyl chloride pneumoconiosis: epidemiological study of exposed workers. Journal of Occupational Medicine; 21: 540 - 542. MEADE F, SAUNDERS MJ, HYETT F, REYNOLDS JA, PEARL N, COTES JE (1965) Automatic measurement of lung function. Lancet; 2: 573 - 575. MRC (1976) Medical Research Council Working Pe-ty on Research into Chronic Bronchitis. Publications Group, Medical Research Council, 20 Park Crescent, London WIN 4AL. KILLER A, TEIRSTEIN AS, CHUANG M, SELIKOFF U (1975) Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride. Annals of New York Academy of Science; 246: 42 - 52. PRODAN L, SUCIU I, PISLARU V, ELEA E, PASOO L (1975) Experimental chronic poisoning with vinyl chloride (monochloroethane). Annals of New York Academy of Science; 246: 159 _ 163. SOUTAR CA, COPLAND IB, THORNLEY PE, HURLEY JF, OTTEHY J, ADAMS WGF, BENNETT B (1980) Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust. Thorax; 35: 644 - 652. SICTU I, DREJMAN I, VELASKAI M (1967) Study of disease caused by vinyl chloride. Medicina del Lavoro; 58: 261 - 271. ucc 027809 23- VELTMAN G, LANGE CE, JTJHE S, STEIN G, BACHNER tj (1975) Clinical mani festations and count of vinyl chloride diaeaaa. Annals of New fork Academy of Science; 246: 6 - 17. VERTKIN fl, MAMONTOV TR (1970) The state of the bronchi and lungs in workers employed in the manufacture of polyvinyl chloride articles. Gigiena Truda i Professional 'nye Zabolevaniya; 14: 29 - 32. TABLE 1 25 Classification of all jobs at Vinatex into six broad occupational groups. Broad occupational group Jobs included in group 1 All men working in reactors 1 and 2 * a Dryer room B operators * * 3 Dryer room Lead, A and a/3 operators 4 Warehousemen, maintenance staff, laboratory staff and drivers *** 5 General staff who visit plant, e.g. shift supervisors and foremen 6 Managesent and office staff * These men are mc.'t likely to have bee.i exposed to high concentrations of VCM in the past. * These wen are involved in the bagging of PVC and are probably exposed to higher concentrations of dust than other workers in the dryer buildings. *** These nen are potentially exposed to all raw materials and products. UCC 027811 TABLE 2 26. Classification of foundry jobs into seven broad occupational groups. Occupational group No Description Jobs included in group 1 Furnace and melt: furnace operator, burner, charger, weirher, skimmer, smelter, sis.man, ladle repairer, concrete liner. 2 Sand and blasting: coremakef, sand tester, sand mixer, shot blaster, core stripper, knock-out, brick maker. 3 Metalwork: driller, grinder, blacksmith, tinsmith, wagon repairer, rope splicer, cupola repairer, maintenance fitter's cate, maintenance fitter, turner, trainee in the training centre, borer, saw repairer, wagon reoairer, milling operator, inspector in machine shop, welder. 4 Generel and other labourer, patternmaker, plater, platelayer, pipe loader, crane driver, driver, cleaner, technician, trainee, pine roller, slinger, quality control, joiner, greaser, inspector, saddler, bricklayer, care inspector, desnateher, hydraulic attendant, shunter, plumber, pipe recorder, runner operator, sawyer, staff, power house attendant, canteen, tool room attendant, electrician, storeman, ore crusher, ram driver, safety officer. 5 Paint and dipping: dipper, paint sprayer, painter and decorator. 6 Casting: caster, manhole maker, socket man, machine moulder. 7 Fettler fettler ucc 027812 TABLE 3 27 Features of Tuco cases, controls and total survey population. Uean (and standard deviations) of age, height, weight and Tlco. Number of men Cases 31 Ti_co Grouos Controls Controls (average) (healthiest) 31 31 population 484 Age (yw) Uean 41.8 (SB) (10.2) 42.3 (12.5) 40.3 (11.3) 42.2 (11.9) Height (cma) Uean 176.1 (SB) (7.1) 174.0 (6.6) 173.9 (5.6) 173.8 (7.0) Weight (kgs) Uean 82.7 (SB) (13.3) 34.9 (18.5) Tlco (ml/min* mm Eg) Uean (SB) ! 22.2 (4.1) 31.8 (2.9) 79.2 (9.5) 37.3 (4.3) 30.2 (12.6) 30.5 (5.9) ucc 027813 TABLE 4 28 Features of FEVj case3, controls and total survey population. Uean (and standard deviations) of age, height, weight, Trco, FEVj and FVG. Kuaber of men Cases 30 Tlco Groups Controls Controls (average) (healthiest) 30 30 Lorar survey population 264 Age (yrs) Kean 43.3 (3D) (11.0) 41.3 (12.5) Eei^rt (cms) Uean 176.0 (SB) (7.4) 174.5 (6.6) Weight (Ugs) Mean 82.2 (SD) (13-3) 78.4 (10.1) FEVj (litres) Uean (SD) 2.7 (0.7) 3.9 (0.7) FTC (litres) Uean (SD) 4.1 (0.9) 5.1 (0.8) Tuco Uean (ml/min^cnnHg) (SD) 29.1* (6.8)* 32.3 (6.0) 42.1 (12.0) 175.9 (8.0) 80.4 (11.5) 4.5 (0.8) 5-9 (0.9) 31.3 (6.5) 42.2 (11-8) 174*3 (7-1) 80.4 (12*3) 3.7 (0.9) 4-9 (1.0) 30.5** (6.1)** * Value Based on 29 observations. ** Value based on 262 observations. ucc 027814 .:* t TABUS 5 Age distribution of Tuso esses and controls and th total survey population by employment status* CASES PVC currant men PVC leavers Foundrymen AVERAGE CONTROLS PVC currant nen PVC leavers Foundrymen HEALTHIEST CONTROLS PVC current nen PVC leavers Foundrymen TOTAL POPULATION PVC current men PVC leavers Foundrymen Age ranges in years 0 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65+ Total 1 4 11 2221 1 8 1 434 12 141 3 1 12 3 2 54 4 9 4 18 2 3241 12 1 2643 12 3 16 9 5? 57 35 26 0 164 4 24 33 19 11 10 101 1? 48 50 60 44 0 219 $ 027815 TABLE 6 30 Employment status of Tlco eases, controls and total surrey population. Number of men in each employment group with percentages' in brackets. Four men excluded, see text. PVC Current Workers Total surrey population 164 PVC Learers 101 Foundry !Total 219 4fl4 Cases Controls (arerage) Controls (healthiest) All 11 ( 3*0 8 ( 53) 12 ( 26) 9 ( 28) 4 ( 27) 18 ( 39) 12 ( 33) 3 ( 20) 16 ( 35) 32 (ICO) 15 (100) 46 (100) 31 31 31 93 TABLE 7 Employment status of FEVt cases, controls and total surrey population. Number of men in each employment group with percentages in brackets. Three men excluded, see text. Rounding error of percentages not adjusted to justify totals. Total surrey population PVC Current Workers 165 PVC Learers 99 Total 264 Cases Controls (arerage) Controls (healthiest) All 14 ( 26) 18 C 34) 21 ( *40) 53 (100) 16 ( 43) 12 ( 32) 9 ( 24) 37 (100) 30 30 30 90 ucc 027816 TittTiij 8 Distribution of observed Tuso an a percentage of predicted Ttco ualng Cotea'a regreaaion nodal for non-smokers. Numbers of men (percentages in brack at a) for the oases, two control groups and total survey population. Cases 49 Controls (average) Controls (healthiest) Total survey population Tt.00 % predicted Total 50 - 59 60 - 69 70 - 79 80-89 90 - 99 100 - 109 110 - 119 >, 120 4 (12.9) 11 12 (35.5) (38.7) 4 (12.9) 11 (35.5) 13 (41.9) -3 (9.7) 31 7 (22.6) 14 (45.2) 31 14 31 (45.2) 4 (0.8) 14 (2.9) 29 (6.0) 75 114 (15.5) (23.6) 120 (24.8) 82 (18.9) 46 484 (9*5) ucc 027817 TABLE 9 Distribution of observed FEV, ao a p omentags of predicted FEV, using Cotes'a regression model for non-smokers. Numbers of non (percentages in brackets) for the oases, two control groups anl total survey population. t-- t o ucc 027818 *19 50-59 60 - 69 F3V, % predicted 80-89 90 - 99 100 - 109 110 - 119 \ 120 Total Cases 1 (3.3) 4 (13.3) 5 3 14 (16.7) (10.0) (46.?) 3 (10.0) 30 Controls (average) 3 17 (10.0) (56.7) 91 (30.0) (3.3) 30 Controls (healthiest) 1 (3.3) 6 23 (20.0) (76.7) 30 Total aurvey 1 population (0.4) 4 ( 1.5) 6 (2.3) 9 29 (3.4) (n.o) 48 74 (18.2) (28.0) ______ 47 46 (17.8) (17.4) 264 TABLE 10 Patella of the 10 PVQ factory TLno oases with the lowest standardised residual values of Tl.oo. Cass No. 1 did net complete the spirometry Uat. Predicted values are for non-amokera (Cotes, 1979), Ho* Asa Saoking category SB It CO Tuco Tteo 3 FEtfj litres litres ysr&-- TKT- rev (observed) (cradleted) cradle tad (obaerved) (predicted) eradiated lltree 100 1 30 - 34 0 - 2.89 2Q.1 34.6 18.3 - - --- 2 65 - 69 E - 2.75 14.1 27.4 51,3 2.1 3.0 69.8 3.8 55.2 3 35-39 C - 2.22 20.1 31.8 63.5 3.6 3.8 95.2 5.2 68.9 * 40 - 44 E - 2.15 20.9 30.5 68.4 1.2 3.3 34.3 3.5 35.1 5 35-39 C - 2.11 20.0 >2.1 64.6 3.2 3.8 84.9 4.1 77.9 6 55-59 0 - 2.02 14.7 23.9 61.4 2.6 2.7 95.5 3.3 77.9 7 50 - 54 a a 35 - 39 ' c - 2.01 15.4 - 1.99 23.3 25.9 35.5 59.5 65.6 2.7 4.2 3.0 90.6 4.3 62.2 4.1 101.7 5.7 74.3 9 45 - 49 N - 1.92 22.5 29.2 77.0 4.1 3.4 120,1 5.1 60.0 10 50 - 54 c - 1.84 16.8 29.0 64.8 3.G 3.3` 107.9 4.7 75.8 The abbreviations of snaking categories are as follows! C a current anokor E a Ex-anoker Tlco units ars ml/nin, am Hg. M a life-long non-saokar 34 TABLE 11 PVC factory Ttco cases and controls. Mean tines (years) spent in each occupational group with number of men in brackets. See Table 1 for key to occupational groups. Amongst these cases and controls, the only man who had spent time in occupational group 6 wasa current employee, selected as one of the 12 'healthiest' controls. He h d spent 1.7 years in this group. cases Current men Leavers Number of men 11 8 AVERAGE CONTROLS Current men Leavers 9 4 HEALTHIEST CONTROLS Current men Leavers 12 3 1 3.7 (6) 1.6 (5) 9.1 <3) 0.7 (1) 3.3 <5) 1.5 (1) . Occupational groups 2 3< 5 0.4 6.1 9.0 9.7 (5) (3) (4) (2) 0.8 11.8 (6) (1) - - 1.1 6.8 7.1 12.3 (3) (1) (4) (1) C.4 (4) - 1.8 CD - 1.2 10.8 7.3 3.3 (8) CD (2) (2) 0.5 (3) - - ucc 027820 TABLS 12 35- Foundry Ttco cases and controls. Mean times (years) spent in each occupational group with number of men in brackets. See Table 2 for key to occupational groups. Number Occupational groups of men 1 2 3 4 5 67 CASES 12 7.3 3.0 12.3 4.0 3.2 11.4 1.0 (4) (2) (5) (7) (2) (2) (D AVERAGE CONTROLS 18 4.6 16.1 30.4 (3) C5> (1) 9-4 (9) HEALTHIEST CONTROLS 16 13.4 (5) 4.5 (3) 12.7 (3) 12.5 (8) 7.4 io.6 2.5 (13 (5) (D 11.6. - (6) - I TABLE 13 PVC factory rEV^ cases and controls. Kean times (years) spent in each occupational group with number of men in brackets. See Table 1 for key to occupational groups. . Number of men 1 Occupational groups 2 34 5 6 CASES Current men Leavers 14 5.5 1.3 4.3 6.1 6.8 3.8 (7) (8) (2) (6) (2) (1) 16 2.1 0.8 4.7 (8) (<?) (3) 1.0 - (2) - AVERAGE CONTROLS Current men Leavers 18 3-2 .1.2 (10) (10) 12 1-3 0.9 - (5) (7) HEALTHIEST CONTROLS Current men 21 6.4 1.Z CiO) (10) Leavers 9 1.2 0.3 <2) (6) 5*2 (13 4.1 (3)- 0.7 (2) - 7.6 7.7 5.0 (5) (2) (2) - 1.2 3.1 - (3) (2) 7.2 3.6 2.6 (9) (3) (2) 2i1 (2) - - ucc 027821 TABLE 14 For Tu:o analysis, the distribution of numbers of PVC cases and controls who had worked at the FVC factory before 1975 and only after 1975- Pre 1975 Post 1975 Total Cases 17 2 Average Healthiest Controls Controls 11 5 Z 10 L_Jf_____ 13 15 Total 33 14 47 TABLE 15 PVC factory Tu:o cases. Number of men within each age group and duration of pre-1975 employment category. Tice of employment Duration of employment 0-24 25 - 34 Age (yrs) 35-44 45 - 54 55 - 64 -----------j 1 Total 65 + < 2 yr 1 341 9 Pre 1975 2 - 4 yr 12 3 > 4 yr 4 15 Post 1975 - 1* 1 2 Total 1 2 6 8 1 1 19 UCC 027822 37 TABLE 16 PVC factory Tuco average controls. Number of men within each age group and duration of pro-1975 employment category. Time of anployment Iteration of employment 0 - 24 25-34 Age (yrs) 35-44 45-54 55 - 64 65 + Total Pro 1975 Post 1975 Total < 2 yr 2 - 4 yr > 4 yr - 112 21 1 12 11 2533 4 3 4 2 13 TABLE 1? PVC factory TLco healthiest controls. Number of men within each age group and duration of pre-1975 employment category. Time of . anployment Duration of employment 0-24 25 - 34 Age (yra) 35-44 45 - 54 55 - 64 I1 ' Total 55 + Pro 1375 < 2 yr 2 - 4 yr > 4 yr 1 1 1 11 Post 1975 - 232 3 Total 3 52 41 2 A1 2 10 15 ucc 027823 38 TABLE 18 For FEV! analysis, the distribution of numbers of PVC eases and controls who had worked at the PVC factory before 1973 and only after 1975* Pre 1975 Post 1975 Total Casas 23 7 30 Average Healthiest Controls Controls 18 19 12 11 30 30 Total 60 30 90 TABLE 19 For Tlco analysis, the distribution of numbers of foundry cases and controls who had worked at the foundry before 1975 and only after 1975. Pre 1975 Post 1975 Total Cases 8 4 12 Average Healthiest Controls Controls 13 12 54 18 16 Total 33 13 46 ucc 027824 TABLE 20 39 For Ttco analysis* the distribution of PVC factory cases and controls who had worked with different polymers. Cases Average Controls Healthiest Controls Total Emulsion and suspension Suspension only Neither suspension nor emulsion 6 9 4 8 4 18 3 11 23 2 06 Total 19 13 15 47 TABLE 21 For FEV^ analysis, the distribution of PVC factory cases and controls who had worked with different polymers. Cases Average Controls Healthiest Controls Total Ekmlsion and suspension 8 7 10 25 Suspension only 18 13 13 44 Neither suspension nor emulsion 4 10 7 21 Total 30 30 30 90 ucc 027825 TABLE 22 AO, PVC factory Teco cases and controls. Number of men who have worked in noxious occupations with mean number of years spent by these men in brackets. See Appendix 2 for list of 'other' noxious occupations. CASES Number of men 19 AVERAGE CONTROLS HEALTHIEST CONTROLS 13 15 Steel 8 (5.5) Noxious occupations Chemicals Coal T (1.9) 7 (10.1) 03 6 (9.6) (6.9) 3 (6.1) 0 - 2 (17.4) Other 8 (11.5) 7 (10.4.) 8 (7.1) a*#* TABLE 2J PVC factory FSV. cases and controls. Number of men who have worked in noxious occupations with mean mmber of years spent by these men in brackets. See Appendix 2 for list of 'other' noxious occupations. CASES Number of men 30 Steel Noxious occupations Chemicals Coal 10 (4*6) 5 (4.0) 16 (15.7) Other 16 (13.2) AVERAGE ' CONTROLS 30 7 6 9 15 (9.8) (14.0) (6.3) (7.5) HEALTHIEST 30 4 CONTROLS (17.8) 4 (9.1) 11 (I3.fi) 18 (8.9) IJCC 027826 TABLE 24 4l Foundry Tuco cases and controls. Number of men who have worked In noxious occupations with mean lumber of years spent by these men In brackets. See Appendix 2 for list of 'other' noxious occupations. Number of men Steel Noxious occupations Chemicals Coal Other CASES AVERAGE! comoLs 12 1 (3-0) 18 2 (9-6) 0 (0.0) 0 (0.0) 3 (5.4) 5(1*3) 4 (9.0) a (10.9) HEALTHIEST CONTROLS 16 2 (4*7) 0 (o.o) 5 (2.9) 5 (7-2) 1 ucc 027827 TABLE 25 Smoking habits of Tlco cases, controls and total survey population* Number of men in each umpiring category with percentages in brackets. NonSmoker Current Smoker Ex-Smoker Total Cases 3 (9.7) 20 (64.5) 8 (25-8) 31 Controls (average) 4 (12.9) 15 (48.4) 12 (38.7) 31 Controls (healthiest) 7 (22.6) 15 (48.4) 9 (29-0) 31 Total survey population 109 (22.5) 234 (48.4) 141 (29-1) 484 TA3T.B 26 Smoking habits of ESTj cases, controls and total survey population. Number ox men in each smoking category with percentages in brackets. Cases Controls (average) Controls (healthiest) Total survey population NonSmoker 5 (16.7) Current Smoker 13 (43.3) 7 (23.3) 15 (50.0) 9 (30.0) 12 (40.0) 59 (22.3) 125 (47-4) o o* CM fix-Smoker Total 30 8 (26.7) 30 9 (30.0) 30 80 (30.3) 264 ucc 027828 *0. ucc 027829 Number of man 45 Fig. 3 Number of cigarettes smoked or weekdays by FEVj cases and 'healthiest' controls who are1 current smokers. Fig. 4 Number of cigarettes smoked on weekdays by Tico cases and 'healthiest' controls, at the PVC factory and the foundry, who are current smokers. ucc 027330 PVC factory BFoundry 8 5 4 3 2 1 a. Cases 50 + No. Of ClgS. FI*. 5 Number of cigarettes smoked per day at weekends by Tlco cases and 'healthiest' controls, at the FVC factory and the foundry, who are current smokers. ucc 027831 fc9. Fig. 6 Maximum number of cigarettes regularly smoked per day by Tlco cases and 'healthiest' controls, at the PVC factory and the foundry, who are current smokers. Fig. 7 Maximum number of cigarettes regularly smoked per day by FEV^ cases and 'healthiest' controls. ucc 027832 51 (*) (b) 'healthiest'---------------------------factory and the foundry, who are currant smokers. who ara currant smokers. U) (b) Fig. 9 a) Aga whei started smoking cigarettes, for FEV, eases and 'healthiest' controls, who art currant smokars. b) Aga whan started smoking cigarettes, for FEV. eases and 'average' controls, who are ttirrent smokers. ucc 027833 53. APPENDIX 1 SMOKING COESTIONNAIPE 1 Do you amok*? If NO la Hava you aver smoked as much as ona cigarette a day (or ona cigar a week or as ounca of tobacco a month) for as long as a year? If NO to both parts of quaatios 1, omit remaining questions on smoking. 2 How old ware you when you started smoking regularly? 3 How old are you now? 4 Do (did) you smoke manufactured cigarettes? If US ha How many do (did) you usually asoka per day on weekdays? 4b How many do (did) you usually smoke per day at weekends? 4c What was the greatest number of cigarettes you ever saokad regularly per day? 4d for how long ware you smoking that many? 4a Since starting smoking tobacco have there been periods during which you did act smoke cigarettes? If TES, for how long altogether were you not sacking cigarettes? 4f (Apart from those times) what was the least number of cigarettes you ever smoked regularly per day? 4g For how long were you amoking that sany? 5 Do (did) you sooka hand-rolled cigarettes? If US Jm How much tobacco do (did) you usually amok# par weak in this way? UCC 027834 APPENDIX 1, page 2 3*. 6 Do (did) you smoke a pipe? if ns 6a How much pipe tobacco do (did) you usually smoke per week? 7 Do (did) you smoke small cigars? If YES 7a How many of these do (did) you usually smoke per week? 8 Do (did) you smoke other cigars? If YES 3a How many of these do (did) you usually smoke per week? For ex-smokers: 9 When did you last give up smoking? ucc 027835 APPENDIX 2 NOXIOOS OCCUPATIONS In the classification of noxious occupations the following jobs were included in the category 'other'. Although it is recognized that some of the jobs included in this category are not widely recognized as 'noxious', it was considered that they may on occasions be associated with health hazards and should therefore be included in the classification of noxious occupations Brewing . Baker Flour miller Farm worker Woed cutter/sawmill worker Construction worker Bricklayer Plasterer Quarryman Paper mill worker Electrician Joiner Qlassworker Welder Scrap burner Foreman Coking plant worker Furnace operator Car body reoairer Paint sprayer . Painter/decorator Tarmacadam exposed workers UCC 027836 56. APPENDIX 3 Development of the multiple linear regression model used in the analysis of the data from the total survey population Preliminary multiple linear regression analysis indicated the anticipated relationship between Tlco and age, height and weight and between FE7X and age and height. These relationships were looked at again after allowing different intercepts and age slopes for non-smokers and all smokers whether current or ex-smokers. For the Tlco analysis, this was a significant improvement in the amount of variation explained. However, thi3 group of smokers did not have a significantly lower mean Tlco after age, height and weight had been taken into account than non-smokers and the age slopes were similar. The model used for T<-co (but not the FVX model) was further improved by introducing different intercepts and age slopes for three categories of smoking, non-scokers, current smokers and ex-smokers. This analysis showed that for ex-smokers the mean valnn of Tlco was significantly higher than that of current smokers (P < 0.05) but that they experienced a greater loss of Tlco with age than current and non-smokers although these differences were not statistically significant (Table 1). Further expansion of this model by allowing different intercepts and age slopes for -the different employment categories (current and farmer employees at the PVC 'factory and foundry employees) within the three smoking groups did not make a significant improvement to the model. However, this analysis did indicate that the mean Tlco level for leavers from the PVC factory who were current smokers was significantly lower (P < 0.1) Jthan current PVC factory employees who were non-smokers. However, the age slope of this group did not differ significantly from that of current PVC factory employees who were non-smokers. Hence the model used was the one in which different intercepts and age slopes were allowed for the three smoking groups. For reasons of consistency the FEVX analysis was also based on this same model although there was no significant improvement in the amount of variation explained as there had been for the Tlco analysis. The results for FEVj analysis show that there was a significant difference (P < 0.1) in the rate of loss of FEVX with age between non-smokers and current smokers who experienced a greater rate of loss of FEVX (Table 2). UCC 027837 APPENDIX 3, page 2 TABLE 1 57. Regression for Tl.co (ml/min. mm Hg) allowing different intercepts and age slopes for three smoking groups. Variables Ago Height Weight Units Tears GB kg Mean 42. a 173.8 80.2 Constant for non-smokers Regression coefficient -0.2246 0.1552 0.0572 Constants (interceots) 10.3052 t -5-74 4*74 3.23 P < 0,001 < 0.001 < 0.002 Effect on intercept of: Current smokers Ex-smokers -2.5288 t.4554 -1.34 0.6? NS NS Effect on age slope for: Current smokers Ex-smokers -0.0154 -0.0537 -0.33 -1.08 NS ' NS . ta'Bt.s 2 Regression for PE7t (C) allowing different intercepts and age slopes for three smoking groups. Variables Age Height Weight Units Tears cm kg Kean 42.2 174.3 80.4 Constant for non-smokers Regression coefficient -0.0309 0.0420 ' 0.0003 Constants (intercepts) -2.1725 t -4.55 7.13 0.09 P' < 0.001 < 0.001 NS Effect on intercept of * Current smokers Ex-aaokera 0.4209 0.2675 1.24 0.75 NS NS Effect on age slope for: Current smokers Ex-smokers - . -0.0149 -0.0096 -1.81 -1.13 < 0.10 NS UCC 027838 ucc 027839