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Environmental Health Perspectives Vol. 41, pp. HS-1S1. tSil Mortality and Cancer Rates among Workers in the Swedish PVC Processing Industry by Gustavo Molina*, Bo Holmberg*, Stig Elofsson*, Lars Holmlund,* Rein Moosing,* and Peter Westerholm** Personnel lists from four PVC-processing industries were collected on production of employees with at least three months of employment at the beginning of 1945 and the last day of employment December 31, 1974. Of 2073 persons, 103 could not be followed up, because they had moved abroad. The remaining persons comprise the cohort of 1970 individuals who were analyzed and compared with the national population with respect to mortality from various diseases and cancer morbidity. The death risk from myocardial infarction is elevated in the cohort. This elevation is most clearly apparent in the subcohort which had at least two years of exposure time and where the analysis was dirveted at circumstances chronologically close to the time of exposure. The myocardial infarction risk related to vinyl chloride exposure is discussed in relation to earlier studies on the vascular effects of vinyl chloride. An indication of an elevated risk of morbidity and mortality from tumors in the digestive organs is also present. However, this is not statistically confirmed. A few future follow-ups of the present study are necessary in order to clarify any possible elevated risk of tumors in the PVC-processing industry. Vinyl chloride has been shotTM to cause sclerodermia, Raynaud's phenomenon, acroosterolysis, liver damage and liver cancer (hemangiosarcoma) (2) in workers exposed to vinyl chloride monomer (VCM). This has been shown in studies (2, 3) performed at companies which fabricate poly(vinyl chloride) (PVC). In animal experimental studies it has been reported that inhalation of VCM causes malignant tumors in different organs in rodents U-6). In Sweden, in 1974, two cases of liver heman- Occupational Toxicology Unit, Department for Occupational Medicine, Labor Medicine Division, Department of Occupational Safety, Box 100, 26 Stockholm, Sweden. ^Statistical Institution, Stockholm University. Box 6701, 113 So Stockholm, Sweden. tGroup for Applied Statistics, Karlbergiv2gen S2, 113 35 Stockholm. Sweden. `Bureau of Statistics. Department of Welfare. 106 30 Stock holm, Sweden. * giosarcoma were diagnosed in employees at a company engaged in the processing of VCM and PVC (7). Later another two cases occurred at the same factory. Studies on other forms of cancer (8, 9> suggest that VCM-exposed workers in the PVC fabricating industries may possibly run an elevated risk of contracting forms of cancer other than hemangio sarcoma in the liver. Earlier, an excess mortal ity from cardiovascular diseases was also observed (10) in employees in the PVC manufacturing indus try. The present retrospective cohort study was per formed for the purpose of determining the pattern of morbidity and mortality in the PVC processing industry. The PVC processing industry, generally speaking, has had a lower level of exposur e to VCM than the fabrication industry. In the Swedish PVC processing industry, at present, about 5'> persons are employed in production. October 1981 21138001 145 BFG10760 Materia! and Methods earner man nu huvujh The two latter named study cohorts were chosen Information for the study was collected from four in order to study whether any differences existed in PVC processing companies. The four companies all the death cause pattern with respect to when the used PVC which, after additions of various chemi deaths occurred after the beginning of exposure. Cohort cals. is heat-treated for fabrication into floor cover- The first of the study cohorts was intended to shed ng. lace, pipes, and food packaging. light on possible causes of death which occur rela Exp. class Exp. class tively early , e.g., accidents caused by the job. The Exp. class Data Collection second was intended to shed light on such death causes as occurred after a longer time had passed. Exp. class The following data were collected from the per Tumors caused by occupational exposure, for ex sonnel lists at the companies: personal number, ample, often have a long latency period, 5-10 yr or name, beginning and end of exposure (year and longer. Table 4. i certain cr month) and class of exposure. least six In order for a person to be included in the original cohort, at least three months of employment was required in the period beginning in 1945 and the Results I ending December 13, 1974. The exposure was classified as follows: class 3 (high), work in the mixing department: class 2 (medium), heat treat ment machines; and class 1 (low), other production departments. The original cohort was relatively young at the beginning of exposure. The age distribution in the different exposure classes is given in Table 1. One finds various dissimilarities between the exposure classes. In class 1 (low), 41.7% were younger than Malignant Digestive Cardiovas, Myocardia Accidents. The collected data were transferred to punched cards and magnetic tape for statistical processing. The magnetic tape was coordinated with the na 35 years at the beginning of exposure; in class 2 (average), 47.7%; and in class 3 (high), 50.6%. There `Risk r:i than 10C1. tional total population and the so-called death tapes for the 1961-1975 period and checked against the Table 1. Age distribution in original cohort at beginning of exposure were ah cancer registry by the Central Bureau of Statistics with res (SCB). The personnel numbers which could not be % in each exposure class it shotil recovered at this time were checked by the national Age 1 2 3 1-3 which w taxation office. The original cohort included a total entranci of 2.073 persons. Of these, 103 persons (5%) dropped out, 70 or whom had moved abroad, 5 were found in the missing persons register of the tax office, and < 19 20-24 25-29 30-34 1.6 7.5 13.5 19.1 2.0 14.6 15.7 15.4 8.9 14.3 21.4 17.0 2.1 9.2 14.4 18.3 which rt times is 11 has long 2S could not be traced. Study Cohorts For the statistical processing, the results of the 35-39 40-44 45-49 50-54 55-59 60-64 17.0 13.7 11.1 8.0 5.1 2.6 13.2 10.7 15.9 [12.6 9.8 13.3 12.6 8.9 11.3 4.7.8 5.4 7.8 3.9 1.8 4.7 42.0 1.8 2.4 The c increase tional a' r. : the subj Study cohort of 1970 persons were divided into a number > 65 0.7 0.3 0.0 0.6 least six of subcohorts (study cohorts): (1) all persons with at least three months of exposure (follow-up time from the beginning'of exposure and through 1976); (2) all No. of persons 100% (1501) . 100% (357) 100% (112) 10%% (1970) t the risk what ret deaths i.- persons with at least six months of exposure ex :1 I cluding those who stopped before 1961 (follow-up time from beginning of exposure but no earlier than 1961 and through 1976); (3) all persons with at least Table 2. Distribution of exposure time in the original cohort. % in each exposure class 3) Table < six months of exposure and where the exposure Months 1 2 3 1-3 began no earlier -than 1961 (follow-up time from sn beginning of exposure and through 1976); (4) all persons with at least two years exposure (follow-up <5 6-23 24-59 13.1 -0.3 38.4 8.4 0.0 10.1 ii Cohort 8.9 31.3 A - -- 25.0 17.4 10.7 22.8 Exp. cbv* time from two years after beginning of exposure 60-119 15.3 45.7 15.2 20.8 34 Exp. clas but no earlier than 1961 and through 1976 but no > 120 8.2 28.3 65.2 15.1 Exp. cb-- Li more than ten years after exposure stopped); (5) all persons with at least two years exposure (follow-up i time from ten years after exposure began but no Li 146 100% 100% 100% 100% Of = 1510) (.1/ = 357) (V = 112) (V = 1970) "ii Environmental Health Perspectives Exp. etas `Risk <- Octobe re chosen e: `stedin v en the exposure, d to shed o. x rela_ b. The -,;ch death d massed, v for exj-iO yr or Table 3. Observ ed and anticipated number of deaths as of December 31, 1976. No. of deaths Cohort Number Observed Expected Ratio O/E Exp. class 1 Exp. class 2 Exp. class 3 1303 53 356 14 112 6 Exp. class 1-3 L. ! - 1171 73 Table 4. Observed and anticipated number of deaths from certain causes during the 1969-1976 period in those with at least six months of exposure including those who stopped before 1961.* 55.5 21.9 10.3 87.8 A 0.95 0.64 0.70 0.84 Approx. 95% confidence interval s 0.26 = 0.34 0.47 = 0.19 Ob Ex Ratio i' a! ; at the I' served pected O/E .iLh in the -.b!e 1. One epeposure i Malignant tumors 140-209 l. Digestive organ tumors 150-159 Cardiovascular diseases VII Myocardial infarction 410.90 17 14.0 1.21 8 4.9 1.G3 22 24.3 0.91 15 20.0 1.49 than & Accidents, suicide, etc. XVII 13 9.2 1.42 : m class 2 'rhere 1 f 'Risk calculated from the beginning of exposure but no earlier than 1961. Study cohort 2 (1771 persons). . Winning of f were also dissimilarities in the length of exposure i with respect to exposure class (Table 2). However, i it should be noted that the table includes cases ' ' 1-3 p 2.1 I 9.2 `-J 14.4 1S.3 r, 15.9 13.3 I 11.3 7.8 4.7 2.4 O.fi which were still under exposure at the final date for tc entrance into the cohort (December 31, 1974), for which reason, a certain bias toward short exposure times is found. Regardless of this, exposure class 3 has longer exposure times on the average. * The cohort as a whole reveals no noteworthy- increase in the total risk compared with the na tional average, nor is there any indication of this in the subgroups making up the study cohort. , Study cohort 1, which includes everyone with at least six months of exposure and with calculation of 10%% (1970) the risk from the beginning of exposure, is some what remarkable in that the anticipated number of deaths is significantly higher than that observed up Figure 1. Cumulative deaths (in percent): (V) observed; (V) anticipated. Expected value calculated from beginning of exposure. Study cohort 1 (1970 persons). The percentage for a given year was calculated as 100 (number of persons dying through year in question divided by the number of persons beginning exposure up to and including the year in question). to 1964 (Fig. 1). This is commented on further in the discussion. Study cohort 2 (Tables 3 and 4; Fig. 2) includes persons with at least six months of exposure, excluding those who stopped before 1961. The risk calculation is made from the beginning of the exposure, but no earlier than 1961 and up to the end of the follow-up time (1976). The observed number of deaths is somewhat lower than expect ed, much lower in exposure class 2. Classes 2 and 3 are relatively small and are sensitive to random deviations in this type of analysis. In order for random deviations not to influence the results, the classes were combined. This is true of all study cohorts. This distribution with respect to the vari- `"'cir.al cohort. 1-3 ~ioTT 31.3 ">.8 J.8 I- 15.1 I ioo% = 1570) ^bcctivcs Table 5. Observed and anticipated number of deaths as of December 3], 1976 in those with at least six months of exposure beginning no earlier than 1961.* Cohort Exp. class 1 Exp. class 2 Exp. class 3 Exp. class 1-3 Number 1139 247 42 1428 No. of deaths Observed Expected 43 41.2 4 11.7 1 1.8 43 54.7 Ratio O/E 1.04 0.34 0.83 Approx. 95% confidence interval = 0.31 = 0.34 r 0.35 'Risk calculation from beginning of exposure. Study cohort 3 (1428 persons). October 1981 21138003 nr BFG10762 deaths aoticlpsted mt mi mo mi Figure 2. Cumulative deaths (in percent). Expected value calculated through 1961. Study cohort 2 (1771 persons). Percentage for a given year calculated as in Fig. 1. */. death anticipated observed Figure 3. Cumulative deaths (in percent) of those who began exposure in 1960 or later. Study cohort 3 (1428 persons). Percentage for a given year calculated as in Fig. 1. oiu death causes is shown in Table 4. The observed and anticipated number ofdeaths during the 1961-1968 period is relatively small, only a few cases, and the death cause .classification was modified as mentioned earlier in 1969. for which reason 1961-1968 period is not discussed separately. By and large, the picture is the same there as for the 1969-1976 period re ported on. From Table 4, one sees that the observed number of deaths, especially those from tumors of the digestive tract, myocardial infarction and accidents, is somewhat higher than anticipated. However, the differences are not significant. Study o 100 so i * s i t i ton imms years after beginning of exposure Figure 4. Observed death risk per year at different points of time after beginning of exposure expressed in percent-of corresponding anticipated risk in those who began exposure in 1961 or later. Study cohort 3 (1428 persons). Table 6. Observed and anticipated number of deaths from certain causes during the 1969-1976'among those with at least six months of exposure beginning in 1961 or later.* Ob Ex Ratio served pected 0/E Malignant tumors 140-209 Digestive organ tumors 150-159 Cardiovascular diseases VII Myocardial infarction 410.90 Accidents, suicide, etc. XVII 9 9.7 0.93 4 3.3 1.20 16 16.2 0.99 14 11.2 1.25 11 7.3 1.51 `Risk calculated from the beginning of exposure. Study cohort 3 (1428 persons). cohort 3 (Tables 5 and 6; Figs. 3-5) which pertains to those who began working in 1961 or later but which otherwise satisfy the same criteria as study cohort 2, displays a similar picture. An analysis of study cohort 3 according to for mula B (Figs. 4 and 5) indicates that the annual risk during the first year of exposure is somewhat lower ( than the anticipated one, but that after about ten years, an increased risk occurs so that the observed risk becomes higher than the anticipated. Maligi-Jr Digi-ft-,;-., Carrii-.-. _ Mynca.-.. AcciO.-:. t.-_v. I 1 Table 7. Observed and anticipated number of deaths from certain causes during the 1969-1976 among those with at least two - years of exposure.* Observed Expected Ratio 0/E Malignant tumors 140-209 Digestive organ tuffiors 150-159 Cardiovascular diseases VII Mvocardial infarction 410.90 Accidents, suicide, etc. XVII 5 (9) 2 (4) 15 (16) 11 02) 4 (5) 7.4 (8.9) 2.6 (3.2) 12.7 (15.8) 5.4 (6.6) 4.6 (5.1) - 0.86b (1.01) 0.78b (1.27) 1.18b (1.01) 2.03b (1.82)b 0.87b (0.97) -w `Risk calculated from two years after beginning of exposure and no more than five years (10 years) after end of exposure. Study a,, cohort 4 (1155 persons). -St* bp < 0.05. 148 Environmental Health Perspective^ 21138004 Wi (Vetoil BFG10763 Table 8. Observed and anticipated number of deaths from l, certain causes during the 1968-1976 in those with at least two ! years of exposure.* i i: \:s after .*<nning <posure . :c.it points of in percent of . "n exposure ([Waths from :(i ,^ith at least tatio O/E Ob Ex Ratio served pected O/E Malignant tumors 140-209 9 6.0 1.51 Digestive organ tumors 150-159- 4 2.2 1.85 Cardiovascular diseases VII 12 11.1 1.08 [ Myocardial infarction 410.90 Accidents, suicide, etc. XVII 8 4.5 1.77 2 2.5 0.79 V Risk calculated from 10 years after beginning of exposure. Study cohort 5 (680 persons). 9 _ i Table 9. Observed and anticipated number of deaths from Il cancer during 1961-1976 in those with at least six months of exposure excluding those who slopped before 1981.* f: .V Ob- Ex- Ratio f served pected O/E Malignant tumors (total) Digestive organ tumors (150-159) 51 44.6 11 ' 8.5 1.14 1.29 r Risk calculated from beginning of exposure but no earlier than 1961. Study cohort 2 (1771 persons). ' No. of risks Figure 5. Cumulative survival probability (in percent) ofthose who began exposure in 1961 or later and have at least six months of exposure. Study cohort 3 (1428 persons). -1 ; 7 0.93 :.,3 1.20 1? t 0.99 !j 1 1.25 `-.J 1.51 t; "tudv cohort 'i t 1- 4'4* ') pertains c j later but ria as study ig to fornnual risk vhat lower about ten i I'observed ui at least two i :rt i: ; 'id : a?)i r.2)b V'^ure. Study In study cohort 4 (Table 7) which concerns time during ongoing exposure or a relatively short time after the end of exposure, i.e., "short-term per spective," one sees an increased death risk from myocardial infarction. Other causes are somewhat lower here than expected. In study cohort 5 (Table 8), finally, one finds an indication of an increase in the death risk as regards tumors, but also for myocardial infarction. The differences between the observed and anticipated numbers are not, however, statistically confirmed at the 57c level. The result with respect to mortality can be sum marized as follows. In the study cohorts, overall, one finds no noticeable increase in mortality. On the other hand, there are indications of a shift in the death cause pattern compared with the national average. This shift is expressed primarily in the fact that the number of myocardial infarctions is noticeably higher during ongoing exposure or within a relatively short period of time after the end of exposure. There are also indications that the death from tumors can be elevated among persons with a long latency period (Tables*7 and 8). In the question of cancer morbidity, there is no certain increase in study cohort 2 (Table 9 and Fig. 6). In the question of tumors of the digestive or gans, in the same study cohort, 11 cases were observed as opposed to an anticipated 8.5. The Figure 6. Cumulative rates of cases of all cancer (in percent). Study cohort 2 (1771 persons). The percentage for a given year was calculated as 100 (number of persons diagnosed through year in question divided by the number of persons beginning exposure through year in question). difference is not statistically verified. One of these eleven tumors was liver cancer (ICD 155.0). Discussion A noteworthy finding which arises in the analysis of the total cohort mortality (Fig. 1) is that the number of deaths at the beginning of the obseiwation period (1947-1964) is significantly lower than one would expect in relation to the national aver age. This difference is so great that one cannot directly consider it to be randomly conditioned, nor can it be entirely ascribed to the so-called healthy worker effect. Theoretically, of course, the possibil ity exists that the selected cohort, in the question of mortality and the factors which influence said mor tality, deviates from the general population. A more credible possibility is, however, that the personnel register that was available at the company involved at the time of this study was incomplete in the matter of hirings during this early period. A per sonnel register which, in the mid-1960's, was purged Orinhor IQST 21138005 BFG10764 .-of persons who began employment before 1960, factors. Among otner nsK iactore, one can aU could lead to the difference mentioned above. The name hereditary characteristics and high blood pr^_ companies involved reported that such a purging sure. In this connection, there is reason to recoil* did not occur, so far as they knew. that the causal network of coronary disease is mui' If such a purging (thinning out) nevertheless tifactorial and that the disease has an environmen- occurred, this would have resulted in the elimina tal relationship in the broad sense. There is al.*> tion of persons with a long observation time at the reason to recall the aspect that the total risk intime of follow-up. In the present study, the risk creases when several risk factors, known or un calculations were limited to beginning no earlier known, are allowed to collaborate (11, 12). than 1961. This means a limitation of the analysis to It has not been possible to establish the distribu. pertain to the group of employees who were living at the beginning of 1961 and where the risk of an tion of such already known risk factors for coronary disease in the cohorts studied with respect to the ( elimination is positively eliminated. This limitation, national population in general. Therefore, no con however, signifies a weakening of the analysis, tinued analysis of the matter of the causal relation since parts of the cohort with long follow-up times ship between close environment and heart disease are excluded. Basically, this weakening signifies a poorer possibility of discovering an elevated inci morbidity can be made within the limits of this study. ( dence of cancer if one exists. Exposure classes 2 and 3 constitute subcohorts The myocardial infarction mortality (ICD 410.90) that are too small, in the present study, to allow a is elevated in the cohort. This elevation occurs most meaningful discussion of the myocardial infarction clearly in the category of the total cohort which has risks relative to the various exposure levels in the {at least two years of employment time and where processing industry. In this connection, one should the analysis was directed at the period of time also consider the circumstance that the exposure following two years after the beginning of employ classes in this study are based on interviews with ment and extendi ,g to no more than five years after the employees directed at the work environment at the beginning of employment. Therefore, this in the time in question some 10 to 15 years ago. volves that fraction of the mortality from myocar Therefore, this involves an environment which has dial infarction which chronologically is relatively subsequently undergone changes. Objective classi closely connected to the time of employment. It is fication criteria in the matter of exposure, e.g., in impossible on the basis of such obseiwations to' the form of environmental measurements, do r.ei 1 draw conclusions that the.elevation was caused by exist. The distribution into exposure classes is, for exposure to vinyl chloride. The observed'increase this reason, fraught with uncertainty. in myocardial infarction mortality is, however, so In animal experiments, it has been found that the striking that it, in combination with the known - toxicity picture in rodents chronically exposed to facts about the toxic properties of vinyl chloride, VCM involves the blood vessels. Besides hermm- Ij must be given consideration. There are no reasons giosarcoma in the liver and the other organs (4, i> to assume that varying diagnostics, standards or the inhalation of VCM is also believed to cause ? practices in filling out the death certificates alone development of telangiectasis O) in the liver ofmice could provide an explanation. A natural conclusion which can lead to death from hemocoele. Changes is, therefore, that if one disregards the possibility in the sinus cells have been observed in liver biop of a random local phenomenon, the increased fre sies in VCM-exposed workers (13). Capillary changes quency is to be ascribed either to selection of indi in the skin of the Angel's have also been observed I .1 viduals susceptible to the risk or an outbreak of risk (14-16), both in VCM-exposed workers with other factors in the close environment of employees. A vascular-involved diseases, such as acroosteolvsis. combination of these two circumstances is, ofcourse, Raynaud's phenomenon, and sclerodermia, and in 1 also possible theoretically. VCM-exposed workers without such diseases. As In this connection, it should be noted that many over-representation of deaths from cardiovascular risk factors for myocardial Infarction are environ diseases has also been observed in a study on the mentally conditioned in the fact that they constitute PVC-fabricating industries (10). Animal experimen part of the lifestyle of the modern social environ tal and previous medical studies of VCM-exposed J ment in an industrialized country. Cigarette smok populations therefore support the assumption ing, physical inactivity, overweight and high blood the increased risk of myocardial infarction observe lipids constitute environmental factors which are in the present study could possibly be ascribed w J related to social behavior. It is a well known fact VCM exposure. that the risk of coronary vascular disease in the As regards the mortality and morbidity frora heart varies, inter alia, with the total load of risk tumors, the results are uncertain. There are certain :i! I> iiilitii ri.~ -.'I ri vl'tlt. .. ii -t I i : rili1 ' A.-.l U -tip :'Y. ;u :;!> t. .am* 150 Environmental Health Perspectives Ii.Ikt r.bu_ ?*vro:tary 3 * tlie t* con* irL.tionii! si ri:sease ' Js? tc this j rutv- ihorts A ; to :.!loW a Sal infarction t revel# in the spone should ^5 exposure tervicws with -.pi lent at '(\.*rs ago. which has iviive classif n*. e.g., in rl( its, do not classes is, for fr.Vi.dl that the ;U*xiposed to esiik s hemanrpjvans (4, 5) - ;<! to cause rr.'.er ofmice vie-. Changes i| ; iiver biop-i ary changes teen observed with other -- i-osteolysis, h.mia, and in n diseases. An < Miovascular Judy on the -r-i experimen} CM-exposed -f option that r- I bserved he - .Jibed to indications of an elevation, but the differences are not statistically confirmed. One can think of two possibilities here: (1) in reality, there is no increase in the risk of tumors; (2) there is indeed an' in creased risk of tumors. The results neither confirm nor refute this. Tumors do not occur until after a long latency period. The majority of the persons included in the study did not begin their exposure until the 60's and 70's and therefore could not be followed for a sufficiently Tong time. An accurate follow-up of the present cohort during the coming five-year period should bring greater clarity into this. In the present connection, it is of interest that in a recently published mortality study (17) on almost 4300 deaths in the American PVC-processing in dustry, an overrepresentation in cancer mortality appears to exist (all cancer), especially gastrointes tinal cancer in both sexes. REFERENCES 1. Holmberg, B., and Molina, G.: The industrial toxicology of vinyl chloride. A review. IVork-Environ. Health 11:138-144 (1974). 2. Creech, J. L., and Johnsson, M. N. Angiosarcoma of the liver in the manufacture of polyvinvl chloride. J. Occup. Med., 16: 150-151 (1974). 3. Lloyd, W. J. Angiosarcoma of the liver in vinyl chloride/ polyvinyl chloride workers. J. Occup. Med.. 17: 333-334 (1975). 4. Holmberg, B., Kronevi, T., and Wine!). M. The pathology of vinyl chloride exposed mice. Scand., 17: 328-342 (1976). 5. Maltoni, C. The value of predictive experimental bioassay in occupational and environmental carcinogenesis. An ex ample: vinyl chloride. Ambio, 4: 18-23 (1975). 6. Viola, P. L., Bigotti, A., and Caputo, A. Oncogenic response of rat skin, lungs, and bones to vinyl chloride. jbidity from ej-are certain 1 '`crspectives / | \ I i October 1981 Cancer Res., 31: 516-522 (1971). 7. Byren, D., and Holmberg, B. Two possible cases of angiosarcoma of the liver in a group of Swedish vinyl chloride-polyvinvl chloride workers. Ann. X.Y. Acad. Sci'.. 246:249-250 (1975). 8. Monson, R. R., Peters, J. M., and Johnsson. M. X. Proportional mortality among \invl chloride workers. Lan cet ii, 397-398 (1974). 9. Tabershaw, J. R., and Gaffey, W. R. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J. Occup. Med., 16: 509-5IS (1974). 10. Byren, D., Engholm. G., Englund, A., and W'esterholm. P. Mortality and cancer morbidity in a group of Swedish VCM and PVC production workers. Environ. Health Perspect. 17: 167-170 (1976). 11. RCP and BCS. Prevention of coronary heart disease. Report of joint working party of the Royal College of Physicians of London and the British Cardiac Society. J. Roy. Coll. Physicians, 10: 213-275 (1976). 12. Tibblin, G., Wilhelmsen, L., and Werke, .L. Risk factors for myocardial infarction and death due to ischemic hear, disease and other causes. Am. J. Cardiol. 35: 514-522 (1975). 13. Popper, H., and Thomas, L. B. Alteration of liver and spleen among workers exposed to vinvl chloride. Ann. N-Y. Acad. Sci.. 246: 172-193 (1975). 14. Marica, H., Johnsson, M. X., Whetstone, C. L., and Le Roy, E. C. Capillary abnormalities in polyvinyl chloride production workers. J. Am. Med. Assoc., 236: 1368-1371 (1976). 15. Marica, H., Johnsson, M. X., Whetstone.'.C. L., and Le Roy, E. D. In rivo capillary abnormalities in vinyl chloride workers. In: Microcirculation, Yol. 2. J. Grayson and W. Zingg, Eds., Plenum Press, Xew York, 1976. 16. Marica, H., Darke, C. S-, Archibald. R. M., and Le Roy. E. C. In vivo observations of skin capillaries in workers exposed to vinyl chloride. An English-American compari son. Brit. J. Ind. Nled., 35:1-7 (1975). 17. Chiazze, L., Xiefcols, W. E., and Wong. O. Mortality among emplovees of PVC fabricate-. J. Occup. Med.. 19: 623-628 (1977). 18. Chiang, C. L. Stochastic Processes in Biostatistics. An Introduction. Wilev, Xew York, 1971. BFG10766 151 excess of lung cancer (5 observed versus 1.98 expected.) Cancer of the Lymphatic and Hematopoietic System in Humans Table 4 summarizes data on cancer of the lym phatic and hematopoietic systems among workers exposed to VC. The relative risks for various studies ranged from 1.0 to 2.2, and none of the results demonstrated a significant excess. Although somewhat suggestive, the data need to be further analyzed by latency period and exposure levels combined. Analysis of data separately for lym phatic cancers and leukemia might also lead to meaningful observations. Summary In summary, epidemiologic evidence demonstrates that the carcinogenic effects of VC in humans extend beyond the liver. The brain and lung should also be considered target organs. Some studies indicate that the lymphatic and hematopoietic sys tems are also ir.rolved. These observations in humans are supported by studies demonstrating the induction of cancer of these same sites in experimental animals. REFERENCES 3. Patty, F. A., Yant, W. P., and Waite, C. P. Acute response of guinea pigs to vapors of some new commercial organic r compounds. Publ. Health Kepts. 45: 1963-1971 (1330). 2. Selikoff. I. J, and Hammond, E. C., Eds. Toxicity of vinyl chloride-polwinvl chloride. Ann. N.Y. Acad. Sci. 246:1337 (1975). ' 3. Viola. P. L.. Biogotti. A., and Caputo, A. Oncogenic responses of rat skin, lungs, and bones to vinyl chloride. Cancer P.es. 31: 516-519 (1971). 4. Maltoni. C.. Lefemine. G., Ciliberti, A., Cotti, G. and Carrttti. D. Carcinogenicity bioassays of vinyl chloride monomer. A mode! of risk assessment on experimental bases. Environ. Health Perspect. 41: 3-29 (1981). 5. Waxweiler, R. J.. Stringer. \V., Wagoner, J. K., Jones. J., Falk. H.. and Carter. C. Neoplastic risk among workers exposed to vinvl chloride. Ann N.Y. Acad. Sci. 271: 40-48 (1976). 6. Byren. D., Engholm. G.. Englund, A., and Westerholm-, P. Mortality and cancer morbidity in a group of Swedish VCM and PYC production workers. Environ. Health Perspect. 17: 167-170 (1976). 7. Fox. A. J., and Collier, P. F. Mortality experience of workers exposed to vinyl chloride monomer in the manufac ture of poivvinv! chloride in Great Britain. Brit. J. Ind. Med. 34: 1-10 (1977). 8. Monson. R. R., Peters. J. M., and Johnson, M. N. Propor tional mortality among vinvl-chloride workers. Lancet ii: 397-395 (1974). 9. Tabershaw, I. R., and Gaffey, W. R. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J. Occup. Med. 16: 509-518 (1974). 10. Buffler, P. A., Wood. S., Eifter, C., Suarez, L., and Kilian, D.' J. Mortality experience of workers in a vinyl chloride monomer production pJant. J. Occup. Med. 21; 195-203 (1979). 11. Ott, M. G.. Langner. R. R. and Holder, B. B. Vinyl chloride exposure in a controlled industrial environment. A long- term mortality experience in 594 employees. Arch. Environ. Health 30: 333-339 (1975). 12. Equitable Environmental Health. Epidemiological study of vinyl chloride workers. Prepared for Manufacturing Chemists Association. 1978. f l y 1 | L r j' , x j -t il ^ J I if y I ii I * Ge Vin by \ Vinyl The i dardi/.e exposei West C study t chemic; tributio VCM a worker: The studv. the YCl plants t Table three c Austria insuftici tionals mine th man mt total Hf years h: S!H.vinc :> rale years tr. ir.g the J I* CKidxl 94 Environmental Health Perspecti 2113800$