Document nLg7Jw2gLbK3Q8GxoK9vrMm1

*5- ><*>3-1971 (1930). ; 3. Toxicity of via-. Acad. Sci. 246:13j- Environmental Health Perspectives Vol. hi, pp. 95-99, 1981 i Caputo, A. Oncogen i bones to vinyl chloric ;V berti, A., Cotti, G. ^ `assays of vinyl chlorij ssment on experitnoJ, German Investigations on Morbidity and41: 3-29 (1981). |f Vagoner, J. K., JonesX Mortality of Workers Exposed tostic risk among workfc Y. Acad. Sd. 271: 4$$ Vinyl Chloride. A., and Westerhoka,^ a group of Swedish VCli viron. Health Persjwt Mortality experienced by H. Weber,* W. Reinl,* and E. Greiser* tonomer in the manuf*. t Britain. Brit. J. Ini Johnson, M. N. Properide workers. Lancet i 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. R. mortality study ef "inyl chloride and id .8 (1974). Suarez, L., and KniTM. -:ers in a vinyl chloride :up. Med. 21: 19MB -r, B. B. Vinyl chkndr environment. A "'s. Arch. Enviroa Jg )*- ..uological study if Manufacturing Che Vin 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 `Vest German male population as reference, to <:udy the SMRs of a cohort of workers of the ,-hemical industry comparable concerning age dis tribution and observation period but not exposed to VCM and to determine the SMR of a cohort of *orkev in PVC-processing plants. The .dy 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-nine the mortality rates of Austrians, West Ger man ra* - -ere used. To calculate expectations of total m . --icy, the mortality rates of the adequate years have been used. To calculate expectations of specific causes of death for all years before 1968, the rates of 1968 have been used; for the following years the rates of the corresponding years. Followthe procedure applied by Tabershaw (1), .vtaatlicher Gewerbearzt, Diisseldorf. W. Germany. . Uube'.Ms p.search Institute at the University of Diisseldorf. ' -al Statistics and Epidemiology, Diisseldorf, 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 (2) 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 SMR 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 October 1981 95 21137001 BFG10755  * ! ' ^ *W ! 1 i i 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) determine concentrations of VCM retrospective) due to technological and methodological problei^ no dose-response pattern can be established. Hov ever time of exposure seems to be the best avai able guess for dose. 4 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, % deceased Observed Expected Unknown causes of death No. % Total mortality (SMR) 7.021 73.734 93.2 414 435 30 7.3 95 4.910 76.029 89.8 417 533 47 11.3 78 ..y. S CO 3 `f A 1 Group III, PVC 4 processing 'j > 4.007 52.896 92.1 380 (i 47 13.1 95 Foreigners (excluding Austrians) Deceased 882 711 66 1.454 10 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 12 1523b 191 Malignant tumors of the brain 2 162 4HW14 Ischemic heart disease 91 127* 410 Acute myocardial 66 114 800-949 Accidents 61 137* "Beyond 95% confidence interval (2). bBeyond 99% confidence interval (9). 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 : 360 95 ; 62 85 60 89 . 2 34 15 _ . _ 56 - 3 434 5 535* 96 15Sb 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 93 138 102 93 74 20 88 22 92 4 186 5 101 12 135 13 - 2 874* 3 -- 0-- 1 87 116 287 173 1525b 350 130 31 5 17 7 1 96 115 249 158 2528b < 278 96 Environmental Health Perspectives 21137002 BFG10756 fl n impossible to retrospectively problems, -~...,ned. Howthe best avafl- irvation perio| % roup III, PVC .V processing ^ 4.007 52.896 92.1 360 380 4 i 47 13.1 95 1.454 10 PVC processing Obs. SMR ' 0 95 i 62 85 60 89 ; 2 34 V 15 56 3 434 .? 5 535* r 96 i58b; 69 143s; 32 no * s *> 121 T. Obs. SMR.': 130 16 31 7 5 J 17 5s 7 50 1 h 96 .' 115 249 ' 158 2528Sr. 278 i: h Perspectives.. IC- 8 Cause of death Table 4. Standardized mortality ratios by period of observation. To 1959 Obs. SMR Observation period 1960-69 1970-74 Obs. SMR Obs. SMR Total Obs. SMR 140-199 >00-209 150-159 155 191 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 12 160 29 84 194 103 414 95 1 147 9 275b 5 168 15 214b 8 270* 13 94 24 177b 45 149* 1 1282 1 557 3 834* 0 8 2264b 12 1523b 1 223 2 162 Beyond 95% confidence interval. bBevond 99% confidence interval. Table 5. Standardized mortality ratios by age. 1CD 8 Cause of death Age group 24 25-34 35-44 45-54 55-64 s 65 Total 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 80 90 103 414 95 140-199 Malignant tumors of organs 0 4 141 13 188* 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 U .59 Malignant tumors of GI tract and peritoneum 0 3 397 10 365b 10 145 10 89 12 140 45 149b 155 Malignant tumors of the liver 0 0- 6 6865b 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. Table 6. Groups for subdivision of laboratory examinations. G:. o Specification A-1 VCM/PVC production A-11 PVC processing B-l VCM/PVC production and PVC processing, work capacity loss < 20% B-I! VCM/PVC production and PVC processing, work capacity loss * 20% C-l Germans and Austrians C-II Foreigners (Excl. Austrians) D-I Plants with high morbidity D-II Plants with low morbidity Table 7. Bromsulfalein retention.* VCM/PVC PVC Production Processing , Retention normal Retention abnormal Total 26 21 44 10 70 31 "Chi squaret = 8.09 (p < 1%). Cc.ober 1981 Total 47 54 101 Table 8. Bromsulfalein retention.* 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 9. Bromsulfalein retention.* Work capa- Work capacity loss city loss < 20% > 20% Retention normal Retention abnormal Total 41 6 32 22 73 28 "Chi square] = 9.81 (p < 1%). Total 47 54 101 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 MG/DL normal < 1.0 PATHOL. > 1.0 WORK CAPACITY LOSS <20 * WORK CAPACITY LOSS 20 % Figure 2. Vinyl chloride morbidity study: oral glucose toll anee test, 120 min after loading (normal 120 mg/dl). AND PVC PROCESSING WORK CAPACITY LOSS < 20 % ANO PVC PROCESSING WORK CAPACITY LOSS >20 * Figure 1. Vinyl chloride morbidity study: total bilirubin (nor mal 1.0). 98 AND PVC fROCESSING WORK CAPACITY LOSS < 20 % AND PVC PROCESSING WORK CAPACITY LOSS 20 % Figure 3. Vinyl chloride morbidity study: reticulocytes (m mal 15%). Environmental Health Perspective 21137004 BFG10758 1 Al < 120 MG/Ol 1 " VMcmii P<5 * VC PRODUCTION 'C PROCESSING CAPACITY tOSS .* ral glucose toler-' 0 mg/dl). working population in 1974 in the above mentioned branches, i.e., 6,500 workers in VCM or PVC production and 42,800 workers in PVC processing (a. iven by the German Association of Plastic Producing Industries). Till the end of 1974, 269 reports of suspected cases of occupational disease had been received. As there has been no consistent set of examinations performed on each of the cases, numbers of observations for various variables ana lyzed vary according to examination method per formed. Insofar as the results of this study are of much lower validity than those of the mortality study, one should regard them as hints for further in stigations. i jur attempts to subclassify observation on the 269 cases have been undertaken (Table 6). Only those results showing significant differences when applying f-tests or chi-square tests are so classified. Amazingly none of the more sensitive lab examina tions of liver functions showed a marked difference in all of the subclassifications besides bromsulfalein retention. In this instance there is a significant difference when subdividing by VCM/PVC productic - versus processing (Table 7), as well as by nationality (Table 8) and most pronounced when subdividing by extent of work capacity loss (Table 9). This latter result, however, must be expected when an effect of exposure on liver function is anticipated. An impairment of the excretory liver function is suggested by elevated total bilirubin values in the subgroup with work capacity loss greater than 20% (Fig. 1). There seems to be an impaired glucose tolerance in this group, although observed in a small subsample only (Fig. 2), as well as a lower number of reticulocytes (Fig. 3). The thromocyte count in both groups was the same. These results, however, lead to no sensible inter pretation, as all results attempts failed to standard ize the methods applied for thrombocyte counts by various laboratories. REFERENCES 1. Tabershaw, I. R., and Gaffey, tV. R. Mortality study of workers in the manufacture of vinyl chloride and its poly mers. J. Occup. Med. 16: 509-518 (1974). 2. Bailar, J. C. Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 20: 639-643 (1964).