Document 2RLZxxZ88wQobROZagJeZ3q36

British Journal of Industrial Medicine 1991;48:275-278 275 Diurnal variation in peak expiratory flow rate among polyvinylchloride compounding workers H S Lee, T P Ng, Y L Ng, W H Phoon Abstract The diurnal variation in peak expiratory flow rate (PEFR) was studied in 24 mixers and 24 non-mixers in three polyvinylchloride (PVC) aim was to determine whether PVC compounding workers have increased diurnal variation in PEFR suggesting exposure to a potential bronchoactive agent. compounding plants and 24 non-PVC controls from a marine police workshop. The three Materials and Methods groups (all men) were matched for age, race, MANUFACTURING PROCESS and smoking. The mean respirable dust The study was conducted in three PVC compound concentration (essentially PVC dust) was ing factories. Polyvinylchloride pellets were 16 mg/m1 for mixers and 0*4 mg/m3 for non produced by mixing together PVC resin powder with mixers. The mean diurnal variation in PEFR other additives such as plasticisers (for example of the mixers was 6*5%. This was significantly di-octylphthalace), stabilisers (for example, lead higher than the 4*8% for non-mixers and 4*3% sulphate), fillers (for example, calcium carbonate), for the non-PVC controls. Six mixers had a and pigments. Azodicarbonamide (a blowing agent) diurnal variation of more than 15% on at least was not used in the three factories. The bulk of the one day compared with none among the other raw material was die PVC resin powder constituting two groups. Twenty nine per cent of mixers more than 90% by weight of the mixture. The complained of wheezing compared with 4% of mixture was then blended and heated up to 170*C non-mixers and none among non-PVC work and extruded as pellets. ers. These differences were significant. Forced The most visibly dusty job was that of the mixers expiratory volume in one second (FEV,) for the who had to open bags of dry powdered materials and mixers was 10% below the predicted values whereas that of non-PVC workers was 2% below predicted values. The study indicates a significant acute airway constriction from occupational exposure to PVC dust. tip them into hoppers. This was carried out on raised platforms (about 8-10 m high). Temperatures in the hoppers were around 135*C, the result of frictional heat from blending. The hoppers were equipped with local exhaust ventilation. Heating and extrusion took place at the floor level. A case of occupational asthma due to unheated polyvinylchloride (PVC) resin dust has been re ported recently.1 Both obstructive and restrictive The extruded pellets were collected and packed by the packers who were exposed to a relatively low level of dust. Other less exposed workers were forklift drivers, storemen, mechanics, fitters, electricians, ventilatory impairment and a high prevalence of material testers, cleaners etc. wheezing complaints have been reported among PVC fabrication workers.31 Abnormalities of lung STUDY POPULATION function have also been reported in surveys of other A total of72 male workers were studied, consisting of workers exposed to PVC dust.45 24 mixers, 24 low exposure non-mixers, and 24 non- We studied the diurnal variation in the peak PVC controls. All mixers in the three factories were expiratory flow rate (PEFR) in a group of PVC invited to participate in the study. The 24 mixers compounding workers and in a control group. Our represent 80% of all mixers. The low exposure PVC workers and the non-PVC controls were matched Department of Industrial Health, Ministry of Labour, MOL Building, 18 Havelock Road, Singa pore 0105 H S Lee, W H Phoon with the mixers for age (five years), race, and smoking state. The low exposure PVC workers were for example, forklift drivers, storemen, maintenance staff, and material testers from the same three PVC Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore T P Ng, Y L Ng factories. The non-PVC controls were mechanics and maintenance stafffrom a marine police workshop with no exposure to PVC dust or any known asthma inducing agents. 22530001 BFG21380 276 Lee, Ng, Ng, Phoott PEFR RECORDING Each participant was given a mini-Wright peak flow meter and instructed in its correct use. He was asked to perform three blows after maximal inspiration on each occasion and to record the results on a form. The highest of the three readings was taken. Six daily recordings (every three hours) during the waking hours were made for one week (six working days and one day off). Recording started on a Monday and were made both at the workplace and at home. The diurnal variation in PEFR was calculated as the difference between the highest and lowest PEFR values as a percentage of the highest PEFR on each day. For each worker the mean diurnal variation for the one week period was calculated. sampling. Analysis was by liquid chromatography for HCI and by gas chromatography for VCM. STATISTICAL ANALYSIS Statistical methods to compare exposed workers and controls were analysis of variance (F test), t test for independent quantitative variables, / test, and Fisher's exact test. Results ENVIRONMENTAL ASSESSMENT Respirable dust concentrations for mixers (21 sam ples) ranged from 0 2 to 2 9 mg/m} with a mean of 1-6 mg/m1. Respirable dust concentration for non PULMONARY FUNCTION Forced expiratory volume in one second (FEV,) and forced vital capacity (FVC) were performed on a dry wedge spirometer (Vitalograph) on Monday morn ings when workers began their shifts. The spirometer was calibrated before use. The best FEV, and best FVC were taken from three technically satisfactory forced expiratory manoeuvres where the best two recordings were within 5% of each other. All values were corrected to body temperature and pressure saturation. Height (to the nearest centimetre) was measured without shoes. Predicted normal values for FEV, and FVC were calculated based on regression equations developed by Zee6 for local Chinese and mixers (24 samples) ranged from 0-1 to 1-0 mg/m1 with a mean of 0*4 mg/m*. Hydrogen chloride and VCM were not detected in any of the eight samples taken (detection limit -- 0-03 mg/m* for both HCI and VCM). STUDY POPULATION Among the 72 subjects, 33-3% were Malays and the rest Chinese. Fifty four per cent were smokers (including 17% ex-smokers). Tables 1-3 summarise personal data, prevalence of respiratory symptoms, and results of lung function tests and PEFR monitor ing of these subjects. Non-PVC subjects were taller than those in the other groups. Although they Malay men. Table 1 Characteristics of study population RESPIRATORY QUESTIONNAIRE Each subject was interviewed by a trained field investigator using a structured questionnaire. Data were obtained on pulmonary symptoms, personal biodata, detailed work history including previous employment, past medical history, atopy, and smok ing habits. ENVIRONMENTAL ASSESSMENT A total of 45 personal breathing zone samples of respirable PVC dust were collected over two to four hours on cellulose ester membrane filters of 37 mm diameter and 8*0 /an pore size using SKC personal dust sampling equipment at flow rates of 2 0 1/minute. Twenty one samples were taken from mixers and 24 samples from less exposed workers (non-mixers). A total of eight static samples of air were collected for analysis of hydrogen chloride (HC1) and vinyl chloride monomer (VCM) (four each). Sampling was taken from four points: one near the mixer (on the platform), two near the extruder (floor level), and one outside the factory (ambient air). Sampling duration High exposure mixers In m 24/ Lena exposure 'ton-mixers >n 24/ Age 38 0 (8-4) Exposure duration to PVC (y) IM (5-7) Height (cm) 165 8(5-8) Cigarette-years 150-1(258-0) FEV, (1) 2-8 (0-5) FVC (I) 3 2 (<P6) 36-8 (8-1) 13-0(5-8) 166-0 (7 0) 165-2 (208-7) 3-0 (0-6) 3-4 (0-7) Data are given as mean (SD). *p < 0 05 (ANOVA). Table 2 Prevalence of symptoms Cough Phlegm Rhinitis Eye irritation Breathlessness Wheeze High exposure mixers in = 24) Low exposure non-mixers In = 24) 4(16-7) 6(25-0) 5(20-8) 4(16-7) 3(12-5) 7(29-2)' 2(8-3) 4(16-7) 7 (29-2) 1 (4-2) 2 (83) 1 (4-2) Non-PVC corkers > n - 241 36-3(8-1) -- 170-5 (5-7)* 186-7 (281 1) 3-3 (0-5) 3-7 (0-6) Non-PVC workers In ~ 24) 2(8-3) 1 (4-2) 5 (20-8) 1 (4-2) 1 (4-2) 0(0) was three hours. For HC1 sampling, air was drawn through an impinger at 1 1/min. Air was drawn through a charcoal tube at 80 ml/min for VCM Dau are given as number (%) with positive symptoms. *p = 0-002 (f test); p => 0005 compared with non-PVC controls (Fisher's test); p = 0-02 compared with low exposure non-mixers (Fisher's test). 22530002 BFG21381 Diurnal variation in peak expiratory flow rate among polyvinylchloride compounding workers 277 Table 3 Results of lungfunction and PEFR High exposure mixers <n - 24) Lems exposure non-mixers in - 24/ Non-PVC workers in * 24) n<i Predicted FEV, % Predicted FVC FEV, FVC(%j DV PEFR 90-4(10-8)* 90-9(12-5) 86-5(6-1) ft 5 (4 2)* 94-2 (13-7) 93-4(12-6) 87 f (4 6) 4 8(2 3} 97-6(10-9) 96-9(10-9) 87-4(5-6) 4-3(2-3) Data arc given as mean ; SD). *p = 0-03 compared with non-PVC controls (/ test). "p -- 0 03 compared with non-PVC controls (r test); p = 0 05 compared with low exposure non-mixers (t test). smoked more, this was not statistically significant (table 1). More mixers complained of wheeze than did other subjects. No significant difference was found in the prevalence of other symptoms (table 2). The FEV, of the mixers was 10% below the predic ted values whereas that of the non-PVC subjects was 2% below the predicted values (p = 0-03). The mean diurnal variation in PEFR of the mixers of 6-5% was higher than either of the other control groups (table 3). Six mixers had a diurnal variation of greater than 15% on at least one day compared with none among the other groups (p = 0 01, Fisher's test). The highest diurnal variation in a day was 23-9% in a mixer. Discussion Diurnal variation has been studied in workers exposed to grain dust7 and tobacco dust.8 It has been shown that age and smoking were significantly correlated in a positive fashion with diurnal variation in PEFR. The mixers in our study had a higher diurnal variation in their PEFR compared with both low exposure and non-PVC controls matched for age, smoking state, and race. The diurnal variation in PEFR among PVC work ers has not been investigated in any previous study. The median diurnal variation in PEFR of grain elevator workers was 5-9%.' This is slightly higher than the median diurnal variation in PEFR of 4-8% for PVC mixers. The method for calculating diurnal variation in PEFR, however, for the grain elevator workers was different and resulted in a higher diurnal variation. The diurnal variation in PEFR was cal culated as the difference between the highest and lowest PEFR values as a percentage of the mean PEFR on each day. In our case we expressed the difference as a percentage of the maximum PEFR on each day. Furthermore, the grain elevator workers were older (median age = 44 years) and had higher prevalence of smoking (81% were smokers). The mean diurnal variation in PEFR in a group of tobacco workers was 14-4% and for their controls, it was 9-5%.* This is much higher than that seen in our subjects although method of calculating diurnal variation in PEFR was similar to ours. Their subjects were mainly women, however, and older (mean age = 43 years). The prevalence of smoking was 43-8%. Also only four PEFR recordings were taken each day. The higher prevalence ofwheezing complaints and reduced FEV, (below predicted values) among mix ers compared with non-PVC controls provide fur ther evidence that mixers in the PVC compounding industry may be exposed to a bronchoactive agent. We did not detect any overt cases of occupational asthma. This is however, not unexpected in a cross sectional study since we are likely to be studying a survivor population. We have recently completed a similar study of polyurethane foam operators exposed to toluene diisocyanate (TDI) (not yet published). No overt cases of occupational asthma were detected in this group of workers exposed to a known asthma inducing agent, TDI. Possible asthma inducing agents in the PVC compounding industry include PVC dust, additives, and PVC decomposition products (for example HC1, VCM). Among the additives, only azodicarbonamide is known to cause asthma but azodicarbonamide was not used in the three plants surveyed. So far dioctylphthalate (DOP) and other phthalate esters have not been identified as asthma inducing.10 Furthermore, the DOP was in liquid form. Other additives such as stabilisers (for example, lead, barium, cadmium, and zinc salts) are not likely to cause asthma. Polyvinyl chloride is thermally stable at temperatures below 225'C." Above 225'C, PVC will degrade, releasing first HC1 and then, above 300'C, carbon monoxide, carbon dioxide, benzene, and VCM. Above 600*C small amounts of phosgene and chlorine are formed. Under normal operating conditions, temperatures do not exceed 170*C. At the mixing station, tem peratures do not exceed 135*C. Hydrogen chloride and VCM were not detected in the vicinity of the mixer or the extruder. The bulk of the dust is PVC. That unheated PVC dust can induce asthma been shown by a positive challenge test.1 Our study provides further evidence -- of a significant effect of variable acute airway con striction from exposure to PVC dust. 1 Lee HS, Yap J, Wang YT, Lee CS, Tan KT, Poh SC Occupational asthma due to unheated polyvinylchloride resin dust. Sr J Ind Med 1989;46:820-2. 2 Ernst P, De Guire L, Armstrong B, Theriault G. Obstructive and restrictive ventilatory impairment in polyvinylchloride fabrication workers. Am J Ind Med 1988;14:273-9. 3 Baser M, Tockman MS, Kennedy TP. Pulmonary function and respiratory symptoms in polyvinylchloride fabrication workers. Am Rev Retptr Dii 1985;131:203-8. 4 Soutar CA, Copland LH, Thomley PE, Ottcry J, Adams WGF, Bennct B. Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust. Thorax 198035:644-52. 5 Soutar CA, Gould S. Clinical studies of workers exposed to polyvinylchloride dust. Thorax 198338:834-9. 6 Zee KO. Ventilatory function in normal industrial workers in 22530003 BFG21382 278 Lee, Ng,Ng, Pfuxm Singapore. Proceeding! of the XII Singapore-Malaysia Con gress of Medicine, the Academy of Medicine, Singapore, 1977:587-95. 7 Revsbech P, Anderson G. Diurnal variation in peak expiratory flow rate among grain elevator workers. Br J Ind Med 1989;46:566-9. 8 Lander F, Gravesen S. Respiratory disorders among tobacco workers. Br J Ind Med 1988;45:500-2. 9 Slovak AJM. Occupational asthma caused by a plastics blowing agent, azodicarbonaraide. Thorax 1981;36:906-9. 10 Nielsen J, Akesson B, Skerfving S. Phthalate ester exposure. Air levels and health ofworkers processing polyvinylchloride. Am Ind Hyg Assoc J 1985;46:643-7. 11 Froneberg B, Johnson PL, Zandrigan P). Respiratory illness caused by overheating of polyvinylchloride. Br J Ind Med 1982;39:239-43. Accepted I October 1990 I Vancouver style All manuscripts submitted to the Br J Ind Med should conform to the uniform requirements for manuscripts submitted to biomedical journals (known as the Vancouver style). The Br J Ind Med, together with many other international biomedical journals, has agreed to accept articles prepared in accordance with the Vancouver style. The style (described in full in Br Med J, 24 February 1979, p 532) is intended to standardise requirements for authors. References should be numbered consecutively in the order in which they are first mentioned in the text by Arabic numerals above the line on each occasion the reference is cited (Manson1 confirmed other reports2-1...). In future references to papers submitted to the Br J Ind Med should include: the names of all authors if there are six or less or, if there are more, che first three followed by et at; the title of journal articles or book chapters; the titles of journals abbreviated according to the style of Index Medieus; andthefirst and final page numbers of the article or chapter. Examples ofcommon forms of references are: 1 International Steering Committee of Medical Editors. Uniform requirements for manuscripts submitted to biomedical journals. Br Med J 1979;1:532-5. 2 Soter NA, Wasserman SI, Austen KF. Cold urticaria: release into the circulation of histamine and eosino-phil chemotactic factor of anaphylaxis during cold challenge. N Engl J Med 1976;244:687-90. 3 Weinstein L, Swartz MN. Pathogenic properties ofinvading micro-organisms. In: Sodeman WA Jr, Sodeman WA, eds. Pathologicphysiology: mechanisms ofdisease. Philadel phia: W B Saunders, 1974:457--72. 22530004 BFG21383 Scand J Work Environ lleaith 1991:17:53--') Pulmonary effects of polyvinyl chloride dust exposure on compounding workers by Tze Pin Ng, FACOM,1 Hock Siang Lee, MSc(OM,)2 Yong Meng Low, FRCR.3 Wai Hoong Phoon, FFOM,2 Yuen Ling Ng, Dip(FCT)' NG TP. LEE HS. LOW YM. PHOON WH. NG YL. Pulmonary effects of polvvinyi chloride dun exposure on compounding workers. Scand J Work Environ Health 1991 :U;53--9[*|piromeiry, chest radi ography, environmcmaJ measurements, and a questionnaire on respiratory symptoms were used 10 evalu ate the effects of exposure to polyvinyl chloride (PVC) dust on l?j Chinese and Malay PVC compound ing workers in comparison with an unexposed reference group. Workers with high cumulative PVC dust exposure had a lower forced expiratory volume in I s and forced vital capacity, and a higher prevalence of radiological profusion of small opacities. Wheezing or chest tightness was also significantly more fre quent in this group. Unlike previous studies, the PVC compounding workers in this study were exposed to only negligible amounts, if any. of vinyl chloride monomer or thermal degradation products of PVC such as hydrogen chloride, phosgene, or chlorine. The conclusion was^rawn that a low grade of pneu moconiosis and a small degree of lung function impairment is associated with PVC dust exposure. Re versible airways obstruction U aiso likely and warrants further investigation^ Key terms; radiological profusion, spirometry, symptoms. In 1970, Szende ci al (1) first described radiological and histopathoiogical evidence of a moderately diffuse fibrosis with granulomatous reaction in a worker ex posed to PVC dust. Since then, several epidemiologic studies have investigated the pulmonary effects of oc cupational exposure to vinyl chloride monomer (VCM) and poiyvinyl chloride (PVC). These studies have shown an increased prevalence of radiological, lung function, or subjective abnormalities (2--9). It would appear, however, that, in many of the earlier studies, control of possible biases or confounding was less than adequate because of the lack of appropriate reference groups, failure to take into account the influences of age or cigarette smoking properly, or the absence of standardized procedures in radiographic reading such as the use of standard radiographs of the International Labour Office (1LO) or multiple readers blind to the exposure status of the subjects. Several studies have also provided conflicting evidence for lung function impairment (4, 6, 7). it is also difficult to be certain that the pulmonary abnormalities reported in these studies were entirely due to exposure to PVC dust alone, since combined exposures to VCM and other air contaminants were known to be present. Most previous studies have in vestigated only vinyl chloride polymerization workers, who were exposed to both PVC dust and VCM (2--6). 1 Department of Community, Occupational and Family Medicine, National University of Singapore. 2 Industrial Health Department, Ministry of Labour, Singa pore. 1 Singapore Anti-Tuberculosis Association. Reprint requests to: Dr Ng Tze Pin. Department of Com munity, Occupational and Family Medicine. National Univer sity of Singapore, Lower Kent Ridge. Singapore 0511. VCM has been reported to cause pulmonary fibrosis in animals (10), and PVC dust exposure among work ers has been shown to induce less severe respiratory abnormalities than combined exposure to PVC and VCM (3). PVC fabrication workers have also been studied (7--9). but these included other process workers, such as in calendering, laminating, or extruding, with poten tial exposure to thermal degradation products, sol vents. and possibly additives known to cause acute bronchial reaction. No previous investigation has studied a group of workers exposed almost exclusively to PVC dust. We have conducted a study of one such group, namely, PVC compounding workers, and present the results of the radioiogical, lung function, and symptoms evaluation in this report. Materials and methods Manufacturing processes The study was conducted in three factories which produced PVC pellets which were then supplied to user industries for fabrication into other PVC products. The manufacturing processes were similar in all the fac tories, and no other processes were in operation ex cept in one factory, where the pellets were fabricated into PVC rails in a separate building 100 m away. The bulk of the raw material, constituting more than 90 % by weight, was PVC resin powder, which was com pounded with other chemicals such as plasticizers, stabilizers, and pigments in semiautomaied processes at temperatures not exceeding J70C, The most visi bly dusty jobs in the factories were performed by 22531001 BFG21384 mixers, who opened bags of the dry powdered mate* rials and tipped them into hoppers. Other workers with less PVC dust exposure were employed as packers/ weighers, forklift drivers, sioragemen, machine oper ators, fitters, electna'am, material testers, deancrs, and so forth (table 1). Environmental assessment Current personal exposure to respirable PVC dust was measured for 10 job titles in each factory. A total of 56 personal samples of respirable PVC dust from the breathing zone of the workers was collected over sam pling periods of about 4 h at the same time of the day on cellulose ester membrane filters with a diameter of 37 mm and a pore size of 8.0 pm. Personal dust sam pling equipment (SKC Inc) was used at a flow rate of 2.01/min. The job-specific exposures are summarized in table 1. Table 1. Oust coneenirauons in the three PVC factories by job title. JOB till* Miiara Foramen Clean** PeeKara ForfcUft ocaratota Storageman Mtcriin* ocaritota Macnamcatfettctncai titter* Malarial tatting wataara Scramranlng wemtra Niimoar o* Mian sampitt imgiml 21 159 3 a*2 I 0.72 9 0.28 6 0.*S 3 033 2 0.7 3 0.44 4 * 0.20 0.33 Range tmg/irHI 0.21-2.90 058--0.70 0.16--058 0.10-1.02 0.07-053 057--058 0.09-0.6$ 0.12--051 0.08--0.81 Freouency an ---------------------------------------------------------------------------------------- - -0 -3 - -9 -18 -15 -18 -21 -24 -27 -30 Mg/m3 - Yr Figure 1. Distribution of cumulative dust exposure. 54 Study populations All of the eligible 17! Chinese and Malay male work ers aged 21 years and above and currently employed in production and maintenance work in these factories were studied. Since almost all of the workers were ex posed to some degree of PVC dust, an external com parison group of unexposed workers was also studied at the same time. These were Chinese and Malay male workers, aged 21 years and above, with equivalent job titles such as drivers, mechanical workshop workers, electricians, and plumbers in three granite quarries (27 workers, 100 ^ response) and in one hospital (21 workers, 87 response). The comparison workers in the quarries were exposed to low levels of silica (aver age 0.1S mg/m3 respirable granite dust). A structured questionnaire was administered by trained field investigators to each worker, who pro vided his personal data, a detailed work history (in cluding previous employment in other dusty occupa tions), information on previous medical history of tuberculosis, hypertensive heart diseases and so forth, smoking habits, and responses to the British Medical Research Council questionnaire on chronic bronchitis* as well as to additional questions on wheezing or chest lightness and atopy. Spirometric testing was performed on a dry-wedged bellows spirometer (Viulograph2), which was regu larly calibrated before use, on Monday mornings when workers began their shifts after a weekend off. Each subject performed maximal forced expiratory maneu vers in the standing position without a nose clip, and the best of three acceptable curves was used in deriving the forced viral capacity (FVQ, forced expiratory vol ume in 1 s (FEYtfl), and the FEV [(lOOxFEVt>0)/ FVQ. All of the values were corrected to body tem perature and pressure saturation (BTPS). Height (to the nearest centimeter) and weight (to the nearest gram) was measured, the subject being without shoes and in light summer clothing. Chest radiography was performed on the entire group of mixers (who were the most highly exposed to PVC dust) and subsamples of exposed nonmixers and unexposed referents. Since the mixers were a gener ally older group, the exposed nonmixers included other production and maintenance workers except those in the PVC railing and screw departments, who were mostly young workers. The external comparison group included only workers in the quarry, who were also comparable in age to the mixers. Posiero-anterior radi ographs of the chest were taken on high-quality largesized film and were then read independently and in ran dom order by three readers, who were not aware of the exposure status ofthe subjects to which the radio graphs belonged. The profusion of rounded and irregu lar small opacities was read, with reference to stan dard films, and according to the 1LO International Standard Classification of Radiographs of Pneu moconiosis of 1980. There was reasonably good readcj ing agreement between the observers (appendix). Ki UT CO po BFG21385 Analyses Since the observed respiratory effects were almost cer tainly the results of cumulative pVC dust exposure. which is a function of exposure intensity and duration, a cumulative dust exposure index was estimated for each PVC-exposed worker on the basis of information provided on the duration of employment for every job ever held in the factories. The current factory- and jobspecific dust concentration was assigned to each job held and multiplied by the duration in years and cal culated as follows: C-OVT,. where C = the cumulative exposure index. K = the mean dust concentration (mg/m3), T=exposure duration (years), and jjob category. It was recognized, how ever, that current measurements could not be assumed to reflect the previous dust exposure intensities ac curately. Hence, the cumulative indices were only used to categorizeWorkers into high and low cumulative ex posure groups. This classification was done with the use of an arbitrary level of 10 mg/mj-years to sepa rate those with high cumulative exposure from those with low (or average) exposure. Typically, chose with a cumulative index higher than 10 mg/m3-years would represent a mixer exposed to an average PVC dust concentration of 1.0 mg/m3 for 10 or more years. The inclusion of, say, a packer typically exposed to 0.33 mg/mJ for 30 or more years was also allowed for. The distribution of the cumulative PVC dust ex posure indices is shown in figure 1. The unexposed group was assigned a nil cumulative exposure to PVC dust. Comparisons of the lung function parameters be tween the exposed groups were performed by multi ple regression techniques using general linear regres sion modeling procedures from the 5AS (statistical analysis system) programs. The FEV; o, FVC, and FEV w* were adjusted for age, height, cigarette-years, and race, entered as covariates in the models. The lung function parameters of the exposed groups were com pared with those of the unexposed group with sig nificance testing by an analysts of covariance. In ad dition, the lung function parameters of all the groups were compared with external population norms with the use of prediction equations for Singapore Chinese and Malay males (II, 12). Radiological opacities were defined categorically as a profusion of small opacities of O/l or greater. J/0 or greater, or 1/1 or greater, as read by two or more of the three readers. Separate analyses of the preva lence of radiological opacities for each reader were also performed. Stratified analyses and the Cochran-Manlei-Haenszel test were used when the prevalences of radiological opacities were compared, and also when the prevalences of symptoms were compared by ex posure groups with control for the influence of age (<45 years. a4S years) and smoking status (nonsmoker and ever smoker). Thirteen workers with significant dust exposure from other previous occupations, one worker with previous pulmonary tuberculosis, one worker with hypertensive heart disease, and one worker with current respiratory tram infection were excluded from the analysis. Results Table 2 shows the mean age. height, and the propor tions of each ethnic group and smokers by exposure group and table 3 the exposure characteristics of the groups. Multiple regression modeling showed both the FEV,.0 and FVC to be significantly related, in ex pected fashions, to age (PcO.OOI), height (PcC.ODtfl), and cigarette-years (P<0.01). Race was not a signifi cant independent variable after adjustment for smok ing in the model. FEV, 0 and FVC, after adjustment for the effects of these influencing variables, were both lower in the PVC-exposed groups (table **). The per centage of predicted FEV, 0 and FVC in the unexr posed group indicates that their lung volumes were comparable to the external population norms, where as both FEV, o and FVC were about 4 *# lower in the low-exposure group and 7 "is lower in the high-exposure group. The prevalence of respiratory symptoms among the exposure groups, after control forage and smoking, did not show any statistically significant differences except for frequencies of wheezing or chest tightness, which was greatest in the high-exposure group (table j). Radiological small opacities, as read by at least two readers, with profusion 0/1 and greater, age and smok ing being controlled for. were significantly more fre quent in the exposed groups in comparison with the Table Z Physical and smoking characteristics ot the subjects by cumulative exposure group. Group Hign exposure (N r34) Age years Mean SO Heigni term Mean SO 36.0 12.7 3SJ ?0.l 41# S.77 167.1 S.6 167.1 6J 165.4 S3 Race Chinese NH 39 SI 102 64 24 71 Malay NH 9 T9 19 16 10 29 Nonsmoker N * 1 33 63 52 10 29 Smoking gl Current amour smoaer N% N fk 48 6S 9 23 28 SB * < tO rogrm'ytars. * i 10 fflgrm'-yters. Cigaretteyears Mean so 239 377 55 22531003 BFG21386 Table 3. exposure characteristics of (he subjects by cumuletrve exposure firoup. (PVC = poiywnyi cnionde) Group Unexposed Low exoosure < < 10 mgmt'-vears) High exposure (%10 eng/m'-years) PVC cumulative exposure Mean _, 2.9 TS.O SO 2.6 5.5 Years exposee to PVC Mean SO 75 14.7 6.2 4.2 Mixers N% Job Exposed nonmixers N /. 9 74 30 12 112 92.6 4 114 Table 4. Lung functions by exoosure group. |FEV, 0 a forced expiratory volume in 1 s. FVC s forced vital capacity, FEV'/* (100 FEV, yPVCJ Group Unexposed Low exposure (< 10 mg/m'-years) High exoosure | a tp mg/m'years) FEV, g (l)* Mean SO 3.13 0.41 3.03 0.44 2.93 0.41 FVC (1)* FEV,, FVC (5% of predicted)* (% of predicted)* FEV%S Mean SD Mean SO Mean SO Mean SO 3.64 0.46 99.3 124 99.4 3,<7 0.53 96.4 12.3 95-1 3.39 0.47* * 92.7 12.4" 92.3 114 865 6.2 n.9 87.4 64 12.0-* 664 6.3 * Adjusted for age. height, race, cigarette-years. 6 Adjusted for eigareiie-yesrs. * P<0.05. `" ?<0.0l (analysis of covariance). Table 5. Respiratory symptom prevalence by exposure grouo. Symptom Unexposed N */ Low exposure (<i0 mg/m'-years) N High exposure I a 10 mg/m'-years) Nn Cough Morning Day or night Three months in year Phlegm Morning Oay or night Three months in year Periods ct coggn and pniegm Breathlessness Wheezing/chest tightness S 104 6 16.3 3 6.1 6 16.3 9 18.4 S 184 3 6.1 10 20.8 2 4.1 n 9.1' 7 S.8 6 5.0 22 184 13 10.7 14 11.6 1 04 22 184 10 64 6 17.6 5 14.7 4 11.8 6 234 6 17.6 6 17.6 - 0.0 6 17.6 8 235 * p<0.01 tCochran-Mantei-Haenszel lest of general association controlling for age and cigarette smoking). unexposed group (table 6). Stratified analyses showed that age, but not smoking, was significantly associat ed with radiological small opacities with profusion 20/1 (at least two readers). Altogether 17 persons had small opacities of pro fusion 1/0 and greater in their radiographs, as read by at least two readers. Four persons bad radiological profusion 1/1, and one had 1/2 profusion. No one in the unexposed group had radiological profusion greater than 1/0. There was a twofold higher preva lence of radiological opacities of profusion 1/0 or greater in the high-exposure group as compared with the low-exposure group. Radiological small opacities of profusion 1/1 and greater were seen only in the high- exposure group. Similar results were obtained when the radiographic readings for each reader were used in the analyses. The predominant types of opacities were irregular although the readers differed in their interpretation, particularly with respect to the shape but not the size of the opaci ties (which were all read as <0.5 mm in diameter). 'Reader one read mostly irregular opacities, reader two read more irregular than rounded opacities, and reader three read more rounded than irregular opacities (ta ble 7). Discussion In a cross-sectional study, the reference group is the most appropriately chosen from within the same fac- 56 22531004 BFG21387 22531003 il! iO 1 1V Table 6. Prevalence of raoiological coaeities by reader and exposure group. Parameters Unexposso* (N > 27) N% Low exooaure* (N a 61) N% Hlgn exooaure* (N >29) M% Reader i Prolusion a 0/1 Profusion a 1)0 Prolusion a m Reader 2 Prolusion a 011 Prolusion a 110 Prolusion a 1/0 Reader 3 Profusion zQn Profusion a 1/0 Profusion a 1/1 Two or more readers Profusion aQfl Profusion a 1/0 Prolusion a in 7 25.9 1 3.7 1 3.7 _A 14.6 0.0 -- 0.0 _4 14.6 0.0 -- 0.0 4 14.8 0.0 -- 0JO 49 60.5 13 16.0 -- 0.0 38 46.9 12 14.6 -- 0.0 32 39J 14 17.3 6 9.9 37 45.7 10 12.3 -- 0.0 21 72.4* 8 27 6* 4 13.8' 16 S5.2" a 27.6* 4 13.5'* 13 44.5* 7 24.1* 6 20.1** 16 55.2* 7 24.1* 6 17.2** * Mean age ol the group 4i,i (SO 12.<I years with seven (26 %) nonsmokers. three (11 H) ex-smokers, ano 17 (63 %) current smokers. 1 Low exposures'< 10 mg/m'-years: mean age of the group 36.2 (SO iOJ) years with 60 (50 %) nonsmokers, seven <6 V.) exsmokers. and 53 (44 %) current smoxers. * High exposures a to mg/m*-years; mean age of the group 4i.O(SO 9.1) years with nine (26 %> nonsmokers, nine (26 %) ex- smokers. and 16 (47 14) current smokers. ' PsO.05, ** P<0.01 (Cocnran-Mantei-Haenszel test of general association, controlling lor age ano smoking status). Table 7. Distribution of raoioiogical types by reader ano exposure group. Unexoosed Roynaeo Irregular Low exposure `-years) Rounded Irregular Reader J Profusion aO/i Profusion a 1/0 Profusion a 1/1 Reader Profusion a 0/1 Prolusion a 1/0 Prolusion a 1/1 Reader 3 Profusion a 011 Profusion a 1/0 Profusion a 1/1 34 --1 --1 31 ---- ---- 31 ~-- ---- 49 -- 13 ---- 1 27 46 ---- 24 8 10 5 3. High exposure 1*10 mg/tn `years) Rounded Irregular 21 --8 88 5 3 94 52 tory if it is certain that it is indeed unexposed. Our en vironmental assessment clearly indicated a secondary exposure in the ambient air for almost all of the work ers in these factories; and this secondary exposure was likely in itself to produce some degree of pulmonary effects. It was therefore necessary to choose an exter nal comparison group, which we believed was ap propriate for the study since it was an occupational counterpart in other industrial undertakings. The va lidity of this group was well supported externally by the good approximation of their lung functions to predicted norms from other independent population samples. The previous dust levels in the factories were not known, but there were reasons to suppose that they were probably higher than current levels. Since only current dust levels were known, it should be empha sized that the estimates of cumulative PVC dust ex posure were not based on actual dust exposure levels. The data in this study were, therefore, used only for categorizing broad groups of PVC-ctposed subjects and not for deriving quantitative exposurc-reponse relationships. Exogenous sources of VCM and thermal decompo sition products may be ruled out as the cause of the observed pulmonary effects since VCM exposure from residues in the PVC powder was negligible and irri tant and toxic gases like hydrochloric acid. VCM. phosgene, and chlorine are only formed at tempera tures in excess of 22S*C. We also made measurements 57 BFG21388 at the mixer and extruder, and hydrochloric acid and VCM were not detectable. However, it is more diffi cult to exclude the possibility that the radiological opacities could also have resulted from additives con taining radio-dense calcium and barium compounds in the mixture, although only small quantities of these substances were used. The radiological readings were all done by physicians experienced in the assessment of radiographs for pneu moconiosis, and standard guidelines were used under controlled conditions so as to eliminatesubjective bias and produce unequivocal case identification. Under the circumstances, the effects of aging and cigarette smok ing were unlikely to produce radiological opacities more profuse than category I/O. There should there fore be little if any doubt that at least radiological pro fusion 1/1 in five workers indeed represented PVC pneumoconiosis. Both diffuse micronodular and linear-reticular opacities have been described in case reports of PVC pneumoconiosis, characterized histopathologically as pulmonary' fibrosis associated with granulomatous lesions (1. 13). Similar histological changes were ob served in experimental studies with guinea pigs and rats (14. 15). As in previous epidemiologic studies (3. 5. 7), the present study indicated that the radiological lesions arising from P VC dust exposure were of limit ed profusions with a predominance of irregular small opacities. The reported prevalence of radiological le sions varied greatly among the studies. It is, however, difficult to make vaiid comparisons among the studies because of differences in procedures and criteria for radiological case definition, although in two of the studies, ILO standard films and radiological classifi cation were employed for reading by a minimum of two or three readers i5, "i. Furthermore, the preva lence of radiological small opacities may be expected to vary with the level of PVC dust exposure, but such measurements were only performed in one study (6). In the study by Soutar et al (6), the estimated dust in dex of 14 mg/mJ-years appeared to be comparable to that of the high-exposure group in our study, but in both studies, past levels of PVC dust exposure was un known. Previous reports of an association between PVC ex posure and a restrictive type of lung function impair ment (2, 3. 6) was supported by the findings of the present study. The average lung function loss was modest, but. given individual variation in responses to PVC exposure, a few persons in any exposed popu lation may be expected to experience clinically signifi cant lung function impairment. PVC exposure was also found to be associated with an increased prevalence of dyspnea in the study by Soutar et al (6). No such association was demonstrated in our study, but it should be noted that, whereas the study by Soutar et al included past workers, we could only study current workers who might probably be overrepresented by those whose functional impairment was not severe 58 enough to prevent them from continuing with their rent employment. We did. however, find an incret prevalence of wheezing or chest tightness, and i findings have not been reported in previous stuc Apparently, responses to these symptoms were rcelicited in previous studies. The possibility of re* ble airway obstruction, however, corroborates wur results of a recent study showing across-shift FE changes in PVC fabrication workers (9). and S fS report of bronchia] asthma from inhalations) pr> cation tests with PVC dust (16), and should there be further investigated. Acknowledgments This study was conducted with research x RP880371 from the National University of Sings and the support and assistance of the Singapore. Tuberculosis Association. We also wish to than Moozoomdar for his interest and special assist: and the Permanent Secretary of the Ministry of Lefor permission to publish this report. References I. Stertde B. Lapis K. Nemes A, Pinter A. Pr.ecrr.o. sis caused bv ihe inhalation of polyvinyl chier.cs Med Lav 1970:61:433--4 Z. Miller A. Teirstetn AS. Chuang M. Seliko:: f. Cr in pulmonary function in workers exposed :? v;--. ride and polwinyl chloride. Ann NY Acad Sc: 246:42-52.' 3. Liills R. Anderson H. Miller A. Selikoff l. ?u:t changes among vinyj chloride polvmerizsuor. *,. Chest 1976;2:299--305. 4. Gamble J, Liu S. McMtchael AJ, Waxweile: R.: of occupational and non-occvpational factors respiratorv svttem of vinvl chloride and other wJ Occup Med 197J;[8:6S9--70. J. Mastrangeilo CT, Mar.no M. Marcer G. et a.'. Pc chloride pneumoconiosis: epidemiological st'jc;posed workers, J Occup Med ]979:21 :5a0--2. 6. SoutarCA, Copland LA. Thornlev PE. et al. ; ologicaJ study of respiratory disease in workers e to polyvinylchloride dun. Thorax 1983:35:644 7. ChiversCR. Lawrence-JonesC. PaddleGM. Lur. tion in workers exposed to poiyvinvl chloride c J lnd Med 1978:37:147--51. 5. Baser M. Tockman MS. Kennedy TP. Pulmcra; tion and respiratory symptoms in poiytir.yi: fabrication workers. Am Rev Respir Dis 195* 203--8. 9. Ernst P. De Guire L. Armstrong B. Theriault structive and restrictive ventilatory impairment inyichioride fabrication workers. Am J Ir.d NU 14:273--9. >0. Prodan L. Sueiu I. Pisiaru V. ilea E. Paseu perimcntal chronic poisoning with vinyl chlonde chloroethene). Ann NY Acad Set I97J;244:I* 11. Da Costa JL. Goh BK. Prediction nomograms function measurements in adult Chinese. Singap J 1971:12,4:193--8. 12. Zee KO. Ventilatory function in normal induttr: ers in Singapore. Ann Acad Med Sincaycr. tsuppil:3S7--93. 13. Arnaud A, Pommter de Santi P. Gatfce L. BFG21389 JO Ol CO h* o o cn Charpin J. Polyvinyl chloride pneumoconiosis. Thorax 1971:33:19--25. 14. Frongia N. Spinazzola A. Bucarelfi A. Experimental pul monary lesions from prolonged inhalations of PVC dust in a work environment. Med Lav 1974;65:321-42. 15. Agarwal DK, Kaw JL, Srivastava SP. Seth PK. Some MocbemicaJ and histopaihological changes mthrmi by polyvinylchloride dust in rat hmg. Environ Res 1971* 16-J33--it. 3 6. Let HS. Yap J. Wang YT. Lee CS, Tan JCT. Poh SC. Occupational asthma due to unhealed potyvfeyichloride resin dust. Br J lnd Med 1989;46:120-2. Appendix Agreement between the readers of the radiographs Reader 2 01-- 010 0/1 1/0 1/1 1/2 Reader 1 Reader 3 Of-- 0/0 on 1/0 1/1 1/2 3 <3 21 2 _ _ __ 01-- 010 . A. 4 24 9 1 _ on _ 10 5 1 -- 1/0 ____ 1 2 ___ i/l -- -------- 1 1/2 Reacer2 01-- 0/0 on 1/0 in 1/2 m. 8 63 14 3---- -- 7 18 2 -- -- -- 1 4 2-- -- -- 2 8 3-- -- ---- ---- 1 Kendall's tau-9 0.637 <SE 0.041) Kendairs iau-a 0.632 (SE 0.054) Reader 3 or-- 0/0 0/1 1/0 in 1/2 Reader 1 01-- 0/0 0/1 1/0 1/1 1/2 ._ ___ 55 20 _5 17 S 3---- 5 1-- 2 0-- -- -- 3 7 3-- -- ------ -- 1 Kendall's tau-B 0.574 (SE 0.0543 Received for publication: 9 May 1990 22531007 BFG21390 59 ((( HYDRO tot POLYMERS Vinyls Division Mr R T Gottesman Executive Director The Vinyl Institute Wayne Interch. Plaza II 155 Route 46 West Wayne, NJ 07470 USA Your ref. Our ref. HMC/PAM You letter of Date 16 April 1991 Dear Roy, PVC DUST I draw your attention to the attached paper, together with the handwritten note from our own Medical Advisor. You will be advised of the results of a critique of /the paper. Yours sincerely. h n ciayton Senior Environmental Advisor 800TZ2 BFG21391 ((C HYDRO Itotf POLYMERS Vinyls Division Mr- ftutll Chjfc* Hydro Polymers Lid. Newton Aycfifte, Co. Durtunt, 0L56EA, England. Telephone: National: (032S) 300555. Internal: (44 325) 300555. Fax: (0325) 300815. Telex: 58322 Internal Memorandum fT, Daw //V 9/ hjuJr '- - ' */' 4*uJ**^ 2.1 (fill %iUTyHyU*"' LU * ,,0, iUj * ** r~ if~ hrfJr~ 600T2: BFG21392