Document zzNjBNk6q0jJaXnORLdBr4573

OLI 6817 n i JfiC- INDUSTRIAL HAZARDS OF PLASTICS AND SYNTHETIC ELASTOMERS Proceedings of the International Symposium on Occupational Hazards Related to Plastics and Synthetic Elastomers, Espoo, Finland, November 22-27,1982 Editors JORMA JARVISALO PIRKKO PFAFFLI HARRI VAINIO Institute of Occupational Health Helsinki, Finland ALAN R. USS, INC. NEW YORK 1M / Human# Hums 25. Omori, Y. (1976). Recent Progress in Safety Evaluation Studies on Plasticizers and Plstics and their Controlled use in Japan. Environ. Health Perspect. 17: 203-209. 26. Sontag, J.H., Page, N.P., and Saffiotti, U. (1976). Guidelines for Carcinogen Bioassay In Snail-Rodents. NCI Carcinogenesis Technical Report Series TR Ho. 1, National Cancer Institute, Bethesda, MO (USA). 6S pages. 27. Thefts, J.C., Stoner, G.D., Shimkin, M.B., and Heisburger, E.K. (1977). Tests for Carcinogenicity of Organic Contaminants of United States Drinking Haters by Pulmonary Tumor Response in Strain A Mice. Cancer Res. 37: 4ll Y 9Y<MI 28. USTIC (1981). Preliminary Report on U.S. Production of Selected Synthetic Organic Chemicals (including Synthetic .Plastics and Resins) March, April, and Cumulative Totals, 1983. United States Trade Commission, Hashington, O.C. Series C/P-83-4. 29. Wilbourn, J. and Montesano, R. (19B2). An Overview of Phtbalate Ester Carcinogenicity Testing Results: The Past. Environ. Health Perspect. 45: 127-128. i. t O f H t o\ 03 00 n* 8>nemlc ElMlonwra, (Q ISS-Ui it) taa aimii um. me., tan rath ** . me vm*. ny twm OCCUPATIONAL HAZARDS IN THE VC-KV'C INDUSTRY Hi 1lien J. Nicholson, Paul X. Heoneberger aod Herbert Seidmao. Rmvlroamental Seine*# Laboratory, Haunt Sinai School of Medicine of CINT, New York, Mew York 10029 (HJN, PH) and Amricia Cancer Society, 4 W. 35th Street, New ork, New York 10001 (HS). INTRODUCTION On January 24, 1974, The Wall Street Journal publish ed an article describing the occurrence of three deaths from itemsngiosarcoaa of the live-r among polyvinyl chloride (PVC) production workers at UM B.F. Goodrich Tire and Rubber Company plant in Louievil le, Kentucky. This announ cement shattered the relatively complacent view toward health effects associated wic.h plastic production in general and PVC production in .particular. At the time, U.S. and Western European production of vinyl chloride (VC) exceeded A x 10 metric toot*- Numerous mortality and clinical studies were undertaken in the major producing countries in an attempt to esi~*t>lish the extent of the carcinogenic risk and to identify clinical parameters useful for eurveillance of exposed groups. Because of the isuaediate concern in 1974, moet f these studies were com pleted between 1974 sod 1977. Several reviews and sympo sia on human health effects f.-iom VC exposure have been publiehed recently. A superb o*ue is by Lelbacb and Harateller (1981). The exposures were high that led to the disease observed in these various studiess* Typical concentrations in the industry were estiauted t-o be about 1,000 ppm prior to 1955, from 300-500 during 19955-1970, and from 100-200 during 1970-1974 (Baroea, 1976). However, variations from such exposures would have oc.curred in specific plants (Rowe, 1975). While historic**! average exposures were generally less than 1,000 ppm, peak exposures often ex- OLI 6819 cwdei 5-10,000 ppm (where worker* lost consciousneaa) and, on occasion, 40,000 ppm (where plants exploded). During 1974, exposures were reduced to about 10-70 ppm In the U.S. industry (Jones, 1981) and even further, follow ing the promulgation of a 1 ppa standard by -the Occupa tional Safety and Health Administration in 1974. MORTALITY STUDIES Of VC-EXPOSED WORKERS Table 1 ahows the populations observed and the follow up characteristics of twelve cohort studies of vinyl chlo ride exposed worker*. The studies were independent with the exception that the portions of the population reported in the Equitable Environmental Health Study (1978) were included in some other U.S. studies. The proportionate mortality study of Honson et al (1974) is not included as the VC-exposed individuals studied therein were Included in the cohort mortality study of Waxweller et si (1976). The site of the cohort* varied greatly, from 255 in the study of Nicholson et at (1975) to 9,677 in the Equitable Environmental Health study. A notable feature of all of the studies is that the populations followed were rela tively young or recently employed, even though many plants in the studies started product ion in the 1940s. Host workers were hired after 1950, when U.S. and Western European production increased sixfold in ten years (Nicholson and Henneberger, 1983). Thus, few deaths occurred among most of the groups observed and data on effect* 25 or more years from onset of exposure are li mited. The total mortality exceeded 10% of the observa tion cohort in only three studies. Further, the inclusion of recently employed individuals or those with short employswnt diluted the effects from VC exposure. Only five studies limited consideration to individuals with more than one year of exposure. In all cases, however, ose individuals with more than 20 years from onset of employment were available for observation. The follow-up terminated in the mid-1970s for all studies. Table 2 compare* the results for cancer of all sites and chronic liver disease in all 12 studies. Caocer is elevated in most of the studies, although it does not achieve a 0.05 level of significance except in the studies by Waxweiler et al (1976) and Nicholson et al (1975). In the study by Ott et al (1975), a highly exposed subgroup with 15 years latency had 8 caocer deaths coa^ared to 3.2 N f. I 1ST $a 1*4h* * | 2aSS8SsaS3SS ;j . 83 *5 M tr*i "* r- r* a 3,, U V ^ N 9 ts * mt I I !f g s 3 3 * S 3 i As 1 > -H -i fi??. S 3 is O IiI 6820 TabU 1 Ob.enred ami expected duiti .[ -<~Ti cXlorlda espeaad worker. la twal etodl.a Caocar of ell eltae Daatha StudT Obser. Kumc. aot Bmuil i ti VuffUr at al 1 ft. latency 10 t 0 jo. 5,It 4.14 97 154 Dt tyrea et el - -- Duck et al Eguttakle 14.44 *4 1 141.11 104* Pea a Celller US 134.77 tl heeude 8 1.9 114 lldwlm Ott at al IS yr. leteacy 9 u l.f 1**0 9.1 330 41 99 Jtalal at al 94 10.4 UI Therleult 4 Allerd 10 14.17 1U Uawailar at al JS U yr. leteecy 11 31.S 14.9 149t 144ft Chronic llvtr cancar PaatfcA Obaar. Exhc am 5 0_ 0 -- s. 14 34.4S J4tt 1 l.M U S 1.00 500* 1 (0.41 147 1 2.7 111 14 11.4 -- 3 4.0 03 - 50 adjusted for 1 cauaee ef death ( ) 1stleatad eai a sercaataea ef t.l. rate. t p < 0.05 tt f< 0.01 af control popularlorn .quell; kit* expected (p < 0.05). The absence of significant findings in other studies aay be attributed to tbeir low power. The study of lertazzi et si (1979) nay be biased because of low follow-up in the group. Fourteen percent of the population were uotraced and peraon-years at risk were calculated for these individuals as if they were alive. The low SHR of 44 for all causes of death suggests that proportionately wore deaths occurred in untraced groups than in the traced. The studies by Buffler et si (1979) Byreo et al (1976), Hasuda (1979), and Theriault and Allard (1981) had very few deaths available for analysis. That of Ott et al (1975) also war United by the nunber of deaths and further by virtue of a study group with rela tively lower exposure (through better industrial hygiene control). While having wore dealbs available for analysis (136), the study by Duck et al (1975) was significantly V&PVC Industry diluted by the inclusion of many individuals with very short and recent periods of exposure. Turning to chronic liver disease, one renarkable finding is the absence of significantly elevated aortality froa this cause in atost of the populations under observa tion. The only study with a significant elevation is that of Hasuda (1979) in which five deaths froa chronic liver disease occurred where only one was expected. However, this aust be considered in the light of an equally high aortality froa liver disease (6 observed vs. 1.4 expected) in a coaparison population followed for control purposes. Five of 62 deaths froa chronic liver disease seen in the study by Bertazzi et al (1979) are unusual, but the Imi tations of this study and lack of details aake evaluation difficult. The generally benign results in other studies contrast sharply with the severe liver disease froa VC exposure docuaented in clinical studies (Harsteller et al, 1975). Hepatoaegaly, hepatic fibrosis, portal hyper tension, and bleeding esophageal varices have coasnnly been found in individuals heavily exposed to VC, even without concoaitant exposure to alcohol. Table 3 lists the awirtality data for priaary cancer of the liver and biliary passages and for cancer of the lung, trachea and bronchus. In the case of liver cancer, the overall data are consistent and draaatic. Henangiosarcoaas of the liver were found in eight of the twelve studies. In each of the eight, a very large and highly significant SHR for liver cancer was seen. Methodological Imitations can account for negative data in the other four studies. The large SHR's observed, however,' are largely the result of low values for the expected nunber of cases rather than a high incidence of observed cases. Only 28 separate liver hesitngiosarcosis were identified in all twelve studies. As the overall excess nunber of deaths froa liver and biliary cancer in all studies was 47, soae heaangiosarcoaus aay not have been identified. The low nuabers aniat also be considered in light of the liaited follow-up tiaes in aost studies. The evidence for lung cancer is less clear. There is an elevation in soaw studies, but at a level that does not achieve statistical significance, except in the 15 year latency population of Waxweiler et al (1976). This, in part, aay be the result of the low power of axny of the OLI 6821 Tabic } OfcccrvcJ end expected death. tnm eelect.d ccuccc <cwi vinyl chior ide--ajtpo.cj wockctc Cancer of the Uw ml biliary Mluiu Oba." P. SiMR|la> SMI urcows Cancer of tie lung, treebee anil bronehue Oba. SMI fartetal ftultUi 5 yr. latency 0 (1.0)b (0.17) (000) tit _ yrea L0 yr. lataacy Duck 1* yr. latency 4 4 *, 0.97 0.60 -- 415t 509tt _ Equitable 10 15 yr. lataacy <*.5) (224)+ foa aad Col liar IS yr. latmcp 4 0.7* S63tt uu4* Ubolaoa Ott fatal flMlUwit 15 yr. lataacy 1 1 0 11 a o.t (0.11) (0.5) 0.1 (0.5) 1*7 (2S00)ttt -- 1523+++ (1600} ttt Kami Ur IS ft* Utncy 7 7 0.6 0.6 Uilttt 1606tt tatci of noedefllcetef heeeng1oeerconee 3 0 2 2 0 5 2 0 a 0 4 6 6 1 (7.7>c (91) s i.n U9* 4 1.49 260 3 1.70 160 16 14. 43 41 46 20 1 0 4(5T) 22 1 2 12 11 IS. S3 10.6* 44.29 31.0 51.23 26.0 (0.0) (1.1) 5.2 24.6 4.25 7*1 5.7 103 in 107 in 90 100 (125) _ 77(967) 95b )5 47 156 194t + < o.os +* < 0.01 +++ < 0.001 All verified liver ccetccr tleethe, Including thoc* e.i.bljehcd br review of oil cveUclle larornetioa. b ( ) Ipectef death. eeUeeted oo the bail* of 1950-1969 U.S. adjuatad rataa, ICO 115/ICO 1AO-205. c ( > - ft|ectei death. eetlaaced oa the baalc of actional eu ad lotted tetec. ICO 162-Jtl/ICP 140-205. 0 (tea fanaogUeuccaa occurr.d la a t*C fabricator, a Include. caacar of the feautaa. vw*c' I 101 studies. Only two hate an 101 power to detect an overall risk of 1.5 (Beauaonl and Breslow, 1981). Of signifi cance, however, are the very low SNR'a in the groups studied by Theriault and Allard (1981), Reinl, et al (1979), and Nicholson et al (1975), cohorts that would he expected to Manifest a high risk on the basis of the uany henangioaarccsBaa that were found. The four largest stu dies, although in sooe cases United by inclusion of short-tern and recently enployed workers, also sre note worthy for the SHR's rlose to 100. Uhere available, data on subcoborts with longer latency (> 15 yr) suggest sowe increased risk. Wsxweiler et al (1981) undertook a detailed analyaia of the exposure of those with lung cancer in their previ ously published study (Waxweiler et al, 1976) in an sttenpt to identify particular etiological agents. The analyaia used a serially additive expected dose Model (SMith et al, 1980) in which a dose measure during each year of exposure wax accumulated for each study individual for a variety of potentially carcinogenic agents. The cuMulative doses for those with lung cancer were coopered with those of other individuals in the plant under study. The results showed that the greatest correlation of luog cancer waa with exposure to PVC dust. Secondarily, expo sure to vinylidene chloride appeared to be inportaut, but only for large cell and adenocarcinoaw. The serially additive dose for VC uonoater differed little in those with lung cancer conpared to others in the plant, except, possibly, for large cell cancers. Thus, evidence to date does not establish that VC amnower it an iaportant lung carcinogen in exposed worker populations, although it ia recognized that United long term observation has ao far been available. In all stu dies considered here, a slight deficit of cases waa teen compared to the number expected. In the aubcohorta with ore than 15 yeart from onset of exposure, an overall excett of 10t waa observed. If, in addition, one consi ders a "healthy worker effect," any excess lung cancer would still be considerably less than the excess of liver cancer. A qualification to this conclusion ia that no study specifically considered cigarette usage. If cigar ette sinking was much less comsnn among VC workers than the general papulation, higher SHR's would have been seen if smoking specific dsta were available. However, this possibility is unlikely, considering the nany different populations studied. The uncertainty in huaan data is also reflected in animal studies. Increased lung cancers have been seen in nice but not in rats or banstera (Maltuni et al, 1981). Table 4 shows the results for brain and central nervous systeal cancers and for cancers of the lymphatic and henatopoletic systems. Cancers of the brain and central nervous aystea were significantly elevated in a nuaber of studies, although the results differed consider ably across studies. Again, negative data aay be simply the result of United long-tens follow-up or the low power of the study. In such cases the info mat ion is only sufficient to set an upper linit on relative risk of brain cancer. In contrast to lung cancer, however, the largest study group has a significantly elevated risk of brain and central nervous sysLeu aalignaocy. As with lung cancer, the data on brain and CHS cancer in animal. are equivocal. Neuroblastomas and brain Malignancies are observed in rats exposed to VC, but not among nice or boosters (Haltoni et al, 1981). The huaan data are also Mitigated by the recent finding of brain and central nervous systen tumors in a variety of cbeuical plant exposure circunstances (Alexander et al, 1980; Selikoff et al, 1982). Excess brain Malignancies, but not the etiological agents, have been identified in several Texas and Louisiana chemical/ petrochemical plants. VC exposure was documented for some cases, but it could not explain the overall findings. As individuals in sany of the VC studiea considered here were exposed to other chemicals and petrochemicals, the pos sible role of these agents cannot be excluded. Further, it has been suggested that aome working groups, with employer-paid medical plana, may have better case ascer tainment than in generally available (fireenwald et al, 1981) and, thus, more brain mslignancies identified. In any case, the nuaber of excess swlignancies of the brain and central nervous system (approximately 10) in all studies is considerably less than the nuaber of heaangiosarcomas identified in the sane populations. Similar results are obtained for malignancies of the lymphatic and hematopoietic system. here again, the analysis is United by the few deaths and disparate re sults which occurred in different studies. Overall, there would appear to be sn elevated risk, but the influence of OLI 6822 VC-FVCMuHryHuft'** I m Teh) a 4 Obitrrej and expected dcathe ftc Mltctal coiaeee font vinyl chlor 14a expoeed worhore Ceocer of the krai a 4 Center of the Ireohatic central tamua *Mtea end hematopoietic avatca krtaul Obeer, Expect., 3(01 1 (0.9)* 123 Obeer. Expect. SHE 4 (3.0)b (in) tutflat Efron 0 (0.1) - 2 0.11 612* 0 (0.5) 0- - Duck Equitable -- - 12 5.50 201* -20 IT.01 124 Tax 4 Collier 2 l.M 55 * 9.01 100 Kuud* 0 (0.15) - 0 (0.5) - Sicholeoe 1 (0.1) (1000) 2 (0.4) (500) Ott i 0.4 (150) i (1.6) (41) total 2 1.1 142 IS 7.7 214*1 Theriault 0 0.4 - 1 1.47 40 Homelier 5 1$ yr. leteocf $ 0.5 329 0.4 '450* 4 2.5 159 t < 0.0$ t+ < 0.01 * ( ) Expected eetlaated from the ratio of aga ataodardlaad 0.3. rata* 1CD 193/ICO 140-20$. b ( ) * bwciu ..tiaatad froo tha ratio of 1950-1969 U.S. ratos ICD 100-205/ICD 140-250. confounding exposures precludes definitive statenents. The overall excesa of such malignancies (about 10) is also SMCh less than those from primary hemangiosarcoaws of the liver. EFFECT OF REDUCTION OF EXPOSURE TO VC As mentioned previously, most mortality studies followed populations only to the 1972-1975 period. No data exist on the risk to previously exposed populations after cessa tion of exposure in 1974, although beaungiosarconas have been noted aawng retirees. We have recently completed a follow-up through 1981 of the population reported in 197S (Nicholson et al, 1975) to determine whether a high risk of liver cancer continues, following significant reduction in exposure. , The original group employed at a VC polymer- OLI 6823 lzation p* ..t in Niagara Falla, New York, baa been expanded by 40 additional workera, all eapoaed for live yearn, who achieved ten yearn fro* onaet of exposure subsequent to April 1974. Additionally, 195 individual, employed at a VC polymerization plant in Soutb Charleston. wet Virfiaia, vitfa five years of exposure and ten years from onset in December, 1964, were identified and traced Table 5 lists the observed and expected deaths by cause for both groups with the deaths occurring after 197* separately identified. (These are preliminary data; full Table I Ohssrvsd sod axpsctsd death* auea| Vtsrl chloride polysrlsetloa workers Blesere rolls. XT til * MSI (Jaoaary 1, lHt - Decsaber 11, 1(1) Cause of death Observed M-74 74-tl All CIMH 11 AL1 cuctr Lues 0 Coleu/reccaa 1 Irala 1 llvar 3 typhous 2 Vancraaa i Cirrhosis of User i Cardiovascular disease 13 u 2 2 0 i 0 1 Total 44 Id 2 3 1 1 1 2 H Enactad 40.ST 9.01 3.23 1*39 0.11 o. 0.11 0.50 1.41 1*.U SM 109 177* 42 m 303 115h 54 5* 200 142 lot South Charlaaton. Iff (X - 1> (Ncari>ar I* 1944 - Hac--tar 31, 1910) Causa el death Obaarvad is-)] 74-90 Total Bsaactad All causes It i* M 44.24 All caactr t 10 It 10.5 Lung 1 1 2 4.07 Celea/ractam 0 0 0 1.09 triia aa 0.41 Uw 0 4 4 0.23 typhous 0 0 0 o. Vaaeraaa a 0 0 0.47 Clrrboel* ef liver 0 1 i 1.91 Cardiovascular disease 12 20 17.14 sm 90 m 49 17_M_C H 71 a s < 0.05 bps 0.001 c pc 0.0003 V&SVCMue*-* Heard* / tag pathological review of all available specimens has not been completed.) Among t.he 44 deaths that occurred in the Niagara Falla cohort, 6 were from primary cancer of the liver, including 5 hemas giosarcoma a. Three of the beatangiosarcomas occurred in the period prior to 1974 and 2 subsequently. Similar findings occurred among the smaller group in West Virginia. Here, of 36 deaths, 4 were from hemangiosarcoms, all of which occurred subsequent to 1974. Thus, the risk of neoplcstic VC disease continues undiminisbed, even though exposures to the monomer have been significantly reduced. The coubined data from both groups are shown in Table 6 and demonstrate an excess risk of cancer, which is totally accounted for by the enormously increased risk of liver malignancy observed in each time from onset of exposure category. The excess lymphomas which achieved significance at the p < 0.0S level in the Niagara Falls group lose significance when combined with the data from South Charleston. A deficit of lung cancer was observed in both study groups and brain malignancies were about equal to the number expected. It is not certain whether the results of these two plants will be reflected in the results of other plants in future years. The South Charleston plant was the first facility to conawrcially produce VC. The New York plant opened immediately following the cessation of World War II. Thus, we are observing effects in populations that include many individuals with long times from onset of exposure. There is no information on whether the expo sures in these two plants were significantly different from those of the majority of other VC polyuerization facilities. It is known that pre-1974 exposures in the New York plant were sufficiently high to cause loss of consciousness to some individuals (4.51 of those examined in the clinical survey of 1974) (Lilis et al, 1975). MORBIDITY AND CLINICAL FINDINGS AMONG VC-EXPOSED WORKERS Clinical abnormalities from VC exposure predated by 25 years the documentation of its carcinogenicity. Vari ous VC-related abnormalities were reported in Eastern European literature. Including hepatomegaly (Tribukh et al, 1949), angioneurosis (Filatova and Gronsberg, 1957), osteolytic lesions of distal phalanges (Smirnova, 1961), Raynaud's phenomenon and sclerodermalike skin lesions (Suciu et al, 1963). However, VC disease was not seri- I OLI 6824 too* Ml* 6 flbi>rn4 --J aiweuJ Jmlii 11m .IdtI cHIotIJi tnowd wrtori 1b two polutriMtioa tl-- fro. onMt of womt Tun al*c wm of oxpoooro Caaaa of death 10 - U 10 - 30+ Tottl Okt. Ex*. All CMIHI All caaeir i* .n 7 1.71 Uag llnr rsla 1 l.H 1* O.Of 1 tyashpaa 1 0.27 CUikocli of llvor 0 0*7$ CtMlevMctlu AUoooo U g.74 0bo.--IfEc 30 14.01 9 7.30 1 1.36 V1 0.10 0 1 0.44 3 1.14 15 17.10 Obi* 16 31.04 11 6.01 2 3.00 > 0.17 0 0 0.41 0 0.07 11 10.40 0b*. &: 0 5.01 20 19.00 4 7.31 10 0.42 l 0.70 ) 1 .t& 3 f.il 41 41.71 *3 141 Ull 111 HI 103 M him years 3314 1714 1404 fe.a. iwmiMiitu 4 haaaaataaarcma tad 1 ktulu oualy considered in the West until the published descrip tion of Raynaud's syndrone, acroosteolysis, and pseudoscleroderma in two Belgium VC reactor cleaners (Cordier et al, 1966). Additional cases were soon noted (Vilton et al, 1967) and a comprehensive epidemiological study of 5,011 U.S. workers employed in production and polymeriza tion was undertaken. It showed that 11.9% had possible X-ray signs of acroosteolysis, conpared with 3.21 in a Hichi(an general population control group, with 21 defi nitely having Raynaud's phenomenon or X-ray evidence of acroosteolysis (Oilman et al, 1971). The conditions were clearly associated with the cleaning of reactors, in which a heavy exposure to VC occurred. Only one case of Ray naud's phenomenon occurred aaoag 557 workers employed in FVC fabrication. During the early 1970's, VC liver disease was de scribed in detail by Hsrsteller et al (1973, 1975). Observations on selected workers showed hepato- and splenooegsly to be comaun. Peritoneoscopy and guided liver biopsy identified severe portal hypertension in some, generally without cirrhotic fibrosis, although perisinuaoidal and focal or diffuse capsular fibrosis were common ly seen. Hie portal hypertension could lead to bleeding esophageal varices, with possible fatal consequences. In f 3S7 heavily eapoaed individuals, the portal hyperteusion and hepatic fibrosis often progressed after cessation of exposure (Hartin et al, 1976). The histology of awlignant and nonmalignant liver disease has been well described by Popper and Thomas (1975; l'hoauo et al, 1975), who suggest ed the possibility of an interrelationship between hemangiotarcoma and the proliferation of sinusoidal lining cells and bepatocytea seen in VC fibrosis. Lelbacb and Hsrsteller (1981) have alao noted that the vast majority of bemangioaarcoma cases have appeared on a background of some degree of hepatic fibrosis. The implications of these suggestions for s bemangioaarcoau dose-response relation are uncertain. During 1976, extensive studies were undertaken by tbe Environmental Sciencea Laboratory of the total workforces of three polymerization plants in tbe states of Hew York, Hichigan and West Virginia. Tbe results from the Hew York plant (Lilis et al, 1975) indicated the presence of acroo steolysis in hesvily exposed individuals. Hepato- and splenomegaly or hepatic tenderness was commonly observed and associated with duration of exposure and elevated alkaline phoiphataae levels. Sixty-four of 354 had an enlarged or tender liver or spleen sod of these, 41% had elevated alkaline phosphatase. Liver function tests were not particularly revealing, except for a correlation of elevated alkaline phosphatase levels with duration of exposure. Additionally, carcinogenic embryonic antigen titers were slightly higher among vinyl chloride exposed groups than in a smoking matched control populntion (Anderson et al, 1978). Tamburro and Greenberg (1981) have evaluated tbe effectiveness of federally mandated screening tests for vinyl chloride exposed workers. Figure 1 shows tbe re sults on specificity and sensitivity for 78 individuals with hepatic status determined by biopsy. ICG clesrance had the highest combined sensitivity and specificity, with SGPT tbe second most useful test. Elevated alkaline phosphatase had the greatest specificity of all tests, particularly for chemically-induced liver injury, but was lacking in sensitivity. SGOT and GCPT were of limited use because of their low specificity for chronic liver disease They recoasaended the use of ICG clesrance for screening, to be followed with alhaline phosphatase determinations for those with altered clearance. OLX 6825 i'. AP SOOT SGPT CCTP ICC TESTS 0.3 Figure I: Sensitivity and specificity of various biochemical screening tests and their sensitivity and specificity sum values (S i S) based on 70 vlth biopsy documentatloo of their hepatic statue. Three of the seven individuals who died after 1974 with bemangiossrcoma in the previously described mortality followup were examined in 1974. One, who died 22 Booths after examination, had no noteworthy abnormalities on exaainatioa (alkaline phosphatase was 90, slightly high). A second, who died three yesrs after esaaiinatioo, bad a slightly enlarged, palpable liver (11 s 6 cm) with normal blood counts and chemistry. Only one of the above drank alcohol at all and be only drank 2-3 beers/month. The third, who died 22 months after examination, had a slight ly enlarged liver (11 x 9 cm) and spleen (13 x 9 cm), and slightly elevated alkaline phosphatase (93), SGOT (52) and CEA (4.7). Thrombocytopenia was also present (73,000). No data are available on later clinical parameters, but the above results are clearly not sufficiently specific for identification of a special risk. Pulmonary abnormalities also have been associated with VC/PVC exposure. Sauli opacities, predominantly irregular, of profusion 1/0 or greater were found in 20 of 1,214 workers employed at PVC production in an Italian plaot (Hastrangelo et si, 1901). -All had been exposed to high levels of PVC dust (>10 s.g/m ). Lilia et si (1974) reported that approximately 20% of VC/PVC workers with high exposures to PVC dust bad abnormal X-rays, which correlated with duration of exposure sod, also, with cigsrette smoking. In contrast, only 4.7% of individuals in a PVC plant with low dust levels had abnoraul X-rsys. In addition to "typical pneumoconiosis," a granulatomous reaction to PVC dust has been reported (Arnsud et si, 1979). Hiller et si (1973) have observed pulmonary func tion abnormalities (s reduction in the ratios FEV./FVC snd ttiF/predicted WF) in both smokers snd non-smokers heavily exposed to PVC dust (and also to VC monomer). Haltoni and Lodi (1991), observed greater percentage of abnormal spu tum cytologies! results among VC exposed workers nxapsred to several other groups of manufacturing workers or miuera. Only workers in the chromium industry demonstrated a greater proportion of abnormal cells. Ducatman et el (1973) have observed an increased frequency of chromosome abnormalities in the lymphocyte cultures of VC worhera. Host of the abnormalities were "unstable" changes, such ss fragments, dicentrics, and rings. This was confirmed by Purchase et si (1978), ssng others. Some of the group studied by Purchase was resam pled 18 and 42 months later (Anderson et al, 1990). In those studied during January 1976, the frequency of abnor malities was increased in those who continued VC/PVC employment, but decreased in those who left the industry. In January 1978, no incrensed frequency wss found in any worker. The authors attributed the decrease to the reduc tion in VC exposure. HEALTH HAZARDS IN THE PVC PROCESSING INDUSTRY Prior to identification of benangiosarcoam in VC polyswrizatios workers, little effort was made to control either the concentration of residual monomer in PVC dust or exposures to dust snd VC that occurred in the various forming operations of the PVC fabricating industry. VC concentrations in excess of 10 ppn occurred frequently. Mtile these concentrations were significantly lower than those of the polymerization industry, the much greater employment in the processing industry (hundreds of thou sands 'vs. tens of thousands in the polymerization work) raised concern for population health effects, particularly for malignant disease for which no threshold was known. However, only two hesrsngiosarcoars s have been docuatented in O LI 6826 tbe PVC processing industry, one in an accountant io a plut wkiB| PVC fabric and one in an Italian plant asking PVC sacks. A third esse nay have occurred in an electri cal Hire insulator, but tbe pathological diagnosis ia uncertain (Lloyd, 1915). This is in contrast 1^.11 cases known to have occurred anong polynerization workers (HIOSH, 1982). This is aonewhat contorting and indicates a signi ficantly lower total VC-related neoplastic risk anong fabrication workers. However, it should be noted that case finding ia likely to be poorer in this group than in polynerisation workers. A proportionate atortality study has been conducted of (,341 deaths of fomer employees of IT PVC fabricators (Cbissse Jr., et al, 19TT). The direct PWt's suggested an eaceaa in total cancer nortality satong both white nea and white wonen with tbe najor escessea concentrated in can cers of the digestive organs. An excess of breast cancer was also seen ia wonen, but not confined in a case-con trol study (which was of very low power and could only detect a threefold increased risk) (Cbiazze, Jr. et al, 1980). The results of the proportionate nortality study aunt bo considered cautiously. In such studies, elevated cancer riaka and are typically seen because of a "healthy worker effect," which leads to a reduction in cardiovascu lar deatba relative to those of cancer. If PCHR's (pro portionate cancer nortality ratios) had been calculated, rather than PMI's, digestive cancer would atill be elevat ed but not at an 0.05 level of significance. Interest ingly, an excess of stonach cancer was seen io tbe propor tional nortality study of Baxter and Pox (19Tb). SIMHAKT ^Overall, the results of the analysis of 12 studies of VC production and polynerisation workers denonstrate an eno'rnously elevated risk of liver nslignancies, the possi bility of a twofold increased risk of brain and central nervous syaten tunors and perhaps, also, of nslignancies of tbe lynphatic and henatopoietic syaten. However, the role of other agents cannot be excluded in the etiology of nonhepatic nslignancies. Bronchogenic carcinoma does not appear to be increased fron exposures to VC aonoaer, although a relationship to PVC dust was suggested in one study. These conclusions nus'. be considered in light of United data on worhera followed more than 25 years fron VC*WC jwrtnscry Haiwda / in onset of exposure. Considering the nunbera of observed and expected deaths in all studies, it would appear that the excess of nslignancies at nonhepatic sites ia lesa than tbe excess of liver tunors. Data presented elsewhere in this volune (Nicholson and Henneberger, 1981) suggest that exposure reductions in 1174 nay have virtually elininated tbe VC-sssocisted risk of liver cancer if tbe current U.S. standard is net. To the extent that VC exposure is associated with other cancers, a ainilar risk reduction would be expected. Raynaud's phenonenou, acroosteolysis, sclerodermalike skin lesions, hepsto- and splenomegaly with noncirrhotic hepatic fibroaia, and severe portal hypertension have been associated with past heavy exposures to VC. Evidence exists that tbe liver diaease and portal hypertension nay progress following cessation of exposure. However, all of tbe above syndromes were found largely in heavily exposed individuals. Their occurrence would be much leas likely in workers exposed only to concentrations currently allow ed. . Pulaonary deficits, X-ray abnormalities, and, per haps, lung cancer have been associated with VC/PVC expo sure. Because of tbe possible contribution of PVC dual to these findings, engineering controls during polymer dry ing, bagging and nssge are warranted .j REFERENCES Anderson HA, Snyder HS, Levinson T, Woo C, Lilia R, Selifcoff IJ (1978). Levels of CEA among vinyl chloride and polyvinyl chloride exposed workers. Cancer 42:1560-1567. 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