Document 2jvz18aXRkKQ9EXzO7zJ581rb

R&S 001507 Environmental Health. Perspectives Vol. 41. pp 95-99, 1981 German Investigations on Morbidity and Mortality of Workers Exposed to Vinyl Chloride by H. Weber,* W. Reinl,* and E. Greiserf Two studies on mortality and morbidity of workers exposed to vinyl chloride monomer (VCM) which have been carried out on behalf of the Ministry of Labour, Health and Social Affairs on Northrhine-Westphalia are reported. Vinyl Chloride Mortality Study The aims of this study were to determine stan dardized mortality ratios (SMR) for male workers exposed to VCM, using the mortality rates of the West German male population as reference, to study the SMRs of a cohort of workers of the chemical industry comparable concerning age dis tribution and observation period but not exposed to VCM and to determine the SMR of a cohort of workers in PVC-processing plants. The study was designed as a historic cohort study, covering the period from the beginning of the VCM- and PVC-production in all of the German plants till the end of 1974. Table 1 shows the main characteristics of the three cohorts investigated. Only Germans and Austrians were included in data analysis because of insufficient mortality data on various foreign na tionals employed in German factories. To deter mine the mortality rates of Austrians, West Ger man rates were used. To calculate expectations of total mortality, the mortality rates of the adequate years have been used. To calculate expectations of specific causes of death for all years before 19G8, the rates of 1968 have been used; for the following years the rates of the corresponding years. Follow ing the procedure applied by Tabershaw (1), 'Staatlicher Gewerbearzt. Dusseklorf, W. Germany. * Diabetes Research Institute at the University of Dusseklorf. Division of Medical Statistics and Epidemiology, Dusseklorf, W. Germany. October 1981 weighting of observed cases of specific causes of death according to unknown causes of death has been done with weighting factors calculated sepa rately for three observation periods (up to 1959, 1960-1969, 1970-1974) as well as for six age groups. In all of the cohorts, follow-up rates have been near or above 90%. The percentage of causes of death that could not be investigated due to loss or deletion of death certificates varied from 7.3% to 13.1%. To calculate age-standardized mortality ratios of specific causes of death, weighting has been done according to the procedure used by Tabershaw and Gaffey (1) to compensate for unknown or unidentified causes of death. Table 2 displays total mortality as well as some of the relevant specific causes of death. It can be observed that the otherwise observed "healthy worker effect" cannot be demonstrated in the German cohorts exposed to VCM or employed in PVC-processing plants. In the VCM cohort there are significant eleva tions of SMR of malignancies of the lymphatic and hematopoietic tissues (ICM 200-209), and of malig nancies of the GI tract (ICD 150-159). The latter is due to the paramount elevation of SM R of tumors of the liver (ICD 155). It must be noted that there is a modest elevation of SMR of tumors of the liver also in the cohort not exposed to VCM nor employed in PVC-processing plants. No obvious explanation for this observation can be offered. In addition elevated SMRs for ischemic heart disease (ICD 410-414) can be found in all of the three cohorts. Due to methodological 95 * ii 80S 100 S *H shortcomings of the study no assessment of cardio vascular risk factors has been made. Therefore these results are of minor interest. When subdividing the VCM-exposed cohort ac cording to time of exposure there is a clear-cut increase of the SMR of liver tumors with time (Table 3). This seems to be highly suggestive of a time-response pattern. As it has been impossible to determine concentrations of VCM retrospectively due to technological and methodological problems, no dose-response pattern can be established. How ever time of exposure seems to be the best avail able guess for dose. Subclassification according to observation period Table 1. Characteristics of study cohorts. Group I, VCM'PVC production Group II, reference group Population (Germans + Austrians) Man years Follow-up completed till 12/31/74, 9c deceased Observed Expected Unknown causes of death No. 9c Total mortality (SMR) Foreigners (excluding Austrians) Deceased 7.021 73.734 93.2 414 435 30 7.3 95 882 0 4.910 76.029 S9.S 417 533 47 11.3 78 711 G Group III, PVC processing 4.007 52.S96 92.1 360 380 47 13.1 95 1.454 10 I i / / Table 2. Standardized mortality ratios. ICD 8 Cause of death VCM'PVC production Obs. SMR Total mortality 414 95 140-209 All malignant tumors 94 112 140-199 Malignant tumors of organs 79 103 200-209 Malignancies of lymphatic and hematopoetic tissues 15 214b 150-159 Malignant tumors of GI tract and peritoneum 45 149" 155 Malignant tumors of the liver 191 Malignant tumors of the brain 12 1523b 2 162 410-414 Ischemic heart disease 91 127" 410 Acute myocardial 66 114 800-949 Accidents 61 CO "Bevond 959c confidence interval (2). bBeyond 99% confidence interval (2). Reference group Obs. SMR 417 78 83 83 77 83 6 77 27 71 4 401" 2 184 115 131" 83 120 44 99 PVC processing Obs. SMR 3G0 95 62 So 60 S9 0 34 15 56 3 434 5 535" 96 158b 69 143b 32 110 Table 3. Standardized mortality ratios by duration of exposure. ICD 8 Cause of death < 12 Obs. SMR Duration of exposure, months 13-16 61--120 Obs. SMR Obs. SMR > 121 Obs. SMR Total mortality 140-199 200-209 150-159 155 191 Malignant tumors of organs Malignancies of lymphatic and hematopoetic tissues Malignant tumors of GI tract and peritoneum Malignant tumors of the liver Malignant tumors of the brain 53 6 1 3 0 0 93 13S 102 93 87 130 96 74 20 88 22 116 31 115 92 4 186 5 287 5 249 101 12 135 13 173 17 158 - 2 874" 3 1525b 7 252Sb 0- 1 350 1 278 96 Environmental Health Perspectives lV. ' i \ V ICD { 140-1 200-2 150-1 155 191 'Be bB< ICD: Total mort; 140-1 200--; 50-1 155 191 'B. bB Tab! Grou aT A-1I B-I B-1I Cc--nI D-l D-II *1 Oc 0 V / v i Table 4. Standardized mortality ratios by period of observation. ICD 8 Cause of death 140-199 200-209 150-159 155 191 Malignant tumors Malignancies of lymphatic and hematopoetic tissues Malignant tumors of GI tract and peritoneum Malignant tumors of the liver Malignant tumors of the brain "Beyond 95% confidence interval. bBeyond 99% confidence interval. To 1959 Obs SMR 12 160 1 147 8 270" 1 1282 1 oo i Observation period 1960-69 1970-74 Obs. SMR Obs. SMR Total Obs. SMR 29 84 194 103 414 95 9 275b 13 94 3 - 834" 0" 5 168 15 214b 24 177b 45 149" 8 2264b 12 1523b 1 223 2 162 Table 5. Standardized mortality ratios bj age. ICD 8 Cause of death Age group 24 25-34 35--44 45-54 55-64 3= 65 Total ' 1 Obs. SMR Obs. SMR Obs. SMR Obs. SMR Obs. SMR Obs. SMR Obs. SMR Total mortality 10 68 45 111 65 104 90 101 105 SO 90 103 414 95 140-199 Malignant tumors of organs 0 4 141 13 1S8" 19 141 22 76 21 100 79 103 200-209 Malignancies of lymphatic and hematopoetic tissues 0 2 194 4 303 4 264 3 162 2 197 15 214b 150-159 Malignant tumors of GI tract and peritoneum 0 3 397 10 3G5b 10 145 10 89 12 140 45 149b 155 Malignant tumors of the liver 00 6 6S65b 0 3 934b 3 1664* 12 1523b 191 Malignant tumors of the brain 0 0- 0 1 254 1 362 0 2 162 "Beyond 95% confidence interval. bBeyond 99% confidence interval. ''Ii i j I 30 C/5 o o CJ1 o to Table fi. Groups for subdivision of laboratory examinations. - Group Specification Table 8. Bromsulfalcin retention," AM AMI B-I B-1I CM Ife, CMI DM DM1 VCM/PVC production PVC processing VCM/PVC production and PVC processing, work capacity loss < 20% VCM'PVC production and PVC processing, work capacity loss 20% Germans and Austrians Foreigners (Exd. Austrians) Plants with high morbidity Plants with low morbidity Germans and Austrians Foreigners Retention normal Retention abnormal Total 17 30 33 21 50 51 "Chi square, = 6.25 (p < 2.5%). Total 47 55 101 Table 7. Bromsulfalcin retention." i VCM/PVC PVC Production Processing Total Retention normal Retention abnormal Total 26 21 47 44 10 54 70 31 101 "Chi square, = 8.09 (p < 1%). October 19S1 Table 9. Bromsulfalcin retention." Work capa Work capa city loss city loss < 20% > 20% Total Retention normal Retention abnormal Total 41 G 47 32 22 54 73 28 101 "Chi square, = 9.81 (p < 1%). 97 (Table 4) reveals a rather inconsistent pattern: malignancies of the lymphatic tissues (ICD 200-209) are significantly elevated in the sixties only, whereas SMRs for tumors of the liver increase till the end of the study period. This might be referred to differ ent latency periods for both kinds of malignancies, but other causes might likewise have contributed to these results. However, it has to be reported that the number of angiosarcomas confirmed histologi cally in the Federal Republic of Germany in pa tients previously exposed to VCM has actually come to 17 in contrast to mere 4 at the endpoint of the mortality study (12/31/1974). The distribution of SMRs by age (Table 5) demonstrates an obvious susceptibility of males aged 35-44 for malignancies in general as well as for malignancies of the liver. The data base for the German morbidity study consists of all of the reports of suspected cases of occupational disease due to VCM or PVC produc tion or PVC processing. The reference population for these reports has to be defined as the total NORMAL < 120 MG/DL PATHOL. > 120 MG/DL MG/0L NORMAL < 1.0 PATHOL. > 1.0 WORK CAPACITY LOSS <M WORK CAPACITY LOSS ^ 20 % Figche 2. Vinyl chloride morbidity study: oral glucose toler ance test, 120 min after loading (normal 120 mg/dl). R&S 001510 WORK CAPACITY LOSS < 20 i WORK CAPACITY LOSS > 20 * Ficcke 1. Vinyl chloride morbidity study: total bilirubin (nor mal 1.0). 98 WORK CAPACITY LOSS < 20 "A WORK CAPACITY LOSS 20 V Figure 3. Vinyl chloride morbidity study: reticulocytes (nor mal 15%). Environmental Health Perspectives MG/DL MG/DI * ON G S working population in 1974 in the above mentioned nationality (Table 8) and most pronounced when { branches, i.e., 6,500 workers in VCM or PVC subdividing by extent of work capacity loss (Table production and 42,800 workers in PVC processing 9). This latter result, however, must be expected (as given by the German Association of Plastic when an effect of exposure on liver function is Producing Industries). Till the end of 1974, 269 anticipated. An impairment of the excretory liver reports of suspected cases of occupational disease function is suggested by elevated total bilirubin had been received. As there has been no consistent values in the subgroup with work capacity loss , set of examinations performed on each of the cases, greater than 20% (Fig. 1). There seems to be an numbers of observations for various variables ana impaired glucose tolerance in this group, although lyzed vary according to examination method per- observed in a-small subsample only (Fig. 2), as well , formed. Insofar as the results of this study are of as a lower number of reticulocytes (Fig. 3). The much lower validity than those of the mortality thromocyte count in both groups was the same. study, one should regard them as hints for further These results, however, lead to no sensible inter [ investigations. pretation, as all results attempts failed to standard */ Four attempts to subclassify observation on the ize the methods applied for thrombocyte counts by 269 cases have been undertaken (Table 6). Only various laboratories. I those results showing significant differences when applying (-tests or chi-square tests are so classified. Amazingly none of the more sensitive lab examina tions of liver functions showed a marked difference REFERENCES ;' in all of the subclassifications besides bromsulfalein 1. Tabershaw, I. R., and Gaffey, W, R. Mortality study of ' retention. In this instance there is a significant workers in the manufacture of vinyl chloride and its poly mers. J. Occup. Med. 1G: 509-51S (1*97-1). difference when subdividing by VCM/PVC produc- 2. Bailar, J. C. Significance factors for the ratio of a Poisson tion versus processing (Table 7), as well as by variable to its expectation. Biometrics 20: 639-643 (1964), .oler i j 1 I 1' < T<k October 1981 33 99 U) o o --j. cn 99