Document 1gda1qYR0NvDeq8NwGVpB3yNj

;;.W" . T' s . I *- * ------- . 1'I'cvaleuce of cliseaso among vinyl eh Lorlde an cl polyvinyl chloride workers by Until Lilis, M.D., Henry Anderson, M.D,, V.'iilian J. 1* ieholson, Ph.D. Susan Uaum, M.l). , A If S. Ki.sclibeiu, M.l). a;ul Irving J. S::"l ikoff, M.U, / The emergence in January 1074, of vinyl chloride as a now occupational carcinogen, producing hemar.giosarcoma of the livor, focused new and nuch greater attention on the toxicologic effects of this chlorinated hydro carbon. A considerable number of studies had been published on the rather puz zling and unique syndrome of "acroosteolysis" (Table 1) mainly describ ing the bone lesions in the distal phalanges of the fingers, but also the associated scleroderma-like skin lesions and the striking vascular (arterial and arteriolar) changes, pathologically the main lesion, leading to secondary bone and skin changes (Tables 2 and 3). Much less attention had been given to the hepatotoxic effects of vinyl chloride, although' convincing experimental evidence had been produced (Torkelson et al., 1961) and scattered reports of ill-defined liver changes were reported in some 'studies of vinyl chloride exposed workers (Table 4). i There was evidence that liver damage occurred in workers exposed to higher levels of vinyl chloride. In some studies the liver changes (hepatomegaly, tenderness on palpation, abnormal liver tests) were* found to'be reversible afttvr cessation of exposure. On the other hand, some observations mentioned the progressive nature of liie liver changer., when toxic exposure continued, to what was stated to be "chronic hepatitis' Recent work from Germany (Marsteller ct al., 1973) reporting a detailed study of 20 PVC workers, brought a very important contribution to cur present knowledge on the liver changes induced by this toxic exposure. The authors were alerted to the problem by the occurrence of upper gastrointestinal bleeding in several workers of a PVC producing plant. Ksophageal varices, splenomegaly, hepatomegaly, fibrosis of the liver capsule (by laparoscopy), delay in the excretion of bro.r.rutlphale in t thrombocytopenia,were the most prominent findings. The pathological changes encompassed collagenous transformation of the liver sinusoids, focal activation of Kupffer cells, increased collagen deposition in the portal spaces, portal fibrosis, septal and intralobular fibrosis. * There were a few reports in the literature of lung; changes in l'*VC workers.. One case of pneumonconiosis in a thirty year old worker who had inhaled PVC dust was reported. The lung biopsy showed granulomatous lesion:.(foreign body type) to be present, l'ibrotic changer, and alto rod' pul monary function tests wen: reported in 96 workers exposed to poi\vinyl chloride dust; the changes wore core pronounced in perrons- with long oiposuro (Vortkin et al. 1970). 100082 ' Current Investigation In tlift available i'-taratarc on vinyl chloride and polyvinyl chloride ad verse health effects th=re wore no nccr.va tc data on the prevalence c.; disease ii*. exposed workers, tins relative pro.' a vunce o 1 the va ri oa_. logic charges, their possible association and Lin;e sequence. V-e hava undertaken clinical sIndies or a number o i croups of vinyl chlo ride exposed workers in order to assess the prevalence ol vinyl chloride induced chen5.es and to define the natural history of this occupational disease. V/e are reporting the results of a purvey' (March 1974) of 2(37 workers currently employed in a VC polymerisation plant, including; vir tually the entire current production workforce. 37 former workers ware examined as well. In both groups, exposure for some had started in 1946, when the plant opened, y. Altogether 354 men were examined. Table 5 shov/s the duration of exposure for the group and Table 6 the age distribution of the oen. More than half were under 40 years, 20% v/ere 51 or older. METHODS The medical ' .` w. -- ' examination included : detailed occupational ; * history, `past medi cal history, physical examination with special attention to the skin, hands and feet, arteries accessible to palpation, liver and spleen. An Allen test for the assessmentkoE the peripheral cii-culation in the areas supplied by the radial and ulnar arteries was performed. Each examined worker also had the following: X-rays of the chest, hands and feet;' pulmonary '.function tests; complete blood coll counts including platelets; blood chemistries including bilirubin, SCOT, KGPT, LBft, alkaline phosphatase, total protein, electrophoresis of serum proteins, fibrinogen split products; alpha fetoprotein, antinuclear antibodies, > antir.iit.rchondr.ial antibodies, ruet'.smooth muscle antibodies Australia antigen E by ??d ioii .cunonssay and liver antibodies. Urinalysis, including ni.ovose.opLc cxcminalion of lhe sediment, ves done. All exanint-.! workers were also tested For'.carcino genic embryonic antigen. In a limited number,, studies for chromosp.r.v breaks in circulating lymphocyte;; wore undertaken. RESULTS Unfortunately, appropriate VC 1 wcsurm.nnt;; had not been iw.de in the past. l.'c; have findings which suggest, however (Tabic; 7), that VC levels nay have been, considerable at times, suflicion t to produce symptoms c:l acute overexposere; tor cxa.mple, 14 of the 351 workers Juid had loss of consciousness a l one l uu; or another. i-n any case, our data fad ionic Lhal measured levels Would be of liiaildd utility, unless integrated over time, since; both total exposure and duintion from, onset of exposure soem to be; of importance* in relation lo likelihood of abnormality. The influence of (hose vniinbles >->uy be demonstrnted ;in ; number ol area-:. 100083 This v.du so i.nsolur 'ribnomaL pcrlphc vo 1 oi rcu Il. iou was ooiK.a i n._:d (Table S) . 3 Auabness and ting L ir.;.: ol the l ir.;;cit,, aloiijf with .i ncrcw;;"f; i.rnsi L Lvi ty Lo cold, were early symptoms, They v/erc often associated vLlh ]i:i i n and cyanotic clir.colorati.oii some t imes also .involving tlie toe:.. Classi cal Raynaud's syndrome, charm; tori xed by cold-induced, narked, sudden, and sharply demarcated pallor of the lingers lolloped by cyanotic dis coloration in the sane area', was only found in 3,G% ol the cases. In general, the effect of vinyl chloride exposure on the peripheral ves sels of hands and ieet appears to produce a wider range of symptoms than those characteristic of Raynaud's syndrome. As noted, the prevalence of these changes rose with duration of ex posure. Typical Raynaud's syndrome was found in almost 10% of cases with more than 20 years of exposure. The prevalence of Raynaud's syndrome was significantly higher in workers v/itli more than 10 years of exposure, than in those with less than 10 years exposure. Symptoms of abnormal peripheral circulation (Table 9) were more frequent in workers currently exposed than in those with past exposure. An abnormal Allen test indicating delayed arterial circulation in the areas supplied by the ulnar and/or radial arteries, was found in 94 (26.6%) of the examined workers (Table 10). The percentage of persons with abnormal Allen tests inci*eased with their length of exposure. The prevalence of an abnormal Allen test in workers v/itli more than 5 years exposure wasTrIgn l r i c a rfi 1 y rTgTnn' than in those with less than 5 years exposure. ~ Pseudo-clubbing of the fingers was also found with increasing fre quency as the duration of employment increased; the overall preva lence was 8.7%; in the group with more than 20 years pf exposure y it was 17.3% (Table 11). However the difference in the prevalence of pseudo-clubbing between workers with less and more than 3 years of exposure did not quite reach the level of statistical signifi cance. (X^ = 3.G02) Pseudo-clubbing was almost always associated with signs and/or symptoms of abnormal peripheral circulation, and was a more frequent finding than typical Raynaud's syndrome. In some cases, especially in persons with past exposure, there was a history of Raynaud's syndrome which had gradually faded, while psoudoclubbing had persisted or even progressed. Skin changes (Table 12) involving the fingers, hands, forearms and some times face, wore found in 23 examined workers. The fingers and hands ap peared to be slightly edamatous, the skin was thickened, tense and st.iN, with decreased elasticity and sparse folding. V/el 1 circumscrLI.ad plaque or band areas of sclerodennn-likc skin changes, as described by others, were not found. In 9 of the 23 cases in which skin change*; were found, Raynaud's syndror.e was also px-csent. Pain in the small joints of the fingers and hands (Table 13), was a complaint in 28 (8%) of cases and was found mainly in workers with current exposure, oven of short duration (Table 14). There v.as no special trend regard ing pain in other joints, except for the wrists, where nosl oC the cases were found in workers with norc them b years oi exposure. There were no symptoms suggesting involvement of I he sacroiliac joinl.;, and no radiologic evaluation was undertaken. 100084 Done ch;in;e.-. in the distal ph.ii utiles ol riug.r;; nmi l.o;.-.'1. will bo a Lely reported in detail. V.hiie slight charges, seed as r> irgir.ul cortical defects and elLghl tuft rcsorbfion were: not uncommon, transverse detect;-- and fractures were found in only 4 cases. We wore i.ntei-os tod in the possibility that hyper teii5:ion (Table 15) might bo of importance. V.e did not find this to be so, Th.e overall I prevalence of hypertension (as defined by V/ItO critci'in) was 12',',. There war. no correlation with peripheral vascular iinpaJ nnent in the* hands and feet. Abnormal urinary findings were not prominent either (Table 16) . The liver was found to he slightly ox* moderately enlarged in 15% of the cases (1 to 2 finger breadth below the right costal margin; 11 to 13cm vertical span (Table 17); this finding was more frequent in workers with longer duration of expesux-e. Only in one case was the liver found to be markedly enlarged. The inferior pole of the spleen was palpable in 12 (3.4%) of cases: Again, only one person had marked splenomegaly. There was a highly significant difference in the prevalence of enlai-ged liver in workers with more than 5 yeax~s exposure as compared with those with shorter exposux-e. The same comparison for splenomegaly did not show a statistically significant difference. According to the past medical history, a diagnosis of cirrhosis oE the liver had been made previously in 5 cases. Esophageal varices had been diagnosed in one patient who had undergone surgei'y, including portocaval shunt, 12 years before the present examination, with good clinical result. Abnormal liver function tests (Table IS) were found in small percentages (6% for bilirubin and SCOT, 9% for SGPT), except for alkaline phosphatase which was elevated in 59 (16.6%) of cases). Duration of exposure correlated with an increase in the prevalence of elevated' alkaline phosphatase, especially in workers with more than 5 years of exposure. Thoi-e was a higher percentage of abnormal liver tests in workers with current exposure than in those with past exposure (Table 19). Alkaline phosphatase war. an exception, since similar proportions of abnormal tests were found in persons with current or prior exposure. The best correlation between clinical findings of hepatomegaly and/or splenomegaly and abnormal liver function tests was found to be that with elevated alkaline, phosphatase (Table TO) ; -11% of those with such clinical abnormalities had increased alk.iiine phosphatase. Hematologic abnoxT.'.alities wore scant in our study, Thrombocytopenia, a frequent finding in the German studies, was present in only one of the examined voikors (Table 21) . The possible contributory effect of significant ethanol intake was care fully considered (Table 22): no trend as related to duration of^exposure could be found for ethanol inlake. In ono-third of the cases with clinical liver and/or spleen changes sig nificant ethanol intake could have been a factor (Tabic 23) ; and in 251-.< , of the cases with iucx'cased alkaline phosphatase was there a,history of significant intate (Table JM). Further, the lircvalcnce of an enlarged 100085 liver niul/or spleen in, por:'On<; with and without i gni I i c;-.;! t o l. i 1 r J j,ni;i!,-. wan compare'.! (Table 25) . V/hilc there* was no statistically 5- ign fiencJ. dif L'erence in workerr; v/itli less than 10 years of exposure, in ihone .iLk more than 10 year/; exposure, there was a higher prevalence of on! urged liver and/or spleen in persons with a significant ethanol in fake. A Multiple factor additive interaction may bo considered. LivCr function tests were also analyzed in relation to elknno'l. intake (Table 26). There v.es no significantly hi giiev prevalence o el created alkaline phosphatase, bilirubin or LDIl in the group with significant ethanol intake. However, high SGOT or GOV'T values \/orn notably more frequent in this group. It is of interest that elevated alkaline phosphatase, the most frequent biochemical abnormality found, did not correlate v/ith ethgmol intake, while there was a significant correlation with duration of vinyl chloride exposure. ' Many of the examined workers (Table 27) gave a past medical history of "gastritis," ulcer (gastric and duodenal), upper gastrointestinal bleed ing (most often attributed to ulcer) and gallbladder disease. However, it is difficult to know whether such symptoms v/ero more common than might be-expected in a similar group without YC exposure. * Out of the 112 workers with such past medical history, there were 28 (2 57) -'ho were found to have enlarged liver and/or spleen (Table. 28) * the percent age was 38% for those with past upper gastrointestinal bleeding and 38.47> for those with a history of gallbladder disease. In the other 242 workers without such a past medical history, 29 (12%) were found to have an en larged liver and/or spleen. Chest x-rays of 142 examined workers were available at the time that this report wds prepared. In some of the cases linear reticular and less often nodular changes were found in the middle and lower lung field-' (Table 29) . No relationship was observed with smoking or chronic bronchitis (Tables 30 and 31). The significance of these changes is difficult to evaluate at this point since most of the workers had been exposed to particulate polyvinyl chloride resin as well as to vinyl chloride. Three of those 4 with abnormal chest x-ray findings had had previous dust exposure (in coal mines for periods ranging from 4 to 0 years). There was no relation ship between chest x-ray changes and liver changes, but signs and 5:y-.~clows of peripheral vascular impairment (Raynaud's syndrome, cyanosis, pscccb-- clubbing, positivo-Allen test) (Table 32) were found in more'than h.al f (53%) of cases v/ith abnormal chest x-ray findings. The prevalence of Raynaud's syndrome was significantly higher in the group with abnormal chest x-rays. ' _______ Discussion and Cone!unions Our findings confilm the broad outlines of the clinical syndromes rcporled by other investigators. In the examined group x*clativcly high VC exposure had occurred in the past, and symptoms of acute prcnarcotic effects were reported by more than half of the examined workers. 100086 Cl Lnieal 'nd symptoms ol abnormal p1-- i J.in.: V-'l l r.'l ! Lon in 1 ho fingcrs and to os wore quite free non t., with cyiino.iin p v : > 1 a 12 per cent, excessive .sensitivity lo cold in lf> rorr-c !. am! ?ui .b and tingling of the C.'ugers in 24 percent of cases, A typical Kaynnud'r; syndrome was present in 5.7') of cases. An abac r.ia! Alien intlic in;' delayed or ter ini circuln t i on in the awns ?: p<iIj.on by fi:e ulnar nr.J/or radial arteries was found in Di (25. C'o) of tha o.-aiMinad workers, The prevalence of all these abnormalities iner a red w i tl; J aii;: th of VC exposure. Hepatomegaly was a finding in 15% of the examined workers, while splenoi.iegaly was found in 3.4%. Cirrhosis of the liver had been previously diagnosed in 3 workers, and, in one, esophageal varices wi th upper gar, fro intestinal bleeding had led to surgery including portocaval shunt. Alkaline phosphatase was the test which was most frequently found to be abnormal and showed the best correlation with clinical findings. Hepatomegaly and elevated alkaline phosphatase were significantly more frequent in workers with longer VC exposure. Radiologic pulmonary changes, linear reticular and nodular opacities in the lower and middle lung fields were found in a number of cases; the prevalence of these changes was higher with longer duration of exposure, and there was a significant association with peripheral-circulation abnormalities. The evaluation of these pulmonary changes is still in progress. , x , Our results indicate that liver involvement and probably lung involve ment in PVC workers are significant and should be given full attention in the medical surveillance of workers with past exposure. Rutux'o exposure to vinyl chloride should bo controlled in osclor to pre vent development of all adverse effects, including tho carcinogenic effect. 100087 7 Table 1 Aoroosteolysis 1957 Filatova and Gronsberg 1963 Sxiciu et al 1966 Cordier 1967 Harris and Adams 1967 Wilson ot al 1971 vDinman ct al 1972 Markowitz et al 1972 Juhe et al 1973 Misgeld ft al "Angioneurosis of spastic character" - Raynaud's syndrome - (hands and feet) 6% of 168 exposed workers - Scleroderma-like skin changes - (hands, feet, face, neck, thorax) 3.6% of examined - Raynaud's syndrome - Scleroderma-like skin changes , - Lytic lesions of terminal phalanges in hands and feet - The same changes and -'pseudoclubbing of fingers - Involvement of sacro-iliacjoints and patella Skin biopsy and pathology data Arteriography Occlusion of interosseous arteries < Arteriography -->* spastic arteries visualized only after Priscol 100088 Acroosteolysis Bone Changes Marginal and/or cortical defects in distal phalanges Loss of cortex iu tufts of the distal phalanges "Half-noon*1 defects or cuts Transverse defects or fractui'es Complete resorption of tufts and part of sha-fts Involvement of the larger bones Cystic lesions and. increased radiolucency (ulna, radius, huirierus, os calcis, patella) Erosive aiul sclerotic changes in sacro-iliac joints 100089 Table ;< Acroostoolysis Skin biopsy pathology* * - Thickening of demis - Nonfibrlll ary homogenization of collagen and' thickened collagen bundles l - Disorganization of clastic fibers, which are split and broken * - Inflammatory infiltrates, predominantly peri vascular (lymphocytes, few histiocytes) - Thickening of the media of dermal arterioles - Uneven endothelial thickening - Marked swelling of dermal nerve fibers vacuolization of rixoncs - Ir.torsit.ital edema - Dilatation of lymphatics 100090 Evidence of liver damage in PVC exposed workers 1949 "Hepatitis-like liver changes" Tribuch ct ai. (USSR) 1953 "Chronic epithelial hepatitis" in 15% of cases; hepatomegaly, in creased bilirubin and prothrombin time, abnormal .TakaLa-Ara test. Pushin (USSR) 1953 Hepatomegaly in 30% of 1GS ex amined workers, splenomegaly (6%). Liver biopsy in 2 cases: "chronic hepatitis." Elicit! et at (Romania) 1967 Hepatomegaly; persistent raised bilirubin. Harris (England*) , 1967 Increased BSP retention, raised icterus index-----------related to degree of exposure. 1972 Pain in RUQ and abnormal liver tests (in 2 out of 7 patients with sclerodcrmn-like skin changes). Jr.he o t al CGavnary) ' 1973 JUa) discomfort; abnormal liver changes. Misgeld' at al (Go.rm.any) 100091 // Table 5 Duration of vinyl chloride exposure among 354 workers in Niagara Falls Duration of exposure (years) Currently employed Formerly employed Total <2 36 25 61 0 2.1-5 62 13 74 3 5S1-10 47 15 63 ! 10.1-20 77 27 . 104, 3 20+ 45 7 52 I a 267 87 354 ' 100092 Table G Age distribution of, 354 vinyl chloride exposed workers (Niagara Falls) Duration of exposure (years) <2 2.1-5 5.1-10 10.1-20 20+ Total 21-30 39 45 17 0 0 101 31-40 9 17 18 50 4 93 41-50 8 9 24 30 14 G5 51-60 4. 1 3 21 27 5G 60+ Total 1 61 3 75 0 62 3 104 7 52 14 ` 354 n W "Jl_!i; Ijfj,.-3 iflWSWIBW Table 7 Symplons of acute overexposure among 354 vinyl chloride workers i 10009 Table 8 v . Clinical signs and symptoms of abnormal peripheral circulation among 354 v^nyl chloride exposed workers Duration of Exposure (years) <2 2.1-5 5.1-10 10.1-20 20.1 Total Number * Numbness Tingling No. % 61 2 (3%) 75 16(21%) 62 11(18%) 104 36(35%) 52 20(38%) Excessive Sensitivity to cold No. % 2 (3%) 11 (15%) 11 (18%) 26 (25%) 13 (18%) Pain No. % Cyanosis No. % 2 (3%) 4 (5%) 4 (5%) 3 (5%) 10 (16%) 11(11%) 10(19%) 19 (18%) 11 (21%) Involvement of toes No. % Raynaud' s'" syndrome No. % 1 (1%) 5 (3%) ii (11%) s (15%) 2(2.6%) 4(6.4%) 9(8, G%) 5(9.6%) Total 354 85(24%) 63 (18%) 28 (8%) 46 (13%) 25 (7%) 20(5,7%) ^Prevalence in workers with more than 10 years exposure significantly higher than in those with less than 10 years exposure. ?2= 5.783 p <0.02 Table 9 Raynaud's Syndrome among 354 vinyl chloride workers Exposure Active Prior Number 267 87 Raynaud 's Number % 17 6.4 3 3.4 354 20 5.6 is \ // 100096 100097 VO N Table 10 ' Abnormal Allen Tost among 304 vinyl cliloriMe workers Duration of Exposure (years) <2 2.1- 5 5.1- 10 10.1-20 20+ Abnormal Test Results ont Exposure Prior Exposure 7/36 11/62 16/47 22/77 12/45 2/25 7/13 7/15 ' 5/27 5/7 Total* ' 9/G1 (14.7%) 18/75 (24.0%) 23/62 (37,1%) 27/104(26.0%) 17/52 (32.7%) Radial - 10 Ulnar - 38 Both - 46 6S/267 (25,5%),. 26/87(29.9%) 94/354(26.6%) *Prevalence of abnormal Allen Test in workers with more than 5 years exposure significantly higher than in those with less than 5 years exposure. y 2 _ ,,,,,, ~ -- 5,0S4 002<p< 0.05 * in* n Table n /> Wrists ?0 No. % L 1 1.6 t 1 1.6 1 3 2.9 1 2.0 r* ' ficant lor more than libbing of fingers amoner 394 vinyl chloride workers f trs) Pseudo-clubbing of fingers Current exposure Past exposure Total 2/36 3/62 -* 3/47 7/77 7/45 2/25 0/13 3/15 2/27 2/7 4/01 (6.5%) 3/75 "(4.0%) 6/62 (9.7%) . 9/104 *(S.6%) 9/52 (17.3%) 31/354 t xi-Sns/symptoms o'f peripheral vascular disease. (S.75%) !typical Raynaud's syndrome. 100098 Table 12 Skin changes in 354 vinyl chloride exposed workers Duration of exposure (years) Total number examined Skin changes Number % < 2" 61 4 6.5 2.1-5 75 2 2.6 .5.1-10 '62 3 4.8 , 10.1-20 104 S 7.7 20+ 52 6 11.5 Total 354 23 Raynaud's syndrome was present in 9 cases. 6.4 100099 100100 Table 15 Duration of exposure (years) <2 2.1-5 5.1-10 10.1-20 20+ * Hypertension among 354 vinyl chloride workers i Hypertension Exposure Systolic Diastolic Systolic and Diastolic 36 Current 25 Prior 62 Current 13 Prior 47 Current 15 Prior 77 Current 27 Prior 45 Current 7 Prior 0 0 1 1 1 .0 3 3 3 0 0 1 0 0 0 1 2 1 5 0 2 2 2 0 2 1 4 2 4 2 Total 2 3 3 1 3 2 9 6 12 2 Total 354 12 10 21- 43 C Note: Workers with hypertension had no greater prevalence o/ peripheral vascular , changes in hands and feet. Elevated BUN present in only three instances. totoot ri a t ' Table 16 Abnormal urine findings among 354 vinyl chloride workers Table 17 Hepatosplenom'bgaly among 354 vinyl chloride workers Duration of exposure (years) Total number examined <2 61 Enlarged liver* No. % 4 6.5 Enlarged spleen*1 No. % 1 1.6 2.1-5 75 5 6.7 2 2.7 5.1-10 62. 7 11.3 2 3.2 10.1-20 104 20 19.0 3 2.9 20+ 52 17 32.7 4 7.7 Total * \ 354 53 15.0 12 3.4 Difference in prevalence of enlarged liver in workers exposed for less than 5 years as compared to those ex posed -for more than 5 years. .2 /v. -- i>U7 p <0.001 2 For enlarged spleen^ = 0.945 ft.s. COTOOT Table 18 3" Or Abnormal LFT among 354 vinyl chloride workers Duration of Total number exposure (years) examined <2 SI Bilirubin >1.1 2 SCOT SGPT >50 >36 "1--" ` 35 LDH >225 0 Aik. Phos. >86 9 12.6% 2.1-5 75 5 47 0 7 9.3% 5.1-10 62 7 354 11 17.7% 10.1-20 104 2 683 19 18.2% 20+ 52 5 461 13 25.0% Total 354 21 ( 6%) 20(6%) 31(9%) S(2.3%) 59 (16.6%.: ^Prevalence of elevated alkaline phosphatase significantly higher in workers with more than 5 years exposure than in those with less than 5 years exposure. ~7(_2= 3.84 p=0,05 100104 Of Table* IS Abnormal LFT among 354 vinyl chloride workers currently or previously employed Liver function test Current employment (267) Bilirubin >1.1 SGOT >50 SCPT >36 LDH >225 Aik. Phos, >36 IS (6.7%) 17 (6.4%) 26 (9.7%) 6 (2.4%) 43 (16.0%) Prior employment (S7) 3 (3.6%) 3 (3.6%) 5 (5.7%) 2 (2.3%) 16 (18.0%) Hcpntosplcnoncgnly, Hepatic tenderness (SG) 6/20 (30,0%) 8/31 (26.9%) -27/59 (45.8%) * S0T00T n) Hr Table 20 Ro.ation of hepato and/or splenomegaly to elevated alkaline phosphatase among 354 vinyl chloride workers Duration of exposure (years) <2 2.1-5 5.1-10 10.1-20 20+ No. 61 75 62 104 52 354 Enlarged liver and/or spleen, or hepatic tenderness 7 ... 7 10 20 20 64 Elevated alkaline phosphatase 3 43% 1 14% 4 40% 10 45% 9 45% 27 41% 90T00T Table 21 ?2 Hematologic changes in 354 vinyl chloride workers i Total number examined Thrombocytopenia <150,000 Lcucopcnia <4,000 4,000-5,000 Hemoglobin <14 gr. 61 18 1 2.1-5 75 36 1 5.1-10 62 12 10.1-20 104 6 4-r too H- Total 52 354 1 1 (0,3%) 6 *5 (1.4%) 28 (7.8%) 2-:-+ S (2.2%) +persons v/ith past history of G,I. bleeding. 1 Table 22 Alcohol intake in 354 vinyl chloride exposed workers Alcohol Intake Duration of exposure (years) Total fuunber examined ++ (1-2 quarts/week) +++ (2-3 quarts/week) 2 5, 61 10 5 -1-+++ Known alcoholic 0 Total % 15 24.6 2.1-5 5.1-10 75 * 62 11 13 4 0 1 16 21.2 0 .13 21 10.1-20 104 9 4 0 13 12.5 20.l-> 52 10 1 1 12 23 Total 354 53 15% 14 3.9% . 2- 0.67/ 69 19.5% 100107 Table 23 Significant alcohol intake and liver changes (clinical) * Duration of exposure (years) i Total number examined Enlarged liver and/or spleen or hepatic tenderness No. % Cases with significant alcohol intake No. % <2 61 7 11.5% 2 3.3% 2.1-5 75 7 9.4% 3 4.0% 5.1-10 62 10 16.0% 4 6.5% 10.1-20 104 21 20'. 0% 4 3.8% 20+ 52 354 20 38.0% 65 18.2% S 15.0% 21 6.2% 100108 SU ^0 3o Table 24 Elevated alkaline phosphatase and significant alcohol intake Duration* of 1 Total exposure (years) 1 examined Alkaline 1 phosphatase No. % Significant alcohol intake No. :% ^2 2.1-5 6.1-10 10.1-20 20+ 61 75 ; 62 - 104 52 9 7 11 19 13 12.6 9.3 17.7 18.2 25 1 1 6 2 4 1.6 1.3 9.7 1.9 7 .7y Total | 354 59 16 14 3.9 100109 100110 Tabic 25 Hepato- and/or splenomegaly and significant alcohol intake <2 Total number examined * 61 Significant alcohol intake Enlarged Total liver and/or number spleen No. % 15 2 13.4% No significant alcohol intake Enlarged Total liver and/or number spleen No. % 46 7 15.0% 2.1-5 5.1-10 75 62 16 . 13 2 12,5% 4 30,5% 59 49 4 6.8% 5 10.2% 10.1-20 104 13 4 30.5% 91 17 187% 20+ 52 12 S 75.0% 40 12 30.0% Total 354 1 69 ...................... i 20 29,0% 2S5 45 16.0% Difference in prevalence of enlarged liver and/or spleen between the group with alcohol intake and those without alcohol intake non-significant for workers with less,than 10 years of exposure. ... 2_ ' Significant for workers with more than 10'years, exposure. ' ?2= 7.248 p< 0,01' Co Table 26 Alcohol intake and abhontial liver function tests Total number examined Significant alcohol intake Non-significant alcohol intake Total G9 285 304 Alkaline phosphatase No, % Eilirubin JSO To 14 20.3% 1 1.4% SCOT Vrt CL SGPT ldf: Kn, % 9 13.0% 11 16.0% 2 2.9% 45 15.8% 59 16.0% A.2= 0.810 n.s. 20 7.0% 21 6.0% X2= 3.087 n.s. 11 3.9% 20 7.6% 6 2.1% 20 6.0% 31 9.0% *.2= 8.790 7V. = 5.537 p <0,01 p <0,01 S 2 * 3% n.s, m Table 27 Gastrointestinal disease (by history) in 354 vinyl chloride fexposed workers * No. % "Gastritis" 47 13 Ulcer (gastric or duodenal) Ulcer and upper G.I. bleeding 3!\ } 52 J ,) Gall bladder disease Total 13 112 3.6 . i Table 28 Gastrointestinal' disease (by history) and enlarged liver and/or spleen (clinical examination) Total number Enlarged liver No. % "Gastritis" 47 8 17.0% Ulcer (gastric cr duodenal) 31 7 22.6% Ulcer and upper G.I. bleeding 21 . - 8 38.0% Gall bladder 13 5 38.4% disease i 100113 U) -c. 100114 Table 29 Chest x-ray abnormal! tieg*atnonr 142 vinyl chloride workers Duration, of Exposure (years) Current Exposure t X- Hay finqinprs Normal <2 2.1-5 5.1-10 10.0-20 20+ Total 13 Current , 6 Prior 32 Current 3 Prior 19 Current 8 Prior 32 Current 5 Prior 23 Current 1 Prior 142 12 6 25 2 18 6' 17 2 15 1 104 1 0 7 1 1 2 15 3 8 0 38 *Data incomplete. ... 5.2% 23.0% 11.0% 4S .6% 33.3% 27.0% * W MW:/** Table 30 Chest x-ray and smoking Chest x-ray Normal j Total number 104 Abnormal j 38 Smokers No, % 53 - 51 25 66 Ex smokers ' No. % 23 22 Non-smokers No. % 28 27 6 16 7 IS Prevalence .of abnormal chest x-ray in persons with history of smoking not significantly different from that in non-smokers, 72= 1 083 n.s. w P' STTOOT fc-JWrfrWry.*- i "dtk Table 31 Chest x-ray Normal Chest x-ray and chronic bronchitis Total number 104 V His to ry of * chronic bronchitis No. % 20 21 No history of chronic bronchitis No. % 84 79 Abnormal 38 8 19 30 SI 100116 I U) S7 Table 32 Abnormal chest x-ray and abnormal peripheral circulation Chest X-Ray Normal L_ | Raynaud's j syndrome No. % 104 5 . 4.8 Abnormal 33 j 7 . 18.4 Cya nos is No. % 9 3.6 6 16.0 *^2= 6.657 p <0.01 Pseudo -clubbing No. % 8 7.7 7 18.4 Abnormal Allen test No. % 20 19 13 34 y~2= 3.501 n.s, ?' iT T O O T U> 9