Document QMLN7j7pyaw8r0kGnZOydEZzR

Original Articles ITEM 6 COPIED BY MCA FOR DISTRIBUTION TO THE VINYL CHLORIDE TECHNICAL PANEL, NOVEMBER II, 1976, MR. MILTON FREIFELD Effect of Occupational and Journal of Occupational Medicina October 1976 Voi. 16 No. 10 Nonoccupational Factors on Respiratory System of Vinyl Chloride and Other Workers John Gamble, Ph.D.; Shuguey Liu, M.S.; A. J. McMichael M.D., Ph.D.; and Richard J. Waxweiler, M.S.I.E. There are suggestions in the literature that vinyl chloride (VC) acts as a lung irritant Respiratory questionnaires and lung function tests were administered to 174 chemical (VC) workers. 81 polyvinyl chloride (PVC) workers, 72 former VC workers, and 136 rubber workers, and 68 maintenance workers with eiposure to VC, PVC, and rubber. Except for small air* ways obstruction associated with rubber, increased respiratory symptoms and decreased pulmonary function were not associated with working in chemicals, plastics, or rubber. Some increases in baseline pulmonary function were associated with VC eiposure. Acute reductions in pulmonary function were observed in smokers working in chemicals, plastics, and rubber. Heavier cigarette smokers over 40 years of age had the most adversely affected respiratory system. Work was not associated with chronic respiratory effects, but all exposure groups experienced some acute respiratory insult At high exposures, vinyl chloride (VC! is a nervous svstem depressant and in fact was investigated as a possible anesthetic, but was not used because of circulatory and cardiac effects at concentrations of 10-20 vol. V' tn the late 1960's, acroosteofvs's was associated with the polymerization of VC to form polvvmvl chloride iPVC!.?** Early in 1974, four fatal cases of angiosarcoma of the liver were reported in reactor operators working in a VCpofvmenzation plant.' Subsequently the disease has been discovered among VC workers aft over the world. Experimental and epidemiologic studies suggest that exposure to VC may carry an increased risk of respiratory impairment.*"4 As a result, tne Occupational Health Studies Croup OHSG- at the University of nnm OcckmikymI Hralth Studies Oni^ Schnri ol Pi^lic NeaRfi. Uruwnitv ri North Cifolirvi Chpvl HiH NC 2'514 keornt requests in NCN6 Plszi. Sort* )2. Owe** Hil sC 27X14 (Dr G,mbte> Journal of Occupational Medicine/Vol. 18. No. 10/0ctober 1976 North Carolina and the National Institute of Occupational Safety and Health (NIOSH) and CDC jointly carried out an epidemiologic study of VC-PVC workers. A part of this study was the investiga tion of respiratory function and symptoms in currently employed VC and PVC workers, former VC workers, and a sample of control rubber workers employed m the same plant. Methods and Materials The plant under study has three maior divisions The chemical plant produces primarily polyvinyl chloride (PVC) resin, although some copolvmers such as vmylidene chloride and styrenebutadiene are also produced. The polymers are either shipped or used m the Film and Sheeting division of this same plant m the production of plastic products. Film and Sheeting division (plastics; is m a building adjacent to the Chemical Plant, which also contains the Rubber Products division manufacturing primarily tires and tubes. All workers currently employed in the VC-PVC plants were invited for examination. A sample of 13S rubber workers from cleaner areas of the rubber division (i.e,, tire building, final inspection, shipping and receiving) and without prior exposure to either VC or PVC. were selected and erouomatched with the VC workers on age and sex A total of "1 lormer VC workers and 68 maintenance workers were aiso examined The response rate varied from a low ot 62% in rubber workers to 77% m chemical workers. Clinical, smoking and occuoational histones, complete physical examinations, chest roentgenogtams. sputum cytology, symptoms, blood and urine chemistries were obtained on all 531 workers and will be reported elsewhere The British Medical Research Council respiratory Questionnaire was administered bv trained medical interviewers. Each worker performed a minimum of five forced exhalations, seated and witn a noseclip. The three best performances were selected on the basis of forced expiratory volume in 1 second 1FEV) and forced vital capacity (FVCi within 10% of each other, and acceptable re producibility of the flow-volume curve. In add'lion to FEV and 659 RSV 0001640 t FVC. expired flow at 25% WF25). 50% 'FEF>. id Tj% 'FF*s1 oT exhaled FVC were obtained. At least tnree single-breath nitrogen tests were also performed. Recommended procedures and selec tion criteria were followed for obtaining closing volume 'ex pressed as ratio of closing volume to vital capacity. CV'VC)." in addition, a random sample of fifty-six VC. PVC and rubber workers were administered lung function tests betore work and again after work. The difference m flow rates 1$ calculated as after before/mean with afterwork flow rates measured using the maxi mum pre-exposure FVC. The following questions were of interest m this studv: 1. What are the effects of work on respiratory symptoms and function! Symptoms and baseline lung function were analyzed ac cording to three work exposure categories ia> current 10b (hourly VC salary VC. PVC. rubber, maintenance, former chemical): ib) all jobs, past and present (only in VC. only m PVC only in rubber, or in a combination of the three! In this mixed exposure group an analysis of covariance was used to sort out the contributions of the VC. PVC. and rubber work experience to baseline pulmonary function: id man-momhs of exposure to VC: All VC jobs were given a high (10). medium (3) or low Hi exposure rating. Time 'in months) spent in each job multiplied bv tne exposure index provided a cumulative exposure to VC. This cumulative exposure sc' 'CESl was then compared to baseline pulmonary function. -e association of dose years worked in the exposure Co gories or CESl and baseline lung function were assessed by calculating lung function regression equations for each smoking category of the total population. Then, within each exposure group, actual values of each smoking category were expressed as a percentage of expected values for all workers m that same smoking category. In this way. the effect of work exposure on lung function was adiusted for differences m age. height and smoking between exposure categories. 2 What are the potential hazards of work exposure as measured by changes in pulmonary function over a work shift t APF)? A reduction in lung function suggests the likelihood of some harmful exposure in the working environment. 3. Are symptoms rates and lung function parameters com parable to other occupation groups? Because the PVC and rubber control groups were themselves exposed to varied levels oi dust and fumes, comparisons with other studies are made. Results The age-smoking distribution of the population is shown in Table 1. Slightly over haH of the population were smokers. 20% nonsmokers, and 16% exsmokers. The exsmdkers were older than the other smoking catego. wirh proportionally fewer pxsmokers m the .39 vear age group. Smokers and nonsmokers hud approximately the same distribution m all age groups although a higher proportion of nnnsmukers were older, and a higher propor tion of smokers were m the middie age groups. None of the lignt smokers ( < 1 pack/dayi smoked more than 25 pack-vears. and they were equally distributed in the < 25 paefc-vears category Most '> 1 `'oi ot the hcavv smokers 1 in pack dayi were in the > 25 pack-vear category: 25% smoked 10-25 pack-vears. and 14% < 10 pack-years. Table 2 shows the distribution of symptoms related to smoking and age. Prevalence of cough, phlegm, and persistent cough and phlegm did not increase with age. Breathlessness increased slightly but steadily with age. with the oldest age group reporting a rate of breathlessness 2.5 times greater than the youngest age group. Smoking had a strong effect that was dose-related for alf respiratory symptoms. Light smokers 1 <1 pack/day) had the same svmptom rate for cough, phlegm, and persistent cough and phlegm as exsmokers and pipe or cigar smokers. Exsmokers, pipe, cigar, and < 1 pack/day smokers had similar rates 01 breathlessness. Because of the potential confounding effects of age and smoking, comparison of symptoms m each exposure category were adjusted for smoking and age differences. Table 3 shows the prevalence of respiratorv symptoms according to current 10b- The salaried chemical workers consistently had the lowest prevalence for all symptoms. Plastics, former chemical, and maintenance workers reported the highest rates for cough, phlegm, and per sistent cough and phlegm: rubber and hourly chemical workers were intermediate for these symptoms. All workers except the salary chemical workers observed similar rates of breathlessness. Table 4 reports the age and smoking adiusted prevalence of respiratory symptoms m workers working only >n the rubber division, only m plastics, and only in the chemical plant. Main tenance workers move back and forth among chemical, plastics, and rubber, with no epidemiologicatlv appropriate records kept of time spent in any of these areas. The mixed group comprised tlvose who had worked m two or more exposure categories. The plastics only and chemical plant only workers had marked reduc tions m reported symptoms when compared to all currently em ployed workers in these same categories. Svmptom rates for the mixed group were stightlv higher than observed in the total population, and similar to the former chemical group. Those working onlv in chemical, plastics, or rubber appear to be a select group of healthier workers A hi^n proportion of fhose with symp toms in current job categories had a mixed exposure of ruboer. chemicals and'or plastics TaMa 1. -- Afo-Stnokiftf Composition of Study Population. *----1 ItftM Nantmowr' EnmOwt Smoir J X'* M C.|*i M n (V ?6 (24 3' i '51 5? is: 61 ; 3 6' tor (20-2) 3041 1X1 is m j) 1 ! 901 52 '51 S' 10 '112' 9 (11.11 4(M9 M 1X1 27 f!6'> ?9 '179' 92 56 8' it ' 86i 192 (JOS) 50-SJ N IXI V h? 91 35 (23 2: '5 ' 7` .4 : V 191 <210 in It 1X1 9 ic 9' I uS 21 & *2' 3 ? ; e> 22 < 4 1) Tow n <x *r Toufl 13! 2C2> 94 :58 .n: 5:: r 5 9' 931 'tonwnow > w ynxa KU lwr IX ; jotiict * t iiKtra TlxvnoMr = no itoccM wnaxmo men m*n 1 M dos not vj utmm i got <r fSmaw * rot yncMd men (tun IK eigscttn m i iiteixnt ml Ra tmawe wiiiwi tr at: ** Pn imam *f otso tw ci(ciib ot xcuM n ms aiqin Kex ^ Cif* = tN tm* no vrac < ata a cij *o tot M net smaa aproncs a now m wnaMd tuOTtt** V * im qr mao. Prau|a an irwmu m % a tows, wonaiw > emm paunum 660 Occupational and Nonoccupationai Factors on the Respiratory System ol VC Workers/GamOle et al ftSV 0001641 Smtkftf Ctwtwy Nmmd* EumM Ail *ro*t l oao/ciy l paa/tar >1 paa/day pa <m Ci| All * Cawaary 29 3039 AO-49 50 59 >60 Tatta 2. -- ftaapmtory Symptom** by Aft and Smoklnf. N 108 (20 3*) 84 (15.1*1 793 <55 0*1 61 (115%) 143 06 9*1 M (166*1 <7 (8 9*1 531 Ct|ft 18i % 56 71 216 98 18 9 34 1 85 14 9 Pt>fefn 1A2 * 13 131 26* 131 231 391 106 19.2 PtnMH CMC* & ft 21 60 137 16 ill 261 21 92 107 (20 2\) 89 (16 8*1 162 (30.5*1 151 (28 4*) 72 4 1*) 14 0 157 154 146 136 206 157 204 its 227 93 90 105 71 91 * = Scans Sr enan* *on Sntrjn Mm Resawoi Council ftcsoraury Wiionn t = 1 miumi ts3 KMtimi traattiWinwa ft ii; 19 3t 26 St 23 3t 189 409 IS2T 71 2t 12.51 19.1 216 26 5 318 Figures 1-6 display the regressions oi pulmonary function tests for the different smoking categories Age and height significantly affected FEV and FVC values: age. but not height, was a statistically significant predictor of flow rates and dosing volume (CV/VC). Heavy smokers (1 pack/dav) had markedly reduced ventilatory capacity compared to ocher smoking groups exceot for FVC where smoking did not significantly affect lung volume1. Lung function values of exsmokers decreased at a rate in termediate between the heavy smoker and nonsmoker groups. Pipe or cigar smokers resembled nonsmokers for FEV. FEFsa. and FEFn. but resembled exsmokers for FEFjs-'s and closing volume (CV/VC). Except for CV/VC. the least reduction of ventilatory capacity was observed in the light smoker '< 1 pack/dav* group. All smokers had similar functional reductions of CVVC with in creasing age. Current smoking behavior showed a better correlation with pulmonary function than did pack-years ot smoking, and for this reason regressions based on current smoking categories were used in calculating predicted lung function values Table 5 summarizes the prevalence of impaired lung function as related to age and smoking. Except for FVC and CVVC. pulmonary function impairment 'see Table 5 for definitions' con sistently increased with age: and for all parameters consistently in creased with increased smoking. Impairment rates for FEF:s*s. FEFso/FVC and CV/VC were significantly higher for smokers than nonsmoking categories: the smaller number of pipe or cigar smokers precluded them from achieving statistically significant dif ferences. Age and smoking were then analyzed simultaneously Regressions of pulmonary function with age 'Figs 1-6< suggested that after about age 40. smokers oi pack/dav clearly had lower lung function values than the other categories ot smokers. As there was little difference m prevalence of impairment among ex smokers. nonsmokers and pipe or cigar smoker categories, they were combined into a nonsmoker category, divided into age groups above and below 40 years of age. and compared with cigarette smokers 5mokers and nonsmokers in the younger aee group had similar rates ot lung function impairment Smokers o%f" tjiiOWii Coufti 1 rt 2 *><#("> 1 2 PMWH Cttr(n M PtiO*ni fraatfttuntuf (&>! 2. 3 4) M Ac* <***J <ail wam (tai Ttbte 3. -- Aft Md SflldUftf Adfvtttf hrtrtwnct Ratn f RMvntary Symptom* by Curront Job. ftobbai * 103 IS ! 59 Pft**** * 201 261 136 H*ity * 148 155 63 Sawy * *7 a 35 Formar Oi*"*#1 * 155 75 9 11 4 Muonic* * 16 5 27 : 13 ' 20 6* 138 40 4 ii:r 221 81 14 1 11361 21 6 124 411 <12 81 15' 50 36 5 16 9) 26 9* 72 43 ; 15 71 19 4 is' ;:; 695 ' 2 U' 692 1 25) 695 < 221 696 ( 2 96) 69 7 2 8; 59 4 : 8' 1749 C3 31* 1 BOA 17' 3) 184 5 1X7) 1 77 4 (25 7f .83 9 7'5i ;6 : ;6: * * 1 <nmf T-3 rnwnj Journal of Occupational Medione/Vol. 18. No lQ/Octotoer 1976 A* .55 :i: 92 2124 531 *2 1 ' hz 5 At -V 551 RSV 0001642 <2. *t fl( 1. -- PrtdictiM Eoustton for FVC in Total Population bp Smoking. 40 years of age had significantly increased impairment compared to thetr nonsmoking counterparts. A synergistic effect of age and smoking was not observed for FVC (impairment was not affected by age or smoking) and CV/VC (both young and oW smokers had rates of impairment higher than nonsmokers at any age). To preclude confounding effects of age. height, and smoking in assessing the importance of occupational exposure, mean percent pulmonary function for each |ob group was calculated by dividing individual pulmonary function values by predicted values derived from the appropriate smoking category, and calculating the mean. Smoking-adjusted impairment rates were directly adjusted FI* i -- Frodlctton Epoottois tor FEVi to Totoi Fopotoltoa bp Smoking. using the smoking distribution of the standard (total! population Baseline lung function as measured by mean percent predicted was (he same in all current |ob groups. Table 6 summarizes the prevalence of impaired pulmonary function by current |ob. Former chemical workers tended to have the highest impairment, salarv chemical workers the lowest. The other job categories generally had impairment rates berweeti these extremes. The effect of duration of exposure on lung function was then analyzed. Age, height, and smoking variables were adiusted m the manner previously described. Predictive equations were Tibi* *. -- ip ito Smoking Minted Fronton* Rato* of PtHokitory Symptom bp Eipowro Catefoftoo- * s 1 nuM| f = 3 mo*M| 662 Occupational and Nonoccupational Factors or the Respiratory Svstem of VC Workers/Gamble et al RSV 0001643 Fit * -- Pr6ettoa EQMtlora tar FEF In tM Nytatlii by tata| *--*--1 CWtaW WwUMf (OMW SmMr a All <29 30-39 4049 $0-59 >60 A< Ctawy * toranwtut. i 39 $nanfi 39 All <- 39 HopvkMr* 2. *0 $m<Mn _, 40 All i 40 Ait 'NensmoMn All. JflKMn Ttbte 5. -- Prwainicn Rita f Impainrf Pnlrnomry FtmctiMt by Aft and Snobby. N Ft* nc FEfa-71 FK % % % 10* 259 46 M ill 71 292 4U 84 42 291 14 9 531 384 81 63 10 7 194 84 145 FT7M FVC % 24 21 14J 13 102 rcm FVC % 314 57.1 524 362 47$ 102 164 74 I0J 19 65 19 29.1 10.1 90 1 1 33 7 162 364 . 84) 130 99 $19 351 604 60 224 192 75 5 7? *5 $ 9! 727 18? 77 7 77 208 10* 11 1 3 182 119 22 7 'E B 19 3 196 21 9 85 >? i $ 189 16? 364 52 to o; 52 5 173 SI 4 13 292 23 7 '5 2 13$ 478 58 179 152 642 219 314 3$ 92 46 41 1 292 434 14 19$ 14 * 42* 'HmiiMi=wwtwn nwi m c< imwi ^u*non>r Factions FtY/tVC <0 7$ FVCU 111 'hum! 002$ lajt) 4241 < 0 SO (from Iftorwa 31) FIFISn/0040 Owftl 0050 <*t> * * iJ9 < 02$ Ilrgm M gww4 fEFta/TW <05* FEF7vrc < ojo CV/VC/0 $42 0 357 Itatl > IJO tao* nton <an Wn*ne* 34) 1*1 imsny. 2=2 imm| 3s) mun|. 44 u| 5= $ nw*t. $*( imtso* Dc... K5V Journal of Oauutional Medicine/Vol 18. No 10/0ctober 1976 cv/vc 1$ a>> 7 3' 16.1* 44 10 5 ).$' 10.21 UJ' IJ7> 0 i3 ;3 L ! 85 0: 1'9 11 6r 3V 16 1* 000X644 663 //<""' // /V/A////?//'/^,v / /// / **'/ fi/ // y //'/ 4#V/*/* Wm t--*u N~rc> o. m*/u**t </* je h !, M 99 * Fig 9. -- rrofbctkn tfwibM for FEFts in ToUl Population Or Smoking. fl| 6. -- Probation Equatiom tor Clumi Vokmo/Vltal CaMcfty (CV/VC) In Total Poaolatioo by Smokmi calculated using length of work in years as the independent vari able. r.e.. predicted pulmonary function a % predicted + % change m pulmonary function/year spent m exposure category. Table 7 summarizes regression for which a significant change oc curred. For exposure category 1 (rubber only, chemical only, plastics only), rubber workers observed a significant decrease of 0.8%/year in FEFry plastics workers a decrease of -1%/vear. All other significant changes were increases in lung function. Health-related selective migration of workers is a potential source of bias in a cross-sectional studv In ar> attempt to take ac count of this, the effects of working in rubber and chemical, rufcv ber and plastics, chemical and plastics, rubber, chemical, and plastics, or any one alone, were examined by analysis of covariance 'Table 7). Bv backwards elimination method, exposure variables not statistically significant (p > 0.05' were sequentially re moved until onlv the most significant exposure variables remained in the model. The analysis was done first on the total population (No- 21 then on the mixed exposure group (No. 3) and finally on the combination of categories within the mixed exposure group (Nos. 4-6). For the total population, working in chemicals was as sociated with increased FEV. FEFij.'s. FEFjs. and FEFso. The only re ductions in ventilatorv capacity were observed in FEF-s, a highly significant reduction associated with rubber, and increased CV/VC, a functional decrease associated with plastics. The analysis of the mixed exoosure groups exposure categories 3-6' tended to support the results observed in the total population. TaMa I. -- Aju Mb Snaking Adjuitod Prmloneo at impairob Pulmonary Function* by Currant Job. PotoMffy r--um u rtv*vc rvc *tf?srs fJFM/niC nrn'rvc cv *c IX <1 3X 14 15 9 ::i 46 4 62` `QarwNon 9 imateof * Tw 5 1 = 1 nwq ? =2 rniunf 6*$ flMMIt J=J imot| naan li 32 6* \12 u; ii ' ti* 12 r Cmiu Ju Chornm Hoarty 124 31 4% 64 12 3 62 if,! 13 8 Sabrr 50 29 'S Cl ,4 ! 0 336 36 Fomor Qwnical 'l UTS 85 25 2 1! 6*4 12 5* Mamrynanc* 68 3! 4X, :: l .: 5 5 45 6 TV u 8: 5 :: 4:5 10 5 664 Occupational and Nonocajpatioral Factors on the Respiratory System of VC Workers/Gamtole et al ftsv OOOI645 Tata 1. -- Selected Predtetlon fttpiuieiK far Pulmonary Function Related to fapowre. A|, Heiftit and Smgkwif Admttad. tqtoM cmonr i 2 } j i 2 4 6 1 2 3 4 6 1 2 i 1 2 3 4 S 2 3 5 s fniVNi Mutol Fwettai FEV s FVC FEF2S-7S FEF2S FEFSO FEF7S CV/VC % proa* 944% 992 1X4 93 3 M3 93.6 940 107.3 944 910 940 964 106.0 9 4 940 942 1092 1114 1X5 944 1X9 96 5 94.3 97.6 107.9 92.7 * % Ctoyr *0 47% -0 15 026 +034 a 62 *066 *033 4.94 *0 46 *049 *0 36 *035 4346 *0 90 *099 *030 0 7? 10 067 497 2 30 10 *043 +046 4 75 +1 16 ft EecO Var Spent In (omu Catacary S*toT Pwrnai toy Cnemai Rutter PVC toy PVC Maury eternal toy Ctemoi Ritt* Cternal Moury Ctemoi Ony Ctemoi Ctemicjl Putt* tiwmi ttowy Ctenuew Ony Ctemoi Rutt* Ony PVC Ony Ritter Rutter RltiMT MOV PVC PVC Cternai PVC ' Euowi Citeiary 1 tt*m Ony. PVC Qe*t. Ownm & SI toy Jiow PiMn iRiM*. Ctermai WO 3 =Miud Enact** (RuBM 4 Chamal: Plata t Cimral; Rt40* 4 PMo. flu00*. Ctornol 4 Pttstal -- RutMr 4 Plata (N-521 5=Ri t Ownal (N=8) 6- RtfB*. CtamcM 4 Plata <NS1I n VNt fm % Cluafft 0 02 0 010 0.04 004 0002 0.009 004 003 0.003 000$ 0.10 0 07 002 0.03 009 001 0.07 0.0001 0 001 0.004 004 004 on on 005 Work in the chemical plant was associated primarily with in creased flow measured over mid vital capacity Work in plastics was associated with functional reductions of from 0.4 to 1.2%/vear m CV/VC- The most consistent and greatest changes were reductions of from -0.7 to 2.3%/year in expired flow rates at low lung volumes (FEFrsh associated with work m rubber. Table 8 summarizes the relation of pulmonary function and cumulative exposure to vinyt chloride Isee Table 8 for definition of CES-cumulative exposure score! Increasing exposure to VC in all workers ever exposed to VC was not associated with anv signifi cant reduction in pulmonary function. The general tendency was for pulmonary function to improve with increasing exposure. Only reductions in FVC approached statistical significance Dividing the group into those with current VC exposure, and those that worked m chermcai or plastics in the past 'former chemical: and repeating the analysis produced the same results. The relation between respiratory symptoms and baseline pulmonary function is summarized m Fig 7 All respiratory svm^ toms were significantly associated with reduction m expiratorv flow (FEFis rs, FEF:s) Cough, phlegm, and persistent cough and phlegm were significantly associated with reductions m FEFso. Those with cough 2. phlegm 2 and persistent cough and phlegm had reduced percent predicted CV/VC Reduced FEFrs was asso ciated with symptoms of cough and persistent cough and phlegm. In addition to baseline pulmonary function. 56 workers were Journal of Occuoat'^l Medicine/Vol 18. No. 10/October 1976 tested before work and again after work. Since the workers were also taking physical exams, actual working time averaged about 4hours. As there were about twice as many smokers <82%i among chemical workers as plastics i36'! and rubber (41%i workers, acute effects were compared m cigarette smokers and all others combined (nonsmokersi. Current smokers observed significant Tata 4. -- *|i Halftit and Smpklni Adiuitnd ftt|roaioni sf Parcont Prodletad'Pulmonary Function to Chemical and formor Chemical Norton IK = 196} by Cumulative WpijhiM Exposure* to Vinyl Chloride. PubMten FihlIUh FEV FVC FEFJS7S FEF2S rir FEF7S CV-VC Imp topi !% prMletM) 94 9% 1X4 964 960 9`9 975 102 Sleet r% doifi/CCS** *0 14% 416 -CU -C 53 *0 35 40 434 el Sleet 04? 013 0 04 0 02 o :9 C 17 0 24 ' CCS = aixiiiN eieosur* icon *11 |4M m in* cmtioi Mm m ntaa to C hooha a NH /TWfcsWBinMM 250 ppm] *Mwn <TW aanm 76 opml. mi iTW* MCrametiy 25 CBni CCS m amnia im.mey"* <nanm nmc ir* iturna aOBMt ntn Chyh = 10 mtun =3 ten * !) to tint >cfi. M wrnmnj mWiOH tlt< = 0 - 247? BWai umnn 665 KSV 0001646 9^ BWEATHLlSStoESS *9 :\A V 90 9 12 3 4 12 3 4 1234 >234 ^TPgftSlSTANT COUGH ana PHLEGM no Z7 >234 1234 1234 u 99 5 90*- a i 1,0 o phlegm ** 03 et- 9f- of* L 03 r cough look' " 901- -L, 0 i 2 FvC FEV cv/vc Fig 7. -- Ptrctffl Pradictad Pulmonary Function in Workor* With and Without RatOiratary Symptom* Adjustad by Ag. HtigM and Smoking. reductions in both How J volumes Nonsmnkrr'- ob'-crsod in creases m FVC ana peak now but nthe' lung tunt imn p.u.imrn.'r*. decreased. s>gniricant onlv for FFFsn 'Tjble 9i Smokers in alt i[`b groups hod reductions m vcnnljtorv canaotv. the c'f'atrt df-mment occurring in flows at low lung volumes The reductions vse'e ot the same order or magnitude for ail three exposure group!- but were Significant only for vmvl chloride and rubber workers Except for reductions over the shift of FEfso and FfF's in nonsmoking rub ber workers, ventilatory capacity of nonsmokers did not change significantly from zero. Discussion This study was stimulated by the finding of an increased inci dence of liver angiosarcoma m vinyl chloride iVCi workers. Experi mental studies, case histones, and epidemiologic studies all suggest VC acts as a lung irritant. Thrs literature is bnerly sum marized. Pattv. Yant and Waite* exposed guinea pigs for 30 minutes to 10-40% VC. The principle gross pathological efiect was congestion and edema ot the lungs, and hyperemia of the kidnevs and lungs. Exposure to 10% VC resulted m slight signs of iung hyperemia while hemorrhages, edema, and severe damage to the tracheal epithelium were observed at the higher concentrations m animals dvmg from the initial exposure. Pulmonarv congestion was present after two weeks m surviving animals. Lower exposures for longer time periods 150-500 ppm tor six months) resulted in no change m lung weight m rats, guinea pigs, rabbits and dogs. Expo sures at concentrations greater than 100 ppm produced reversible liver miurv in the more sensitive species." Lester, et al8 exposed rats to 20.000 ppm !2% VC1 for three months, and 50.000 ppm .5% VCt for 19 davs. They observed increases m liver weight and decreases in white blood cells, but concluded that the observed Ttbto 9. -- Acuta Effiett (Maan % Chanp't in Cftamieai. Plastic* and Rubber Worten by Smoking Cat*forto*. Th# DypotNSf* at* that Pf Should flat differ tifntficantty from tore <H:APF = 0). Tht orw-iiMd t tait was ned la tett lifnifkance. Standard daviatioR u in paranthaife. Currant Jth Woman Pmtia htta M MSt SI NS s NS s NS s 1 Am A FVC ** 3 1 S3 (7 55) 14 i Si" 12 54) <20 0.191 0.336 12 45) 1 <-0 41 0.15) 4 3 52 SS?t + 109 031) 2.03* 11 54) 17 *0.54 14 M) IQ 3 33" 14 31) 0 72 0 34) 2 75** (3 02) 71 *0 28 0.73 <4 15) 0 53) 71 2SC'** l 44* G69 a 74) A PET to 0 97 9 40) 421' 9 701 -ZJ9 19 59) 405 9 731 3429 731 5 70 11! 73) 153 19 10! 472" 19 Ml A FEFlS ?S w 0 40 917) 10 06- -- >5 in 1 93 9 551 4 53 '9 40 -02$ 1)0 08) 9 72** (1 i 681 0J6 S 551 9 15"" 9 47) AFEF29 to 1 63 (6 83) 9 43"" 14 87) l 85 9 60) 100 1J4 99) 0 62 17 56) 430" u: -;:3 ; s;: 7 82"" (9271 A FEFM to 0 93 (12 43) 12!"" i6 25i 0 53 (6 7BJ 11 23 (!??'.( . 32 (13 99) 4 75 ; 44 (1! 831 4*7"" <10 76) A FIF7* to 2 77 (15 42) 14 75-" (13461 4 24 128 851 22 76 .'76 831 5 76 (23 93) 1926" 27 :* iA (23 05: 17 (18 43) ACY/VCt to 14 20 (32 95* *151 14$ 191 u 35 (25 26) -1$ ij* i: 82) 0 55 (29 51) 1 89 (22 4Q| : 34 (28 'li -7 39 (37 33) *o * DOS "u * < 0 023 "# s 0 004 * < 0005 t*6 = ncwiwcne uraw m * of* pne** IS = *ng** 2 = ` po*<tM n" Main wmm * nrtamwta a* tit ten sort CVVC * llaan % ctwn * Wbr ot P Htn n Pf . mam F < to Mot no Pf 2 a i*** nan na Dttor* nn CV/VC ms 666 Occupational and Nonoccupationa) Factors on the Respiratiyy System of VC Workers/Gamble et al RSV 000164? lung edema and congestion could nor he attributed to the irntaftrig effects of VC, and the pneumonia observed was prnbablv due to secondary infection. Keubfer10 exposed rats. mice, and guinea pigs to 5.000.15,000 and 25.000 ppm VC tor 2-hours a day for 100 days without observing any histological damage. In a report of a case of VC gassing in a plant m Creat Britain, a worker washing out a pofvmerization vessel with water collapsed and was given artifi cial respiratory. Subsequent svmptoms included chest tightness.'* Boytsov* reports (without giving the number of species or animals, length or amount of exposure' that inhalation and intra tracheal administration of PVC resin produced a "development of peribronchitis in the lungs'* and local thickening of interalveolar septa. Two studies of PVC workers m Russia and Germany con clude that the respiratorv svstem was affected." w A "consider able number" of % PVC workers m Russia had a "changed bron* chovascuiar pattern and increased pulmonary ventilation at rest"." Eight of thirteen Cerman PVC workers employed for 1.75 to 18 years showed partial pulmonary insufficiency with signs of predominantly restrictive changes of the lungs This latter finding is in agreement with the case described bv Szende. et al.'* A 31 year old male had shoveled PVC dust m a dratty place for 1-vear prior to being examined for severe dyspnea. The possibility of pneumoconiosis elicited bv inhalation of PVC resin was suggested. There are a number of problems with the experimental studies of animals. Only at very high VC concentrations are effects ob served. and these are anatomical changes from gross pathology or histology. More sensitive functional measurements at lower, more realistic. VC exposure concentrations have not been reported. The foreign studies are ontv suggestive, and do not provide enough information to evaluate. There is onlv one reported epidemiologic study of VC and PVC workers in the U 5.14 Cough and sputum production lor most ot 1year or more clinical signs of emphysema were reported m 31'". of the 348 currently and previously employed VC and PVC workers Smokers and nonsmokers over 40 years of age had similar rates ot flow impairment. In the age group under 40 however, smokers had about twice the prevalence of flow impairment as nonsmokers. The higher prevalence of flow impairment in smokers compared to nonsmokers converged slightly with increasing duration of exposure: nonsmokers and smokers with more than 20 years exposure had the same prevalence of flow impairment. The authors conclude that the etiologic agents producing the reduced air flow in workers over 40 years of age or with > 20 years expo sure is unclear but is not due to smoking. Exposure was to VC monomer. PVC resin dust and pollution m a heavily industrialized city. The effect of smoking on respiratory symptoms has become common knowledge following the report of the Surgeon General on the Health Consequences of Smoking H%4) and its sub sequent supplements.'7 The results of this study confirm these re ports. with the possible exception that light smokers (clpack/day) m this study resembled exsmokers more than heavier smokers ( 1 pack/day). Pipe or cigar smokers have been less studied, although it has been suggested that pipe smokers are to be distinguished from cigar smokers.1* Because of small num bers this has not always been done, and in this study these smokers were combined. They generally resembled light smokers and exsmokers in both symptoms and lung function. The effects of smoking on symptoms have generally shown cough and phlegm to be higher in smokers, with prevalence relat- PlUlMto The SMy IMP towton Smetos Comunty (ten yrjfi** ftowaan Sffldwi RMon Smelt. toes totalN h> towtoi Sran Slrtfita Sjnva Mustrtal tan a Enfwe* NoMmctos Smear* 0Whitt. N IWWBMH ' Mrrirxt me Post*TM* hwifi Smear* KYC Timm WanrH towoirt Smehrt GrtW 2. 3 4 IWtewu ta* 3 a* t n mm in IGr*M 2 a* 3 ftwttowi 10Tib* . -- Ccmpiriwa ( Rntottonr Symptom Prevalence. ft Clip niftta Nmmat % ft Catch & PM*" ft 531 34.9 192 in 56 63 292 21 6 26 4 92 28 13? 1C? 154 111 513 *7.2 462 HO 363 75 10.7 16.5 17? 401 162 '3 170 96 SS! -- -- m 5i 1 n 70 13 1 2667 27 0 269 1012 64 3715 235 95 23 7 90 *3 * 15 *0 19 C 26 152 Journal of Occupational Metficme/Vol. 18. No 10/OctOber 1976 *Wtow ft 212* 111* 26 5* sot 10 7* 781 1801 51 69 22 67 21 fit >43 124t 233 667 RSV 0001648 I J to the amount ot smoking, a relationsmp supported by this study- Breathlessness, while generally higher m smokers, is olten not related to the amount of smoking. This is hypothesized as duo to selective reduction of smoking in those developing symptoms of breathlessness, a more severe and disabling condition than "smokers cough" " Although movement of less fit heavy smokers into lighter smoking or nonsmoking categories seems a plausible explanation, selection does not appear to be a strong factor m this population as there was a high prevalence of breathlessness cn the heavy smoker category. A trend for breathlessness to increase with increasing age is commonly observed." and was apparent in this study. The association of cough and phlegm with increasing age has not been as consistent. Some studies report an increase with age:" 10 others (including this study' find little tendency for cough and phlegm to increase with age " 2' Two studies m West Virginia have observed an association be tween educational level and prevalence of respiratory symptoms and ventilatory lung function capacity with the lower prevalence of symptoms partly attributed to (ewer smokers in the higher educational categories " JJ Stebbmgs1' m 469 white male non- smokers found no effect of social class (based on occupation, education, and incomei on most respiratory symptoms: only dyspnea was significantly less common in the upper social class. Lower pulmonary function was also associated with lower socio economic status in these nonsmoking males.1' Salaried chemical workers in this study resemble the upper social class in that they smoke less than hourly workers, and are probably more educated. Exposure to VC and PVC resin is generally less than that of the hourly workers. It is not known from this study whether social class, exposure, smoking, or some combination of these factors can explain the lower symptom rates or salaried cnemical workers when compared to hourly workers. The same argument applies to the slightly better pulmonary function of salaried chemical workers compared to hourly workers. Among hourly workers, no consistent or convincing differences in respiratory symptoms or function were observed. When workers were divided into exposure categories of work ing only in plastics or chemicals, the respiratory svmptom rate was reduced considerably. Workers with more 10b mobility were less healthy in the sense that they reported more symptoms. This could be due to a greater susceptibilitv to having a more unfavor able job experience in terms of exposure to seif-propelled moveme**: to less symptom producing fobs, or some combination of these factors. Although the reasons are unknown, the fact remains that the less mobile "pure" exposure grouos had lower sv~ptom rates than control rubber workers, maintenance, and the mixed exposure workers. Are the svmQtom rates observed m this population comparable to those m other populations' Table 10 compares the prevalence of resoiratorv symptoms m this study with other studies. There i$ considerable variation between reoorted symptoms in the various populations. The workers in this study compare favorably except for perhaps breathlessness. The effects of age and smoking on pulmonarv function ob served in this peculation are comparable to otner reported studies There were no stgmticant statistical differences m the in tercepts ot the smnkinii 'egression equations Heavier smokers m this cross-sectional analysis had significantly greater reductions o' FEV FEF:s-:v FEFso and FEFt with increasing age Two points are of interest with regard to the effect of smoking Before the age of 40. smoking had no apparent effect on pulmonarv function Secondly, 'ight smokers were obvouslv less affected than modor:ie and heavv smokers In the analysis of smoking, one yhouid pi- nine this dose response relation, and not arbitrarily lump to gether all smokers. Careful consideration of possible smoking-eiposure interactions is also required. For example, m a group of workers exposed to asbestos dust, smokers reported worse lung function than nonsmokers when a single regression was used for height and age ad justment." The inference was that smoking increased the effect of dust exposure. Using only a single regression equation tor stan dardization *s misleading however, as smokers pulmonary function decreases more rapidly than exsmokers and nonsmokers Rossiter and Weil" point out that an apparent synergism between dust and age may instead be a smoking-age interaction. When separate regression equations were used for standardization, t.e., one each for nonsmokers, exsmokers, and smokers, they observed no dif ference m pulmonary function related to dust exposure in fact, the asbestos dust exposure had a more detrimental effect on nonsmokers than smokers. We know there was a smoking-age inter action m this study. Since we are primarily interested in the effect of VC exposure on pulmonary function, age and smoking ad justments were made using the regression equations of the various smoking categories iFigs 1-6). As there was no difference m pulmonary function between current job categories. Mid no nonexposed group of workers was available, the regression equations used for standardization were derived from the smoking cate gories of the total population. After standardization, increasing duration of exposure in chemi cals. plastics, and rubber was not associated with large changes m pulmonarv function. Reductions in FEF*s, the most sensitive mea sure of small airways obstruction was consistently and significant ly associated with working m rubber: less significant reductions m FEFrs were associated with hourly chemical and plastics workers, and FVC in hourly chemical workers. Other pulmonarv function parameters generally remained the same or improved with in creasing duration m chemicals or plastics, and with increasing cumulative VC exposure The reported case of pneumoconiosis on exposure to PVC resin'' ts suggestive that high exposure to PVC resm mav esult m a restrictive tvpe of respiratory disease Baggers in the chemical plant are exposed to from 1-5 mg.m1 of particulate (measured bv area Hi-volume samplers:: respiratory particulate is l.'tO to 1 20 these levels. Exposure to the PVC resin m plastics appears higher for Banbury operators but lower for workers m milling, and negligible tor other plastics worke'S The low prevalence oi FVC moairment m both chemical and plastics workers does not supoort the Hvpothesis of PVC resin exoosure producing volume restriction What difference is tnere oe'ween the workers m this studv and those reported on b\ Miller et a > Pjimonarv 'unction impairment tor FEV TVC. FVC a-crEr---FVC n this studv emploved the same definition as Mille' et a * .n their studv or VC-PVC workers The prevalence of imparmert 'or FF:t -s. using the same criteria, was essentially zero, and thus tar below the 53% thev observed 'he Cutohs for impaireo now as measured ov FEFso,FVC and FEF--, CVC have been shown to oe reasonap'v elective in distinguishing nor mal subiects from those with obstructive iung disease ' The high est prevalence almost 30% of impai-ment was tor FEF* FVC and supDorts the observed ass-xidlion or -educed FF-s with increas ing duration o' work All VC-PVC nonsmokers less than JO vears oi age. and all worker m this studv less than 40 vears ot age had about a 20% prevalence of impairment for FEV FVC and FEF-S.TVC The prevalence of impairment increased tor non 668 Occupational Nonoccuoationai Factors on the Respirator* System of VC Worhers/Gampie et ai RSV 0001649 smokers over 40 in both populations, but more so m the Miller study- The rates of flow impairment in both studies are the same for smokers over 40. In both studies the prevalence of rmpaired FVC < < 10%) is considerably lower for flow impairment 118-75%) and much lower than expected from exposure to asbestos." The association of increased pulmonary function performance with increasing exposure and work duration, particularly m chemi cals. suggests that selection is occurring in this population. The reason for the lack of association between VC exposure and respiratory effects may be due to differential migration of more susceptible workers out of chemicals. Note that the mixed expo sure group reported a higher symptom rate than chemical and rubber workers who had never moved. The current plastics worker had symptom rates comparable to or higher than this mixed expo sure group, suggesting that net migration oi ''susceptible*'' may have been into plastics The association of smalt airways ob struction with exposure mav be more informative than symptoms because (1) small airways may be more sensitive to the effects of environmental agents: and (2) small airways obstruction is probably not noticed by the individual to the same extent as symptoms and FEV reductions, and would therefore not be af fected as much by selective migration. Several conclusions emerge concerning factors that affect base line pulmonary function in this population: >1) age and smoking were the two most important factors reducing pulmonary func tion; smoking was associated with obstruction only (no significant effect on FVC). 12) small airways function as measured by FEFrs was affected by both smoking and work exposure, primarily rub ber worker exposure. (3) work, whether measured by duration or estimated cumulative exposure to VC and after adjustment for smoking effects, was not associated with reduced baseline pulmonary function (except for FEFrs), (4) although prevalence rates of impairment are not often reported, the air flow im pairment (FEV^FVC. FEFrsl. rates appeared elevated only in the older smoker. Respiratory symptoms and measurement of pulmonary function are two somewhat independent and yet overlapping methods for investigating the risk of environmental exposures to the respira tory system. Symptomatology suffers from the disadvantage of be ing subiective. can show interobserver variation, and requires adequate recall on the part of the person being interviewed: symptomatology is useful m diagnosis, particularly chronic bron chitis. Indeoendent validation of svmptorm in practice turns out to be pulmonary function measures, despite the fact that different, albeit overlapping, parameters are being measured. The observed association of reduced pulmonary function with increasing seventy of symptoms increased the vaiiditv of respiratory symp tom information The conclusion that VC exposure did riot consti tute a significant respiratorv hazard m this population was strengthened by similar results for both svmptoms and pulmonary function. While one methodologic strength of this present study is the ability to make internal comparisons between work groups, it must be stressed that none of the groups can be regarded as hav ing worked tn haiard-free conditions. 8oth rubber and plastics workers are exposed to varied levels of dust and fume and it could be that reduction m lung function among chemicals workers (whether due to vmvl chloride exposure, or (o some other agent* are being obscured because of similar reductions m the other |ob groups The results of FEF-vFVC impairment (pertaining to that part of the respiratory tract thought to be first affected bv harmful exposure -- the small bronchioles! suggest increased abnormality Journal of Qauoational Medicme/Vol. 18. No 10/October 1976 rates in ill workers. Indeed, for several of the pulmonary function tests the chemical workers had better results than rubber and plastics workers. To assess the potential resprratory hazard of eac h exposure category, befrwe-and-after shift tests were earned out on some workers. Any reduction m respiratory function over the shitt suggests the likelihood of some harmful exposure m the working environment." Smokers overall had statistically significant reductions for all ventilatory tests: nonsmokers showed little reduction. The most obvious reductions were flow rates at low lung volumes, i.e.. mea sures of small airways performance. Chemical workers who were smokers had significant reductions for five of the seven tests, pre dominantly reflecting small airways obstructive change: both plastics and rubber workers who smoked showed reductions of similar magnitude No clear picture emerges suggesting one |ob group faced greater daily respiratory insult than the others. Re duction in small airways performance among nonsmokers in each job group suggests that all workers were exposed to agents with adverse respiratory effects. In a clear environment the average re sult for these nonsmokers would have been a slight increase m test performance. Whether these acute reversible changes have anv permanent effect is not known. The significance of these findings is unclear. The small airways obstruction associated with work in the rubber division, i.e.. the control group, could be related to a number of environmental agents. The complexity of the industry and the heterogeneity of the control group does not allow for determining the etiologic agents. The rubber worker group was selected on the basis oi lower particulate exposure and never hav ing worked in chemical or plastics. But they could have, and probably did. work in other jobs with higher exposures wrthin the rubber division. A complete work historv for each rubber worker would be required to investigate further the association oi re duced small airwavs function with work in ruboer. Fundamental and more difficult questions remain. What is the biological significance of acute reversible reductions in small air ways function over a shift? What is the biological significance of statistically significant reductions in baseline pulmonary function over a longer time period? For FEF?s, the reduction is on the order of -1%/vear Over a 40 vear period, this would amount to a 40''.'# decrease. However, some individuals have a reversible change of 40% m the course of a dav. The association of working in rubber with a downward slope or the percent predicted FEF-s is a finding that requires further investigation of workers in other areas oi the rubber plant, an investigation currently underway. "he amhoo thank Mie ' id**# nr Mammal matte's mOSh rousum Hrtwn-s'S <'* a^v-vancf >n ae'-s.-e -ip VC escrvjre source Mars ,ane Th i<m manuvrnot oreDaritnn anC union dOO enmoanv ort-cas If* the* assistance in the prniect References 1 Pattv FA indutt'iai Sons New vork. and To*coiOv. VqI 2. lohn Wilev and 2. 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Williams T. and Battigelli MC Respiratory function and symptoms: An environmerual-epidemioiogic studv of rutiber workers exposed to a phenol-formaldehvde tvpe resin Amer Ind Hvg Assoc I 37 1976. Correction In "UV Keratoconiunctivitis Vs. Established Dose Effect Relationships." IOV Aug 1976. p. 573. the term "Amp" was erroneously used with reference to emission characteristics of lamp. LVhe'ever "Amp" appears. ( was intended to read "Angstrom Units." 670 Occupational and Nonoccupational factors on the Respiratory System of VC Workers/Gamble e; at RSV 0001651