Document YGrr3DLexG5XBGQjMY67OamKk

R&S 002597 REPORT NO. TM/82/4 UDC 612.2 : 678.743 M'SSinJ^ -f>C(W OWjii0At_ po^t-s . ZHy 4M, %, Hi 5b SZ. AN EPIDEMIOLOGICAL STUDY OF THE LUNG FUNCTION OF -CKXESS AT A FACTORY MANUFACTURING POLYVINYLCHLORIDE by HH Lloyd S Gauld L Copland CA Soutar JANUARY 1982 R&S 002598 INSTITUTE 0 F OCCUPATIONAL MEDICINE AN EPIDEMIOLOGICAL STUDY OF THE LUNG FUNCTION OF WORKERS AT A FACTORY MANUFACTURING POLYVINYLCHLORIDE by MH Lloyd, 3 Gauld, L Copland, CA Soutar Medical Branch Institute of Occupational Medicine, Roxburgh Place, EDINBURGH EK8 9SU. (Tel. 031 667 5131) JANUARY 1982 (ii) CONTENTS Page No. ABSTRACT (iv) 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 . 1 1 2 2 3 3 4 5 R&S 002599 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.^ Case-control study .... 6 6 6 7 7 7 8 8 3. RESULTS.......................................................................................... 3.1 Description of total survey population 3.2 Analysis of lung function data from total survey population ...................................................... 3.2.1 3.2.2 3.2.3 Calculation of predicted values and standardised residuals . . Distribution of standardised residual values of T^co and FEVt for total survey population ..... Selection of cases and controls 3.3 General features of cases, controls and the total survey population ..... 3.3.1 Age, height and weight ... 3.3.2 3.3.3 Employment status and smoking habit Lung function ...... 10 10 10 10 10 10 11 11 11 11 (iii) Page No. 3*^ Clinical description of T*.co cases and FEVt cases 3*5 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 ACKNOWLEDGEMENTS REFERENCES TABLES FIGURES APPENDICES CO 1oo0 o> o o R&S 002601 Report No. TM/82/4 (iv) INSTITUTE OF OCCUPATIONAL MEDICINE AN EPIDEMIOLOGICAL STUDY OF THE LUNG FUNCTION' OF WORKERS AT A FACTORY MANUFACTURING POLYVINYLCHLORIDE by MH Lloyd, S Gauld, L Copland, CA Soutar ABSTRACT We 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 single breath transfer factor for carbon mcnoxide (Tlco). 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 Tlco 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 Tlco 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 Tlco; and a case-control study. In this, men with the lowest Tlco 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 Tlco. The 31 m n select d as 'cases' included 15 men whose Tlco was abnormally" low (less than ?do of published predicted values), of whom ane*~ were PVC workers and were foundrymen. Among the 1 cas s working at the PVC factory the pattern of R&S 002602 () accompanied by evidence of airflow bstruction 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 wore 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 Ti_co 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 chlcride monomer was drastically reduced, in the 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 TUco 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 ether causative factors would be desirable, together with a clinical assessment of the lung damage in selected men. 1. INTRODUCTION The health of workers employed in the manufacture of polyvinylchloride (PYC) has been a cause of concern during recent years. Some adverse effects of exposure to vinyl chloride monomer (VCM) are well recognized, but lung disease in man has net been shown tc be related to exoosure to VCM. Exposure to airborne PVC dust, however, has been shown to cause slight impairment of lung function and slight chest radiographic abnormalities. R&S 002603 Vinvl chloride is the basic raw material used in the production of ?VC. 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. CCROIEP. (''9^3;- v;as the first to describe acro-osteolysis in reactor cleaners in Belgium and in the following year SUCIU (1967) described Raynaud's phenomenon among workers in a ?VC factory. Changes in the skin and internal organs `were subsequently recognised tnd in 197** the term 'vinyl chloride disease' was used to describe the 3yndrcme which has many features in common with scleroderma (VELTKAN "t al., 1975)* The hepatic effects of exposure to VCM have aroused the most interest and include ncn-nalignant changes. It was the discovery of the association between vinyl chloride exposure and angiosarcoma of the livr (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 million (ppm) and an eight-hour time weignted average (TWA) of 10 ppm. In 1?S0 the permitted maximum exposure was reduced to an annual average of 3 ppm. 1.1 Respiratory 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 th potential respiratory effects of these comro'inds. 2 1.1.1 Animal studies The toxicity of both VC and FVC has been investigated in animal experiments. PRODAN et al, (1975) exposed guinea pigs to 1C& 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 the 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 oultinucleated . giant cells developed. Similar giant cells and histiocytes were identified in the alveoli of the lungs of small mammals which were kept in the bagging area of a PVC factory (FRQNGIA 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. ABNADD et al. (1973) studied a 53-year-old man who had worked for 25 years in the bagging plant of a PVC factory. His chest X-ray showed microncdular shadowing and lung biopsy revealed 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. Eis disease was probably related to PVC dust rather than VCM* R&S 002604 DARKE (1975) investigated 1*t- men who nad 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 as being impaired but no measurements or details of other lung function t sta are given. Lung biopsy from one of the men showed focal alveolar wall thickening and macrophages present in alveolar spaces. LANGE t al. (1973) described some cases of VC workers with impairm nt of transfer factor for carbon monoxide, but the relationship with occupation was not clear. 3 1*1.5 Epidemiological studi s 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. (1975) 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. VERTKIN 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 293 ware exposed to a mixt'^re of both. Ho differenc 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 those men* A study of 8l8 men currently and previously employed at a PVC manufacturing plant (SCUTAR 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 tests of lung function among men with the highest PVC dust exposure, and some of these men had small rounded opacities on their hest radiographs. The non 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* R&S 002605 1.2 The present study The present study was request d by Vinatex Ltd., and was carri d out with the full agreement of management and workforce, arid arose from their R &s 002606 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 PVC 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, occuoational and environmental factors. The total survey population included the workforce of two factories; one was the PVC factory of interest and the other was a large iron foundry situated a few hundred yards away. 1.2.1 The PVC 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 - 1974) emulsion polymer, which has a smaller particle size than suspension polymer, 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 catalysts 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 cf VCM in the fact ry were considerably higher than the current low 1 vels. During the period 1969 -- 1975 men working in th reactor buildings, and particularly those involved in the manual cleaning of reactors, are likelv to have bee^ 5. 1.2.2 Th foundry The foundry was situated near the PVC factory in the same industrial valley 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. R&S 002607 R&S 002608 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 seen 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 second (FEV\), forced vital capacity (FVC) and gas transfer factor for carbon monoxide (Tico). For foundry workers, approval was ootained for measurement only of ft-co. Measurements of FEVt and FVC were made using an electronic dry rolling-seal spirometer (Ohio 800). After a practice expiration, three forced expirations which were considered to be technically satisfactory from a maximum of six were recorded. The maximum values f FEVj^ and FVC, not necessarily in the same breath, were used for th analysis, and th ratio of FEVt to FVC was deriv d from th se figures. R&S 002609 7. Single breath gas transfer factor for carbon monoxide (Ti-co) was measured by the breathholding method of MEADE et al, (1965) based on the modified Krogh technique. An automated spirometer/gas sampling system (Transfer Test B, P.lt. 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 tests differed by more than 1C&, 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 studied 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 cas s and controls were selected. 2.3*1 Classification of smoking histories Men were assigned to one of three smoking categories; lifelong non* smoker, current smoker and ex-3moker. No distinction was made in th analysis between type of smoking and the two 'smoker* groups included smokers cf 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 population 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 ouation) (estimated standard deviation f the prediction) 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 fwco and FEVl by multiple linear regression analysis taking account of age, height, weight and smoking. R&S 002610 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 hav the largest negative SR values. The distribution of SR values wa3 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 were clustered around zero and secondly from those with the largest positive SRs* 2*3.4 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 histori s wer classified as they were for the total population (see Section 2*3.t)* Additional information about the number of cigarettes smoked and age of starting smoking was analysed in the casecontrol study. Bread occupational categories w re defined for both PVC 9 factory and the foundry (Tables 1 and 2) and th total numb r 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* From the 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 recognized hazards, while the lung function of men in the steel industry has been reported to be lower than men in non-dusty employment (HIGGINS, 1970); the fourth, designated 'other', included inclustri c iu which hazards could possibly arise although they would be less likely than those of the otner groups (see Appendix 2 for a list of 'other noxious' jobs). Employment of men in the manufacturing of PVC oth r than at the PVC factory was also noted. R&S 002611 .10 3. RESULTS 3.1 Description of total survey population A total of 488 men was seen consisting of 165 current PVC factory employees (9% of those who were asked to participate), 102 PVC factory leavers (39# of those who were invited) and 221 foundry employees (78$ 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. FVX 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 of 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 FEVj^ were studied in this population by multiple linear regression. The development of the regression model used i3 described in Appendix 3* Standardised residuals (SR) for Taco and FEVt 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 FEV, 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 indicated that there was no evidence that a substantial number of men had suffered a clinically important reduction of their Tlco. However, for the FEV^ SR distribution there were slightly more extreme negativ values than extrem positive values (Figur s 1 and 2). 3.2.3 S lection of cas s and controls ; It was decided that about 30 cases would form a study group of ft>\. * _V-, , - R&S 002612 11 control group of 31 men was selected randomly from thos men with SR values between - 0.25 and + 0.75 inclusive (Tuco 'average' controls). A second control group of 31 'extra-healthy' men was selected randomly from those with SR values in excess of + 0.75 (Tlco 'healthiest' controls). Similarly 30 men with an FEYj SR value of less than -1.1 were selected as FEVj cases and two control groups, each of 30 men, were selected randomly from those with an SR value between - 0.25 and + 0.75 inclusive (FEVj 'average' controls) and from those with an SR value in excess of + 0.75 (5,EV1 'healthiest' controls). 3*3 General features of cases, controls and the total survey population 3.3.1 A<?e, height and weight The mean age, height and weight of Tlco cases and controls, FEVX cases and controls and the total population are given in Tables 3 and 4. Tlco cases 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 - age group when compared with both groups of controls and the rest of the population. PEVj cases were slightly older and taller than the controls and the rest ox* the population but there was no difference in the age distribution between employment groups or cases and controls. R&S 002613 33.2 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 Tt-eo 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 Tt-co for Tlc cases and controls and the total population are shewn in Tabl 3 and mean values of Tuco, FEV1 and FVC for 12 Observ d Tuco and FEJVj values were expressed as a percentag of values predicted on the basis of Cotes's regression model (COTES, 1979) end the distribution of these values for cases, controls and the total population are shown in Tables 8 and 9* 3.4 Clinical description of Tuco cases and FEV, eases Fifteen men (nine F'/C workers and six foundrymen) of the 31 Tuco cases had Tuco values below 7C5& of their predicted values and four of these were below 6<$ (Table 8). Nineteen of the 31 cases were from the PVC factory and of those, four men had FEV. values of less than 8C& of their predicted value and low FEVj/FVC ratios indicating airflow obstruction. The remaining 15 men had FEVj^ values within the normal range although further examination of 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 the 30 FEV! cases, 13 had observed FEVj values below 8<3t of their uredicted valuer and 10 of these were less than 7C& (Table 9). The majority (10) of the 13 men with reduced FEV1 had FEV1(/FVC ratios below 7C& suggesting airflow obstruction. Seven of the FE'^ cases were also selected as Tuco cases.. 3.? Case-control study The occupational histories and smoking 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 Tuco cases (Table 6)t though this difference could easily have arisen by chance. R&S 002614 The majority of PVC workers had work d in mor than one type of job and in mor than on broad occupational cat gory during th ir employm nt with the company. Analysis of the mean duration of employment in each broad category failed to show any differences between Tuco cases and their R&S 002615 13 controls (Table 11), though more 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 J1 cases (35^) had worked in category 1 jobs in the PVC factory, whereas only 10 of 62 controls (l6&) had done the same. The difference is significant at the 7% level. These occupational differences were not apparent for the TZ'Ji cases and controls (Table 13). There was also movement between jobs at the foundry but there were no differences in the pattern of employment of cases and controls (Table 12). Pre-IQ1?*} employment Following the recognition of the hazards of VCM exposure in 1973, levels of VCM in the factory were progressively reduced during 1Q7^ and by January 1975 the exposure levels were low. The numbers of cases and controls who had been employed at the FVC factory before 1st January ' 1975 were compared. Seventeen of the 19 PVC worker Ttco cases had been employed before 1975 compared with five of the 15 'healthiest' controls and 11 of the 13 average controls (Table 1*0. Using a 3^ te3t for trend, there was strong evidence to suggest a significant increase in the proportion of men working before 1975 over 'healthiest* controls, 'average' controls and 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 wall as in older men (Tables 15, 16, 17) No differences were seen in the number of men employed before 1975 between PVC factory FEVl cas s and controls (Table 18). A similar analysis of foundry Ti_co cases failed to show any relationship with pre-1575 employment (Table 19). In conclusion there is evidence to suggest that employment at the PVC factory before 1975 was associated with impaina nt of Ti_c . 14 Exposure to emulsion polymer The employment of cases and controls in the manufacturing of emulsion polymer was studied and compared* No 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 cases and controls (Table 21) are represented in each Jfcof these three groups. There is no evidence that exposure to emulsion SHpol.yrr.er adversely affected the lung function ox those who worked with R&S 002616 Frevjous 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. No differences were found either in the numbers of cases ana controls or in the mean nunbeis of years spent by them working in other industries which might be considered noxious (_.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 Ti-eo cases (65#) ware current cigarette smokers than were either group of controls (43#) or total survey population (48#) (Table 25)* This difference was not seen between the FEV* cases and controls but there were more ex-smokers among the FEVl 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 weekendt the number smoked by each man during the maximum smoking period of his life and the age at which each man started smoking* Th re was no significant differenc in the number of cigarettes smok d on we kdays between both groups of cases and the'healthiest* controls (see 15 Analysis of weekend smoking showed that more Tlco cases smoked 25 or more cigarettes per day than did the Tuco healthiest controls (Figure 5). No such difference was found to exist with average controls. Comparing the weekend smoking habits of PVC factory and foundry Tuco cases, it was found that a larger proportion of foundrymen smoked mere than 25 cigarettes per day (Figure 5). For the FFVj 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 Tuco'healthiest' controls had smoked a maximum of 25 or more cigarettes por 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 Tlco cases who were current smokers, eignt had started smoking by the age of 15 compared with one out of the 14 'healthiest' controls and 16 had started by the age of 16 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 by the age of 16 (Figure 8b). Of the 13 FEVj cases who were current smokers, seven had started smoking by the age of 16 compared with two of the 11 'healthiest' controls (Figure a). These differences were not seen between cases and 'average' controls (Figure 9b). In conclusion Tlco cases and 'healthiest' controls and FEVt cases and 'average' controls differed in the number of men smoking 25 or more cigarettes per day at weekends. A similar difference was found betw en Tlco cases at the PVC factory and the foundry. In general, cases started smoking at a younger age than controls. R&S 002617 .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 Tlco 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 cases were men with lowest gas transfer factor after allowing for age, height, weight and smoking habit. Men from a nearby foundry were included in the study in order to increase the number of men with low or no exposure to possible respiratory hazards at the PVC factory, but who were exposed to similar environmental conditions outside their workplace. In all 265 men from the PVC 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 valves. This ndicated that it was unlikely that a substantial number of men in the Ihole population were suffering from a clinically important reduction of he Tlco. In the case-concrol study the 51 men with the lowest Tlco after allowing for age, height, weight and smoking habit were selected as 'cases*. This does not imply that all 51 were suffering from lung disease, but among them were 15 men whose Tlco was less than 7C# of the value predict d by published normal values, a level 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 practic , and may possibly reflect pulmonary fibrosis or disturbances f the blood flow in the lungs. Th degre of r duction of transfer factor of carb n monoxide and associated airflow obstruction might have b en sufficient to cause breathlessness on exertion in som of these men. 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 were 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 made in this study. The PVC workers were slightly 07er-represented among the cases with low Tuco, 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, were 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 worked 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 b fore 1975 might have b en responsible for some impairm nt of the gas transfer factor in some of these men. The most obvious candidate for suspicion is VCM, exposures to which are known to have R&S 002619 J3 (/) 18 fl been much higher than post-1975 levels. Some support for this is o> N> provided by published case reports of VCK ^workers with impairment of gas transfer factor, but proof of association has been lacking though it is possible that many workers throughout the factory were exposed to a lesser degree. It is also possible that exposure to I respirable ?VC 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 transfer factor) and slighz chest radiographic abnormalities (NA3TRANGEL0 et al., 1979*, SCUTA3 et al., 19fic). There was no evidence to suggest that a current risk to respiratory H health exists at either the PVC factory or foundry. ^teSome differences m smoking habit were found between cases ana controls % tjnon-smokers being slightly commoner among controls, and heavier smokers ^slightly commoner among the cases. The cases tended to start smoking at a slightly younger age. We do not know if these small differences in smoking habit were sufficient to account for ths 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 (3950. If the men not examined had included either ar. 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 volum in one second, was carried out for the PVC workers only. While eora Imen did have impairment of this test result as would be expected in an industrial population of this kind, no associations with occupation could be d mcnstrated. R&S 002621 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 PVC factory or foundry employees* There was, however, a small number of men in both factories with impairment of their transfer factor. This could not be shown to be associated with current working conditions at either factory, but the pattern of results among PVC 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 seme 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, togither with a clinical assessment of the extent of lung damage in selected men. .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. R&S 002622 21 REFERENCES AGARWAL DK, KAW JL, SRIVASTAVA SP, SETH PK (1978) Some biochemical and histopathological changes induced by polyvinyl chloride dust in rat lung. Environmental Research; 16: 333 - 341. R&S 002623 ARNAUD A, PCMMIER de SANTI P, GARBE L, PAYAN H, CHARPTN J (1978) Polyvinyl chloride pneumoconiosis. Thorax; 33: 19 - 25. CHIVERS CP, LAWRSNCE-JONES C, PADDLE GK (1930) Lung function in workers exposed to polyvinyl chloride dust. British Journal of Industrial Medicine; 37: 1^7 - 151. COPDIER JM, FIEVEZ C, LEFEVRE M-T, SEVRIN A (1966) Acroosteolyse et lesions cutar.ees associees chez deux ouvriers affectees au nettoyage d'autoclaves. Cahier3 de Medecine du Travail; 4: 14 - 19- COTES JE (1979) Lung function. Oxford: Scientific Publications: 369 - 385. Blackwell CREECH JL, JOHNSON MN (1974) Angiosarcoma of liver in the manufacture of polyvinyl chloride. Journal of Occupational Medicine; 16: 150 - 1$1. DARKE CS (1976) Vinyl chloride and the production of PVC (Discussion). Proceedings of Royal Society of Medicine; 69: 280. FRONGIA N, SPINAZZOLA A, BUCARELLI A (1974) Lesioni polmonari sperimentali da inalazione prolungata di PVC in ambiente di lavoro. Medicina del Lavoro; 65: 321 - 342. GAMBLE J, LIU S, McMICHAEL AJ, VAXWEILER RJ (1976) Effect of occupational and nonoccupational 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. Revi w. In: Orie NGM. Van Der Lende R, ds. Bronchitis III. Proc edings of th Third International Symposium on Bronchitis at Groningen, The Neth rlands. 22 LANGE CE, jtfHE S, STEIN G, VELTMAN G (1973) Die sogenannte Vinylchlorid-Krankheit - eine berufsbedinjrte Systemsklerose? International Archives of Occupational Health; 32: 1 - 32. LILIS R, ANDERSON H, NICHOLSON WJ, DAUM S, FISCHBELN AS, SELIKOFF IJ (1975) Prevalence of disease among vinylchloride and polyvinyl chloride workers. Annals of New York Academy of Science; 246: 22 - 41. LILIS R, ANDERSON H, MILLER A, SELIKOFF IJ (1976) Pulmonary changes among vinyl chloride polymerisation workers. Chest; 69: (Suppl. 2 Feb.), 299 - 303. MASTRANGELO G, MANNC M, MARCER G, BARTCLUCCI GB, GEMIGNANI C, SALADINO G, SIMONATO L, SAIA B (1979) Polyvinyl chloride pneumoconiosis: epidemiological study of ex-posed 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 Pa"ty on Research into Chronic Bronchitis. Publications Group, Medical Research Council, 20 Park Crescent, London WIN 4AL. KILLER A, TEIRSTEIN AS, CHUANG M, SELIKOFF IJ (1975) Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride. Annals of New York Academy of Science; 245: 42 - 52. PRODAN L, SUCIU I, PISLARU V, ILEA E, PASOU L (1975) Experimental chronic poisoning with vinyl chloride (monochloroethane). Annals of New York Academy of Science; 245j 159 - 163- SOUTAR CAr COPLAND LH, THORNLEY PE, HURLEY JF, OTTERY J, ADAMS WGF, BENNETT B (I98O) Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust. Th rax; 35: 644 - 652. SICIU I, DREJMAN I, VELASKAI M (1967) Study of dis ase caused by vinyl chloride. Medicina d 1 Lavoro; 58: 261 - 271. R&S 002624 23. VELTMAN G, LANGE CE, JUHE S, STEIN G, BACHNER U (1975) Clinical manifestations and course of vinyl chloride disease. Annals of New York Academy of Science; 2U6: 6 - 17. VERTKIN YI, MAMONTOV YR (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 2 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 Management and office staff * These men are most likely to have been exposed to high concentrations of VCM in the past. These men are involved in the bagging of PVC and are probably exposed to higher concentrations of dust than other workers in the dryer buildings.*** *** These men are potentially exposed to all raw materials and products. R&S 002626 R&S 002627 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, slugman, ladle repairer, concrete liner. 2 Sand and blasting: coremaker, 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 mate, maintenance fitter, turner, trainee in the training centre, borer, saw repairer, wagon repairer, milling operator, inspector in machine shop, welder. ^ General and other: labourer, patternmaker, plater, platelayer, pipe loader, crane driver, driver, cleaner, technician, trainee, pipe roller, slinger, quality control, joiner, greaser, inspector, saddler, bricklayer, core inspector, despatcher, 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 TABLE 3 27 Featur s of Tuco cases, controls and total surv y population* Mean (and standard deviations) of age, height, weight and Tuco. Number of men Cases 31 Tuco Grouns Controls (average) 31 Controls (healthiest) 31 loida survey population 484 Age (yrs) Mean 41*8 (SB) (10.2) 42.3 (12.5) 40.3 (11.3) 42.2 (11.9) R&S 002628 Height (cms) Mean 176*1 (SB) (7.1) 174*0 (6.6) 173.9 (5.6) 173.8 (7.0) Weight (kgs) Mean 82.7 (SB) (13.3) ! Tlco Mean (ml/min* mm Hg) (SB) 22.2 (4*1) 34.9 (18.5) 31.8 (2.9) 79.2 (9.5) 37.3 (4.3) 30.2 (12.6) 30.5 (5.9) TABLE 4 28 Features of FE7t cases, controls and total survey population. Mean (and standard deviations) of age, height, weight, Tlco, FEVj and FVC. Number of men Cases 30 Tlco Groups Controls (average) 30 Controls (healthiest) 30 Total survey population 264 Age (yrs) Mean (31) 43.3 (11.0) 41.3 (12*5) Height (cms) Mean (SI) 1?6*0 (7*4) 174.5 (6.6) Weight (fcgs) Mean (SD) 82.2 (13.3) 78.4 (10.1) FE71 (litres) Mean (SB) 2.7 (0.7) 3.9 (C.7) FVC (litres) Mean (SD) 4.1 (0.9) 5.1 (0.8) Ti_co Mean (ml/min,.inmHg) (SD) 29.1* (6.8> 32.3 (6.0) 42.1 (12.0) 175.5 (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) S0.4 (12.3) 3-7 (0.9) 4.9 (1.0) 30.5** (6.1)** R&S 002629 * Value based on 29 observations. ** Value based on 262 observations. TABLE 5 / Age distribution of Tuco esses and controls and the total survey population by employment status* CASES PVC current men PVC leavers Foundrymen Age ranges in years 0-24 25 - 34 35 - 44 45 - 54 55 - 64 65+ 1 46 2221 1 1 434 AVERAGE CONTROLS PVC current men PVC leavers 1 413 1 12 Foundrymen 3 2544 HEALTHIEST CONTROLS PVC current men PVC leavers Foundrymen 2 3241 12 1 2643 TOTAL POPULATION PVC current men PVC leavers Foundrymen 009200 S9U 9 4 17 37 57 35 26 0 24 33 19 11 10 48 50 60 44 0 Total 11 8 12 9 4 18 12 3 16 164 101 219 TABLE 6 50 Employment status of Tuco cases, controls and total survey population. Number of men in each employment group with percentages- in brackets. Four men excluded, see text. PVC Current Workers PVC Leavers Foundry Total Total survey population 164 101 219 484 C&3G? Controls (average) Controls (healthiest) All 11 ( 3*0 8 ( 55) 12 ( 26) 9 ( 28) 4 ( 27) 18 ( 39) 12 ( 33) 3 C 20) 16 ( 35) 32 (100) 15 (100) 46 (100) 31 31 31 93 TABLE 7 Employment status of FEV^ cases, controls and total survey 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. PVC - Current Workers Total survey population 165 PVC Leavers 99 Total 264 Cases Controls (average) * Controls (healthiest) All 14 ( 26) 18 C 34) 21 C 40) v53 (100) 16 ( 43) 12 ( 32) 9 ( 24) 37 (100) 30 30 30 90 R&S 002631 TABLE! 8 Distribution of observed Tico an a percentage of predicted Tuco uaing Cotes's regression model for non-amokers. Numbers of men (percentages in brackets) for the oases, two control groups and total survey population. 4 **9 50 - 59 60 - 69 Tt-co % predicted 70 - 79 80 - 89 90 - 99 100 - 109 110 - 119 } 120 Total Cases Controls (average) Controls (healthiest) 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 H (45.2) 31 Total survey population 4 (0.8) 14 (2.9) 29 (6,0) 75 114 (15*5) (23,6) 120 (24.8) 82 (16.9) 46 484 (9,5) V/* 9200 SSfcj 809200 S9U TABLE 9 Distribution cf observed FEVj as a percentage of predicted FEV, using Cotes'a regression model for non-smokers* Numbers of men (percentages in brackets) for the cases, two control groups and total survey population. TABLE 10 Petails of the 10 PVC factory Ttco oases with the lowest standardized residual values of T!-co. Case No. 1 did not complete the spirometry task. Predicted values are for non-smokers (Cotea, 1979). No, Age Ranee Smoking category 1 30-34 0 SR Tlco Ti-eo TV co % FEtl^ litres TEVX litres Tev^ m (observed) (predicted) predicted (observed) (predicted) predicted litres m* i 2.89 2Q. 1 34,6 *8.3 - - --- 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 63.3 3.6 3.8 95.2 5.2 68.9 4 4o - 44 E - 2.15 20.9 30.5 68.4 1.2 3.5 34.3 3.5 35.1 5 35-39 0 - 2.11 20.8 6 55-59 C - 2.C2 14.7 32.1 23.9 64.6 61.4 3.2 2.6 3.8 84.9 4.1 77.9 2.7 95.5 3.3 77.9 1 50-5** a - 2.01 15.4 25.9 59.5 2.7 3.0 90.6 4.3 62.2 8 35 - 39 ' c - 1.99 23.3 35.5 65.6 4.2 4.1 101.7 5.7 74.3 9 45 - *9 N - 1.92 22.5 29.2 77.0 ` 4.1 3.4 120.1 5.1 80.0 10 50 - 54 C - 1.84 18.8 29.0 64.8 3.6 3.3* 107.9 4.7 75.8 Tbs abbreviations of smoking categories are as follows! 0 m current meeker E Ex-smoker Tuc units ere ml/ftia* ** 9 * life-long non-smoker 9Z00 S?U 34 TABLE 11 PVC factory Tuco cases and controls. Mean times (years) sp nt 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 had 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 CD 3.3 C5> 1.5 (1) Occupational groups 2 3i4 5 0.4 6.1 9.0 9.7 (5) (3) (4) (2) 0.8 11.8 (6) - - 1.1 6.8 7-1 12.3 (3) (D (4) CD 0.4 (4) - 1.8 CD - 1.2 10.8 7.3 3.3 (8) CD (2) (2) 0.5 (3) - - R&S 002635 TABLE 12 35 Foundry Tlco cas a 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 of men 1 Occupational groups 2 3 4 567 CASES 12 7.3 3*0 12.3 4.0 3.2 11.4 1.0 (4) (2) (5) (7) (2) (2) (1) AVERAGE CONTROLS 18 4.6 16.1 30.4 (3) (5) (D 9.4 (9) HEALTHIEST CONTROLS 16 13.4 C5) 4.5 (3) 12.7 (3) ' 12.5 (8) 7.4 10.6 2.5 (1) (5) (1) 11.6- (6) - __________ 1 TABLE 13 PVC factory FEVj cases and controls. Mean times (years) spent in each occupational group with number of men in brackets. See Table 1 for key to occupational groups. 30 ) o Number of men 1 CASES Current men Leavers 14 5-5 (7) 16 2.1 (8) AVERAGE CONTROLS Current men Leavers 18 3.2 (10) 12 1-3 . (5) HEALTHIEST CONTROLS Current men 21 6.4 Cio) Occupational groups 2 3 41 5 1.3 4.3 (8) (2) 0.8 4.7 (9) (3) 6.1 6.8 (6) (2) 1.0 - (2) 1.2 (10) 0.9 (7) 5-2 (1) 4.1 (3)- 7.6 7.7 (5) (2) - 1.2 - (3) 1.2 (10) 0.7 (2) 7.2 (9) i 3.6 (3) 6 3.8 (1) - 5.0 (2) 3-1 (2) 2.6 (2) R&S 002637 36. TABLE 14 For Tuco analysis, the distribution of numbers of FVC 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 2 10 Total 33 14 19 13 15 47 TABLE 15 PVC factory Tlco cases. Number of men within each age group and duration of pre-1975 employment category. Time of employment Duration of employment 0-24 25 - 34 Age (yxs) 35-44 45-54 55 - 64 65 + Total < 2 yr 1 341 9 Pre 1975 < 2 - 4 yr > 4 yr 12 4 3 15 P st 1975 - # 1 1 2 Total 1 2 6 8 1 1 19 37 TABLE 16 PVC factory Tlco average controls. Number of men within each age group and duration of pre-1975 employment category. Time of employment Duration of employment 0-24 25 - 34 Age Cyra) 35-44 45 - 54 55 - 64 65 + Total Pre 1975 Post 1975 Total < 2 yr J 2 - 4 yr > 4 yr - 112 21 1 12 11 2533 4 3 4 2 13 TABLE 17 PVC factory 'Q.co healthiest controls. Number of men within each age group and duration of pre-1975 employment category* Time of employment Duration of employment 0-24 25-34 Age (yrs) 35-44 45-54 55-64 *! roxai 65 + Pre 1975 f < 2 yr | 2 - 4 yr [ > 4 yr 1 1 1 11 2 4 0 a* Post 1975 - 2 32 3 10 Total 3 5241 15 33 e c/> oN> 0> W 00 R&S 002639 38, TABLE 18 For FEVt analysis, the distribution of numbers of PVC cases and controls who had worked at the PVC factory before 1975 and only after 1975* Pre 1975 Post 1975 Total Cases 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 15 46 TABLE 20 39 For T-co analysis, th 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 R&S 002640 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 Ehiulsion and suspension 8 7 10 25 Suspension only 18 U 13 44 Neither suspension nor emulsion 4 10 7 21 Total 3 30 30 90 TABLE 22 40 PVC factory Ttco cases and controls. Number of men who hav 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 7 0.9) 7 (10.1) 03 (9.6) 6 (6.9) 3 (6.1) 0 - 2 (17.4) Other 8 (11-5) 7 (10.4.) 8 '\(tr 'y R&S 002641 TABLE 23 PVC factory FEV. cases and controls. Number of men who hav 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 30 AVERAGE CONTROLS 30 HEALTHIEST CONTROLS 30 Steel Noxious occupations Chemicals Coal Other 10 (4*6) 5 (4.0) 16 (15.7) 16 (13.2) 7 (9.8) 6 (14.0) 9 (6.3) 15 (7.5) 4 (9.D 11 (13.6) 18 (8*9) * CD TABLE Zb 41 Foundry Tlco cases and controls. Humber of men who hav worked In noxious occupations with mean number 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 12 1 (3.0) 0 (0.0) 3; (5U) 5 (1.3) AVERAGE CONTROLS 18 2 (9.6) 0 (0.0) 4 (9.0) 8 (10.9) HEALTHIEST CONTROLS 16 2 (4*7) 0 (0.0) 5 (2.9) 5 (7.2) R&S 002642 TABLE 25 42. Smoking habits of Tuco cases, controls and total surrey population* Number of men in each smoking 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 TABLE 26 Smoking habits of FEVj cases, controls and total survey population. Number ox men in each smoking category with percentages in brackets. Cases Controls (average) Controls (healthiest) Total surveypopulation NonSmoker 5 (18.7) Current Smoker 13 (43.3) 7 (23.3) 15 (50.0) 9 (30.0) 12 (40.0) 59 (22.3) 125 (47.4) S-StaK>ker Total 12 (40.0) 30 8 (26.7) 30 9 (30.0) 30 80 (30.3) 264 R&S 002643 Number of men *0. R&S 002644 m to w 01 o> o cji ^ co to o R&S 002645 45. Fig. 3 Number of cigarettes smoked or weekdays by FEV^ cases and 'healthiest' controls who are current smokers. Fig. 4 Number of cigarettes smoked on weekdays by Tlco cases and 'healthiest' controls, at the Number of men ^7. h-* NS W rfi. U1 O l ~3a> W U M M R&S 002646 Fig. 5 Number of cigarettes smoked per day at weekends by Tico cases and 'healthiest' controls, at the PVC factory and the foundry, who are current smokers. 49. 8- 7- 6- 5- sOG 43- o 2- 1- 03 JO 3 2: XU 4+1 2 2 10 20 30 40 50+ 2 ap --L-l PVC factory Foundry Cases No. of cigs. 'Healthiest' controls. - Fig. 6 Maximum number of cigarettes regularly smoked per day by lYco cases and 'healthiest' controls, at the PVC factory and the foundry, who are current smokers. Number of men R&S 002647 Fig. 7 Maximum number of cigarettes regularly smoked per day by FEV1 cases and 'healthiest' controls. 51 (a) (b) Num ber of men R&S 002648 Fig. 8 a) Age when started smoking cigarettes, for T<. co cases and 'healthiest* controls at the PVC factory and the foundry, who are current smokers. b) Age when started smoking cigarettes, for TlCo cases and 'average* controls, who are current smokers. (a) (b) 0 PVC factory Cases 0 <141617181920 2L+ Age(yrs) 'Average' controls Fig. 9 a) Age when started smoking cigarettes, for FEV. cases and 'healthiest' controls, who are current smokers. b) Age when started smoking cigarettes, for FEV- cases and 'average' controls, who are current smokers. R&S 002649 53 APPENDIX 1 SMOKING QUESTIONNAIRE 1 Do you smoke? If NO la Have you ever smoked as much as one cigarette a day (or one cigar a week or an ounce of tobacco a month) for as long as a year? If NO to both parts of question 1, emit remaining questions on smoking. 2 How old were you when you started smoking regularly? 3 How old are you now? 4 Do (did) you smoke manufactured cigarettes? If YES 4a How many do (did) you usually smoke 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 smoked regularly per day? 4d For how long were you smoking that many? 4e Since starting smoking tobacco have there been periods during which you did not smoke cigarettes? If YES, for how long altogether were you not smoking cigarettes? 4f (Apart from those times) what was the least number of cigarettes you ever smoked regularly per day? 4g For bow long were you smoking that many? 5 Do (did) you smoke hand-rolled cigarettes? If YES 5a How much t bacco do (did) you usually am ke per week in this way? R&S 002650 APPENDIX 1, page 2 5*. 6 Do (did) you smoke a pip ? If YES 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 8a How many of these do (did) you usually smoke per week? For ex-smokers: 9 When did you last give up smoking? l * R&S 002651 55- APPENDIX 2 NOXIOUS 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 Wocd cutter/sawmill worker Construction worker Bricklayer Plasterer Quarryman Paper Bill worker Electrician Joiner Glassworker Welder Scrap burner Foreman Coking plant worker Furnace operator Car body reoairer Paint sprayer . Painter/decorator Tarmacadam exposed workers 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 T.co and age* height and weight and between FEVt 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 Tuco analysis, this was a significant improvement in the amount of variation explained* However, this 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 Tt-co (but not the FEVj model) was further improved by introducing different intercepts and age slopes for three categories of smoking, non-smokers, current smokers and ex-smokers. This analysis 3howed that for ex-smokers the mean valuv of Tlco was significantly higher thaii that of current smokers (P < 0.05) but that they experienced, a greater loss of Tlco with age than current and non-smoker3 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 former 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 leav rs from the PVC factory who were current smokers was significantly lower (P < 0.1) .than 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. Henc the model used was the one in which different intercepts and age slopes wer allowed for the three smoking groups. For reasons of consist ncy the FEVj analysis was als based on this same m del although there was no significant improvement in the amount of variation explained as there had been f r the Tlco analysis. The results for FEVj analysis show that there was a significant difference (P < 0.1) in the rate of loss of FfiV^ with age between non-smokers and current R&S 002652 APPENDIX 3, page 2 TABLE 1 57. Regression for Tt_co (ml/min. mm Hg) allowing dlff rent intercepts and age slopes for three smoking groups. Variables Age Height Weight Units Tears cm kff Mean 42.2 173.8 80.2 Constant for non-smokers Regression coefficient -0.2246 0.1552 0.0572 Constants (intercents) 10.3052 t -5-74 4.74 3.23 - P < 0.001 < 0.001 < 0.002 Effect on intercept of: Current smokers Ex- smokers Effect on age slope fort Current smokers Ex-smokers -2.5288 t.4554 -1.34 0.69 NS NS - -0.0154 -0.0537 -0.33 -1.08 NS NS . R&S 002653 TABLE 2 Regression for FE7t () allowing different intercepts and age slopes for three smoking groups* Variables Units Mean Age Height Weight Tears cm kg 42.2 174.3 80.4 -. Constant for non-smokers Effect on intercept oft Current smokers Ex-smokers Regression coefficient -0.0309 0.0420 ' 0.0003 t -4.55 7.13 0.09 Constants (intercepts) -2.1725 0.4209 0.2675 1.24 0.75 Effect on age slope fori Current smokers Ex-smokers .-0.0149 -n. <viq< -1.81 _1.il P' < 0.001 < 0.001 NS NS NS < 0.10