Document bZBmpvmwZy7DNn43b4pjYoJg

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 P1RKKO PFAFFLI HARRI VAINIO Institute of Occupational Health Helsinki, Finland ALAN R. LISS, INC. NEW YORK OLI 3825 1M / Huff and Khnw 25. Omori, 1. (1976). Recent Progress lit Safety Evaluation Studies on Plasticizers and Plsties and their Controlled use tn Japan. Environ. Health Perspect. 17; 203-203. 26. Sontag, J.M., Page, N.P., and Safftotti, U. (1976). Guidelines for Carcinogen Bioassay In Small-Rodents. NCI Carcinogenesis Technical Report Series TR No. 1, National Cancer Institute, Bethesda, HD (USA). 65 pages. 27. Theiss, J.C., Stoner, G.O., Shlmkin, H.B., and Welsburger, E.K. (1977). Tests for Carcinogenicity of Organic Contaminants of United States Drinking Waters by Pulmonary Tumor Response in Strain A Mice. Cancer Res. 37: 2717-2720. 28. USTIC (1983). 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, Washington, D.C. Series C/P-83-4. 29. Uilbourn, J. and Hontesano, R. (1982). An Overview of Phthalate Ester Carcinogenicity Testing Results: The Past. Environ. Health Perspect. 45: 127-128. Jb. I OLI 3826 I J IwduaMH HMfO<U Ptaaifc, and SynOwtic Ft--tanurm, pg-- ttt-tra C tSM Man It Um, Inc., IS* WTOi A--.. Haw Vwk, NY IBOtt OCCUPATIONAL HA2ARDS IK THE VC-J^C INDUSTRY William J. Kicbolaon, Paul I. Henneberger and Herbert Seldmea. fnviror--etl ScicocM Laboratory, Mount Sinai School of Mediclme mt CUNT, Hew York, Hew York 10029 (KJH, PH) and American Cancer Society, 4 W. 35th Street, Hew York, Hew fork 10001 (HS). INTRODUCTION On January 24, 1974, The Wall Street Journal published an article describing the occurrence of three death* from bemanglosarcoma of the live-r among polyvinyl chloride (PVC) production workers nt Ut*c B.F. Goodrich Tire and Rubber Company plant in Louisvll le, Kentucky. This announ cement shattered the relatively complacent view toward health effects associated vitd> plastic production in general and PVC production in -particular. At the time, U.S. and Western Buropean production of vinyl chloride (VC) exceeded 6 x 10 metric toots. Numerous mortality and clinical atudies were undertaken in the major producing countries in an attempt to establish the extent of the carcinogenic risk and to identify clinical parameters useful for surveillance of exposed groups. Because of the iMsedlate concern in 1974, most f these studies were com pleted between 1974 and 1977. Several reviews and sympo sia on human health effects frrom VC exposure have been published recently. A superb one is by Lelbach and Marsteller (1981). The exposures were high -that led to the disease observed in these various studies* Typical concentrations in the industry were estimated tto be about 1,000 ppm prior to 1955, from 300-500 during 19955-1970, and from 100-200 during 1970-1974 (Barnes, 1976). However, variations from such exposures would have occcurred in specific plants (Rowe, 1975). While historical average exposures were generally less than 1,000 ppm, pesk exposures often ex- 1M t Nicholson, Msnnabsrosr, and Mdman ceeded 5-10,000 ppa (where workers lost consciousness) and, on occasion, 40,000 ppa (where plants exploded). During 1974, exposures were reduced to about 10-20 ppa in the U.S. industry (Jones, 1981) and even further, follow ing the proaulgation of a 1 ppa standard by-the Occupa tional Safety and Health Adminiatration in 1974. MORTALITY STUDIES OF VC-EXPOSED WORKERS Table 1 shows the populations observed and the follow up characteristics of twelve cohort studies of vinyl chlo ride exposed workers. The studies were independent with the exception that the portions of the population reported in the Equitable Environnental Health Study (1978) were included in soae other U.S. studies. The proportionate mortality study of Konson et al (1974) la not included aa the VC-exposed individuals studied therein were included in the cohort nortslity study of Waxweller et al (1976). The aixe of the cohorts varied greatly, from 255 in the study of Nicholson et al (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 aany plants in the studies started production in the 1940a. 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 aost of the groups observed and data on effects 25 or aore years from onset of exposure are li mited. The total aortality exceeded 1QK of the observa tion cohort in only three studies. Further, the inclusion of recently employed individuals or those with short employment diluted the effects fron VC exposure. Only five studies limited consideration to Individuals with aore than one year of exposure. In all cases, however, sosk individuals with aore than 20 years froa onset of employment were available for observation. The follow-up terminated in the aid-1970s for all studies. Table 2 compares the results for cancer of all sites and chronic liver disease in all 12 studies. Cancer is elevated in moat of the studies, although it does not achieve a 0.05 level of significance except in the studies by Waxweller 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 S cancer deaths compared to 3.2 VomvC Industry Horan* I 1*7 n*i lh iss 8d *A3 hga ill HI Si wi ms01 s0% 2 x si x i st 5 x. 3fHi9t'il *3 i5j1: 3 ft S S *8 8 -1* gaSs s8 S I ] *, 1 a K *4 5 n 3 i M 3 3 J 5 3 p- th I H H H H H I i I is >a j s 3*2 s* * *. s t i : sss OLI 3827 IS# t Mchotooft, Honnebergcr, end Mdnun Table 2 Obaerved and expected deptha caoot vlttrl chloride onpoaod worker* 1b tvelv* etudlo* Cancer of all oleoa Death* Stud* Obtor. Expee. SHt Eertaiil *e *1 30 30.9 97 Buffler et *1 5 jrr. Uctscjr a 4 5.19 154 4.34 13# ftjrrcn *E *1 - -* Duck it *1 35 34.44 94 Equitable 139 141.39 104* fox | Collier 115 126.77 91 Haaud* 5. a ua Nicholson 9 3.9 130 Ott ,t al 13 15 yr, Uttecy 9 16.0 9.2 *i 94 total *t *1 94 90.6 111* Theriault 4 Allard 10 14.31 111 Viwtllir it *1 35 IS yrr. latency 31 33.5 14.9 149t iam Chronic liver cancer DeeeH SHt S 0 0_ __ 14 16.45 54tt 1 1.41 31 5 1.00 MO* 1 (0.) 161 3 1.7 111 U ia.4 -_ 1 4.0 41 . 30 * Ujuatcd for ubkon Mum of death t ) Estimated u o percentage of O.S. cat** t p < 0.05 tt >< 0.01 a SUM of control population equally high expected (p < 0.05). The absence of significant findings in other ltudies say be attributed to their low power. The study of Bertazzi et al (1979) may be biased because of low follow-up in the group. Fourteen percent of the population were uotraced and person-years st risk were calculated for these individuals as if they were alive. The low SHR of 44 for all causes of death suggests that proportionately More deaths occurred in untraced groups than in the traced. The studies by Buffler et al (1979), Byren et al (1976), Hasuds (1979), and Theriault and Allard (1961) had very few deaths available for analysis. That of Ott et al (1975) also was United by the nuaber of deaths and further by virtue of a study group with rela tively lower exposure (through better industrial hygiene control). Uhile having store deaths available for analysis (136), the study by Duck et al (1975) was significantly VC^VC Mushy Hsasds I 1SS diluted by the inclusion of many individuals with very short and recent periods of exposure. Turning to chronic liver disease, one reaurkable finding is the absence of significantly elevated Mortality froa this cause in Most of the populations under observa tion. The only study with a significant elevation it 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 Mortality froa liver disease (6 observed vs. 1.4 expected) in s comparison population followed for control purposes. Five of 6Z deaths froa chronic liver disease seen in the study by Bertazzi et al (1979) are unusual, but the Uni tstions of this study and lack of details sake evaluation difficult. The generally benign reaulte in other studlea contraat sharply with the severe liver disease froa VC exposure documented In clinical studies (Harsteller et si, 1975). Hepatoaegaly, hepatic fibrosis, portal hyper tension, sad bleeding esophageal varices have commonly been found in individuals heavily exposed to VC, even without concoaitant exposure to alcohol. Table 3 lists the aortality data for primary cancer of the liver and biliary paasagea and for cancer of the lung, trachea and bronchos. In the case of liver cancer, the overall data are consistent and dramatic. Heaaogioaarcoaaa of the liver were found in eight of the twelve studies. In each of the eight, a very lerge and highly significant SHR for liver cancer wee seen. Methodological linltations can account for negative data in the other four studies. The large SMS'a observed, however,' are largely the result of low values for the expected number of cases rather than a high incidence of observed cases. Only 28 separate liver hemangioaarcomaa were identified in all twelve studies. As the overall excess number of deaths from liver and biliary cancer in all studies was 47, some hemaugiosarcomaa may not have been identified. The low numbers must also be considered in light of the limited follow-up times In most studies. The evidence for lung cancer is less clear. There is an elevation in tome studies, but st a level that does not achieve statistical significance, except in the 15 year latency population of Haxweiler et al (1976). This, in part, nay be the result of the low power of many of the OLX 3828 Table 3 Observed and expected death* from eelected ciumi aaong vinyl chloride-exposed worhtre Cancer of the liver and biliary oaiaagea Oba. E- BemangioSHR aarcomae Cancer of the lung, trachea and bronchus lertuti Buf fler 5 yr. latency B 0 U.D>h (0.17) (SOO)ttt _ Syren 10 yr. latency Buck 19 yr. latency 4 4 _ 0.97 0.68 __ 413+ 589++ Equitable 10 15 yr. latency (4.5) (22*)+ Tox and Collier 15 yr. latency 4 0.71* 563++ Kaauda Nicholson Ott Be ini Theriault 13 yr. lataacy 1 3 0 12 8 0.6 (0.12) (0.5) 0.9 (0.5) 167 (2500)+++ -- 1523+++ (1600) t+t Vaxvellar 15 yr. latency 7 7 0.6 0.4 1155+++ 1606++t Total of oondupllcatad hemengloaarccwae 3 0 2 2 5 2 0 3 0 4 8 6 6 7 o.i>c 1.73 289+ 4 1.49 266 i.7a 166 14 43 41 28 1 0 4(5?) 22 2 2 L2 11 IS.33 10.69 44.29 37.0 31.23 26.0 (0.6) (1.1) 5.2 24.6 5.76 4. 25 7.7 5.7 103 131 107 111 90 106 (125) 77(967) 95* 35 47 156 194+ 29 + < 0.03 +t < 0,01 + + + < 0.001 a 411 verified liver cancer deatha. Including revlev of all available Information. thoee eatabllahed hy b ( > * Expected deatha eetinated on the baeie of 1950-1969 0.S adjuatad ratea, ICO 155/ICD 140-205. c ( ) - Expected deatha eetlmated on tba baala of national eta adlueted ratea, ICO 162-163/ICO 140-205. *J <1 One haaongloearcona occurred in a MC fabricator. Include. cinctr of th pence.. VC-PVC m<u<lf> Wiwrtl I -Ml studies. Only two h\e an SOI power to detect an overall rlik of 1.5 (Beauaom. and Brealow, 1961). . Of significance, however, are the very low Sfffi'a in the groups studied by Theriault and Allard (1981), Reini, et al (1979), and Nicholson et al (1975), cohorts that would be expected to want felt a high risk on the basis of the a.ny heaangioaarcoaas that were found. The four largest tudiet, although in aowe caaea Halted by inclusion of short-tern and recently eaployed worker!, also are note worthy for the SHR'a close to 100. Where available, data on aubcohorts with longer latency (> 15 yr) suggest some increased rlak. Waxweiler et al (1981) undertook a detailed analysis of the exposure of those with lung cancer in their previ ously published study (Waxweiler et al, 1976) in an at tempt to identify particular etiological agents. The analysis used s serially additive expected dote aodel (Saith et al, 1980) in which a dose aeaaure during each year of exposure was accuaulated for each study individual for a variety of potentially carcinogenic agents. The emulative doses for those with lung cancer were coapared with thoae of other individuals In the plant under study. The results showed that the greatest correlation of lung cancer was with exposure to PVC dust. Secondarily, expo sure to vinylldene chloride appeared to be iaportsnt, but only for large cell and adenocarcloans. The serially additive dose for VC monomer differed little in those with lung cancer coapared to others In the plant, except, possibly, for large cell cancers. Thus, evidence to date does not establish that VC snnoaer la an laportant lung carcinogen in exposed worker populations, although it la recognized that Halted longtera observation has so far been available. In all stu dies considered here, a slight deficit of cases was seen coapared to the umber expected. In the aubcohorts with aore than 15 years froa onset of exposure, an overall excess of 101 was 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 looking was oiuch leas coaaon aaong VC workers than the general population, higher fOflt's would have been seen if saoking specific data were available. However, this OLI 3829 possibility it unlikely, considering the lany different populations studied* The uncertainty in human data it also reflected in animal studies* Increased lung cancers have been seen in nice but not in rats or hanstect (Haltoai et al, 1981). Table 4 shows the results for brain and central nervous system cancers and for cancers of the lynphatic and hematopoietic systeaa. Cancers of the brain and central nervous systea were aignificantly elevated in a number of studies, although the results differed consider* ably across studies* Again, negative data aay be simply tbe result of Halted long-term follow-up or the low power of the study. In such cases the Information ia only sufficient to set an upper Halt 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 nervoua system malignancy. As with lung cancer, the data on brain and CHS cancer in aniaals are equivocal. Neuroblastomas and brain malignancies are observed in rats exposed to VC, but not among aice or hamsters (ttaltoni et al, 1981). The human data are also mitigated by the recent finding of brain and central nervoua system tumors in a variety of chemical plant exposure circumstances (Alexander et al, 1960; Selikoff et al, 1962). Excess brain malignancies, but not the etiologicsl 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 many of the VC studies considered here were exposed to other chemicals and petrochemicals, the pos sible role of these agents cannot be excluded. Further, it baa been suggested that some working groups, with employer-paid medical plans, may have better case ascer tainment than is generally available (Greenwald et al, 1961) and, thus, more brain malignancies identified. In any case, the number of excess malignancies of the brain and central nervoua system (approximately 10) in all studies is considerably less than the number of bemangiosarcomas identified in the same populations. Similar results are obtained for malignancies of the lymphatic and hematopoietic system. Here again, the analysis is limited by the few deaths and disparate re sults which occurred in different studies. Overall, there would appear to be an elevated risk, but the influence of Table 4 Obawred and wwctri diatha from naloctod canoaa --oaa vtinrl chloride exacted nwUti Cancer of the brala I Ceacer et the lmlntle central nerveea are tern end bonatopolotlc eraten Mrtaasl (bur. bCMCt. 1 (0.t>* 125 Obaor. Enact. SHK 4 O.0)b an) Bufflor 0 (0.1) - 0 (0.1) - Byron 2 o, 0- - Ouch IqvlttbU -- - 11 5.90 101* -- - 20 17.01 124 ! 4 Colllor 2 3.66 S3 9 9.01 100 Kaavda D (O.U) - 0 (O.J) - Xteholaoo 1 (0.1) (1000) 2 .*) (100) Ott ialal Tborlaalt 1 0.4 (1) 2 i.i 161 0 0.6 - 1 (l.() (1) 13 7.7 ll*9t 1 1.67 60 Uaxwallor i 15 yr. latency 3 0.9 119 0.6 498* 4 2.5 139 t a 0.05 tt a 0.01 * ( ) Expected eetlaated from the retie of age standardised t.8. ratea ICO 195/10 140-203. b ( ) - Expected eatlaatod from the retie of 1930-1969 0.8* retee 1CD 200-203/10 1*0-250, confounding exposures precludes definitive statements. The overall excess of such malignancies (about 10) is also much less than those from primary hemangioaarcomas 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 hemangiosarcomas have been noted among retirees. We have recently completed a follow-up through 1981 of the population reported in 1975 (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 3830 1M / Mteholion, Memeberger, and teMman ixatlon plant in Niagara Tails, Haw York, has been ex panded by 40 additional workers, all exposed for live years, who achieved ten years from onset of exposure subsequent to April 1974. Additionally, 195 individuals employed at a VC polymerization plant in South Charleston, West Virginia, with five years of exposure and ten years fron onset in December, 1966, were Identified and traced through 1980. Table S lists the observed and expected deaths by cause for both groups with the deaths occurring after 1974 separately identified. (These are preliminary data; full Table 5 Obaerved aad expeeted deethe aaong lnyl ehlorlda polymerisation vorkara Wlmti Falla, iff . <IT (January 1* 1956 - Deeeabar 31, 1981) Cauaa of death Obaerrad 56-74 74-81 811 cauaea 23 811 cancer B Lung 0 Colon/reetua 1 Brain 1 liver 3 Irnphona 1 faocraae 1 Clrrboeia of liver 1 Cardiovaaeular dlaeaae 13 21 B 2 2 0 3 1 0 1 8 Total 44 16 2 3 1 6 3 l 2 21 Enact ad 40.87 9.01 3.23 1.39 0.33 0.19 0.S5 O.SO 1.41 19.88 SHR 108 177* 62 216 303 JiSSb 545* 200 142 106 South Charleston. WV . t* - 195) (Deccaber 1, :1966 - December 31. I960) Cauea of death Observed 66-73 74-80 811 cauaea 811 cancer 11 2 Lus| Colon/rectua Brain I 0 0 tlvar 0 Lynphona 0 fancreaa Clrrboeia of liver 0 0 Cardiovaaeular dleaee* 8 24 10 1 0 0 4 0 0 1 12 Total 36 12 2 0 "0 4 0 0 1 20 Exoactad 44.74 10.65 4.07 1.89 0.43 0.23 0.59 0.67 1.81 27.24 srat 80 113 49 1739* __ 55 73 a p< 0.05 b p < 0.001 c p < 0.0005 VC-RVC Industry Heard* / IK pathological review of all available specimens has not been completed,) Among the 44 deaths that occurred in the Niagara Falla cohort, 6 were from primary cancer of the liver, including 5 beaunglosarcomas. Three of the hemanglosarcomas 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 hemangiosarcoma, all of which occurred aubaequent to 1974. Thus, the risk of neoplastic VC disease continues undimi nished, even though exposures to the monomer have been significantly reduced. The combined 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 tine from onset of exposure category. The excesa lymphomas which achieved significance at the p < 0.05 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 resnlta 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 commercially produce VC. The New York plant opened insKdiately following the cessation of World War II. Thus, we are observing effects in populations that include smny 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 polymerization facilities. It is known that pre-1974 exposures in the New York plant were sufficiently high to cause loss of consciousness to some individuals (4.5X of those examined in the clinical survey of 1974} (Lilia 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), angioneurosio (Filatova and Gronsberg, 1957), osteolytic lesions of distal phalanges (Smirnova, 1961), Raynaud's phenomenon and aclerodermalike akin lesions (Suclu et si, 1963). However, VC dlaesse was not seri- OLI 3831 Tibia 4 Obaarrad aaJ aabactad daatba aaont ylnTl chlorld. .spo.ed workers In two palraarlaatioa faalllciaa ba tlaa from anaat at aapoaura Cauaa of A.sth Taara alaca oaaat of 10 19 79-29 30* Total All cauaaa All cancar Liaar Iralo CarAloaaacular Ob*. RjCO, 24 19.13 7 3.72 1 1.26 2* 0.08 2 0.2? tr 0 0.26 14 1.74 0b*. 30 34.03 9 7.98 1 2.9b 3* 0,18 0 1 0,46 3 1.24 13 17. S8 Ob*. 26 31.84 12 8.03 2 3.08 5* 0.17 0 0 0.41 0 0.87 12 18.40 Ob*. 80 85.81 28 19.86 4 7.31 10 0.41 1 0.78 3 1.14 3 2.85 41 41.73 SHft 93 142 35 23(1 132 283 105 96 Paraoa paara 1924 1114 a. baaangloaarcoaa b. 4 haaaogioaarcoaaa and 1 hapatoaa ously considered in the Vest until the published descrip tion of Raynaud's syndrome, acroosteolysls, and pseudoscleroderma in two Belgium VC reactor cleaners (Cordier et al, 1966). Additional cases were soon noted (Wilson et al, 1967) and a comprehensive epidemiological study of 5,011 11.S. workers employed in production and polymeriza tion was undertaken. It showed that 11.9)1 had possible X-ray signs of acroosteolysis, compared with 3.ZJ in a Michigan general population control group, with 2$ defi nitely having Raynaud's phenomenon or X-ray evidence of acroosteolysis (Dinman 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 among 557 workers employed in PVC fabrication. During the early 1970's, VC liver disease was de scribed in detail by Harsteller et al (1973, 1975). Observations on selected workers showed hepato- and sple nomegaly to be common. Peritoneoscopy and guided liver biopsy identified severe portal hypertension in some, generally without cirrhotic fibrosis, although perisinusoidal and focal or diffuse capsular fibrosis were common ly seen. The portal hypertension could lead to bleeding esophageal varices, with possible fatal consequences. In V&PVC Musty Hoards /1(2 heavily exposed individuals, the portal hypertension and hepatic fibrosis often progressed after cessation of exposure (Martin et al, 1974). The histology of malignant and nonmallgnant liver disease has been well described by Popper and Thomas (1975; Thomas et al, 1975), who suggest ed the possibility of an interrelationship between heaangiosarcoma and the proliferation of ainuaoidal lining cells and hepatocytea seen in VC fibrosis. Lelbach sod Harsteller (1981) have also noted that the vast majority of hemangloaarcoma cates have appeared on a background of some degree of hepatic fibrosis. The implications of these suggestions for a hemanglosarcoma dose-reaponae relation are uncertain. During 1974, extensive studies were undertaken by the Environmental Sciences Laboratory of the total workforces of three polymerization plants in the states of Hew York, Michigan and Vest Virginia. The results from the Hew York plant (Lills et al, 1975) indicated the presence of acroosteolyais in heavily. exposed individuals. Hepato- and splenomegaly or hepatic tenderness was conmonly observed and associated with duration of exposure and elevated alkaline phosphatase levels. Sixty-four of 354 had an enlarged or tender liver or spleen and of these, 41% had elevated alkaline phosphatase. Liver function testa were not particularly revealing, except for a correlation of elevated alkaline phoaphataae levels with duration of exposure. Additionally, carcinogenic embryonic antigen titers were slightly higher among vinyl chloride exposed groups than in a smoking matched control population (Anderson et al, 1978). Tahburro and Greenberg (1981) have evaluated the effectiveness of federally mandated screening testa for vinyl chloride exposed workers. Figure 1 show* the re sults on specificity and sensitivity for 78 individuals with hepatic status determined by biopsy. ICG clearance had the highest combined sensitivity and specificity, with SGPT the second moat useful test. Elevated alkaline phoaphataae had the greatest specificity of all teata, particularly for chemically-induced liver injury, but was lacking in sensitivity. SCOT and GGPT were of United use because of their low specificity for chronic liver disease They recommended the use of ICG clearance for screening, to be followed with alkaline phoaphataae determinations for those with altered clearance. OLI 3832 1SS t Mchotaon. and tiWiwn TESTS Figure 1: Sensitivity and specificity of various biochemical screening tests and their sensitivity and specificity sum values (S 1 S) based on 76 with biopsy documentation of their hepatic status. Three of the seven individuals who died after 1974 with hemsngiotarcoma In the previously described mortality followup were examined in 1974. One, who died 2! months after examination, had no noteworthy abnormalities on examination (alkaline phosphatase was SB, slightly high). A second, who died three years after examination, had a slightly enlarged, palpable liver (11 x 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 S cm) and spleen (13 x S cm), and slightly elevated alkaline phosphatase (93), SOOT (52) and CEA (4.7). Thrombocytopenia was also present (75,000). Mo data are available on later clinical parameters, hut the above results are clearly not sufficiently specific for identification of a special risk. Fulmonary abnormalities also have been associated with VC/PVC exposure. Small opacities, predominantly irregular, of profusion 1/0 or greater were found in 20 of 1,216 workers employed at PVC production in an Italian plant (Hastrangelo et al, 1961). .All had been exposed to high levels of PVC dust (>10 iig/mJ). Lilia et al (1976) V&PVCMimny Hassids / ISO reported that approximately 20% of VC/PVC workers with high exposures to PVC dust had abnormal X-rays, which correlated with duration of exposure and, also, with cigarette smoking. In contrast, only 4.7% of individuals in a PVC plant with low dust levels had abnormal X-rays. In addition to "typical pneumoconiosis," a granulatomous reaction to PVC duat has been reported (Arnaud et al, 1978). Hiller et el (1975) have observed pulmonary func tion abnormalities (a reduction in the ratios FEV./TVC and MHF/predicted HHF) in both smokers and non-smokers heavily exposed to PVC duat (and also to VC monomer). Haltonl and Lodi (1981), observed greater percentage of abnormal aputum cytological results among VC exposed workers compared to several other groups of manufacturing workers or miners. Only workers in the chromium industry demonstrated a greater proportion of abnormal cells. Oucatman et al (1975) have observed an increased frequency of chromosome abnormalities in the lymphocyte culturea of VC worker*. Host of the aboormalitiet were "unstable" changes, such as fragments, dicentrics, and rings. This was confirmed by Purchase et al (1978), among others. Some of the group studied by Purchase was resampled 18 and 42 mouths later (Anderson et al, 1980). In those studied during January 1976, the frequency of abnornsllties was increased in those who continued VC/PVC employment, but decreased in those who left the industry. In January 1978, no increased frequency was found in any worker. The authors attributed the decrease to the reduc tion in VC exposure. HEALTH HAZARDS 1H THE PVC PROCESSING INDUSTRY Prior to Identification of henangioaarcoms in VC polymerization workers, little effort waa made to control either the concentration of residual monomer in PVC dust or exposures to dust and VC that occurred In the various forming operations of the PVC fabricsting industry. VC concentrations in excess of 10 ppm occurred frequently. While these concentrations were significantly lower than those of the polymerisation Industry, the much greater employment in the processing industry (hundreds of thou sands vs. tees of thousands In the polymerisation work) raised concern for population health effects, particularly for malignant disease for which no threshold waa known. However, only two beaungiosarcoaui have been documented in OLI 3833 VCPVCtidueey Hoards / 1T1 ..sing industry, one in so accountant in a onset of exposure. Considering the numbers of observed ^.Oiit naking PVC fabric and one in an Italian plant asking and expected deaths In all studies, it would appear that PVC sacks. A third caae nay have occurred in an electri the excess of malignancies at nonhepatic sites ia leas cal vire insulator, but the pathological diagnosis is than the excess of liver tumors. Oats presented elsewhere uncertain (Lloyd, 1975). This is in contrast tq,.85 cases in this volume (Hicholaon and Henneberger, 1983) auggeat known to have occurred sarong polymerization workers (NIOSH, that exposure reductions in 1974 may have virtually elimi 1982). This is somewhat comforting and indicates a signi nated the VC-aasociated risk of liver cancer if the ficantly lower total VC-relsted neoplastic risk sarong current 1).S. standard ia met. To the extent that VC , fabrication workers. However, it should be noted that exposure ia associated with other cancers, e similar risk case finding is likely to be poorer in this group than in reduction would be expected. polymerization workers. Raynaud's phenomenon, acrooateolyaia, sclerodermalike A proportionate aortality study has been conducted of 4,341 deaths of foraer employees of 17 PVC fabricators (Chiazze Jr., et al, 1977). The direct FMR's suggested an excess in total cancer arortality among both white iron and white women with the major excesses concentrated in can cers of the digestive organs. An excess of breast cancer was also seen in women, but not confirmed in a case-con trol study (which was of very low power and could only detect a threefold increased risk) (Chiazze, Jr. et ai, 1980), The results of the proportionate arortality study must be considered cautiously. In such studies, elevated cancer rir' and are typically seen because of a "healthy worker e which leads to a reduction in cardiovascu akin leaions, hepato- and splenomegaly with nonclcrbotlc hepatic fibrosis, and severe portsl hypertension hsve been associated with past heavy exposures to VC. Evidence exists that the liver disease and portal hypertension may progress following cessation of exposure. However, all of the above syndromes were found largely in heavily exposed individuals. . Tbeir occurrence would be much less likely in workers exposed only to concentrations currently allow ed. . Pulmonary deficits, X-rey abnormalities, and, per haps, lung cancer have been associated with VC/PVC expo sure, Because of the possible contribution of PVC dust to these findings, engineering controls during polymer dry ing, bagging and usage are warranted lar dr ve to those of cancer. If PCMR*a (pro port ra* rortality ratios) bad been calculated, -eative cancer would still be elevat- REFERENCES ' level of significance. Interest- Anderson HA, Snyder KS, Levinson T, Woo C, Lllis t, -h csncer was seen in the propor- Selikoff IJ (1978). Levels of CEA sarong vinyl chloride 'Xter and Fox (1976). and polyvinyl chloride exposed workers. Cancer 42:1560-1567. Anderson D, Richardson CR, Weight TH, Purchase 1FH, Adams WCF (1980). 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