Document ymyqyZG9V5387bZG9JXrMKdgD

FOR DU PONT USE ONLY Zentralbl. Arbeitsmed. Arbeits schutz. 32, no.2:44-62 (1982) NOTICE This material may be protected by copyright law (Title 17 U.S. Code). TRANSLATION VINYL CHLORIDE EXPOSURE AND MORTALITY OF GERMAN'CHEMICAL INDUSTRY WORKERS COMPARED TO THE MORTALITY OF NON-EXPOSED CHEMICAL INDUSTRY WORKERS AND PVC WORKERS E. Greiser, W. Reinl, H. Weber 1. Introduction In 197** i Creech and Johnson reported their observations on three hemangiosarcomas of the liver in workers of the US polyvinyl chloride (PVC) industry* In the same year, two cases of liver angio sarcoma were determined in a PVC plant in West Germany. Meanwhile, 18 workers of the PVC industry in West Germany have died asiresult of this disease, another patient with hemangiosarcoma of the liver is still alive. Worldwide 85 cases were reported up to May 1980 (information on the occurrence of, this disease in the USSR and in China is, however,not available). The results of animal experiment investigations by Viola et al (1971) and Maltoni et al (197*0 indicated a carcinogenic potential of vinyl chloride monomer (VCM) These investigations demonstrated the occurrence of malignomas in various organs and in rats, among other, the presence of liver angiosarcomas already at relatively low concentration of the breathed-in air. Finally, since 1972, 165 cases of disease as a result of VCM had been reported in the Federal Republic of Germany. Until September 30, 1980, this number had increased to 320 of which 106 cases were acknowledged to be work-related. These findings justify an epidemiological investigation to explain a disease and mortality risk in workers of the chemical industry possibly produced by exposure to VCM. The investigations described in the following were instigated by the Minister for Work, Health and Social well-being of NordrheinWestfalen in agreement with the Federal Minister for Work and Social well-being and the Professional Organization of the Chemical Industry. The investigations were conducted in cooperation with company physicians of the related companies. SAL 000070602 -3- It was not possible to include a parameter for the intensity of the exposure in the investigation since continuous measurements of the VC concentration in the work place are of a recent date and an auxiliary usable variable to estimate the concentration was not available* Before 1972, sufficiently sensitive methods for systematic measurements in most plants were not available. Aside from this, the measurements were first conducted for protection- against ex plosion. The data acquisition took place on uniform data sheets by the company physicians of the individual plants. To process this work, inexperienced personnel was used which first led to a number of documentation errors which could be rectified by repeated checking. The authorized registration offices provided the addresses resp. place of death for workers who left work in the plant before December 31, 1974. . The death certificate had to be obtained via the authorized health department for deceased workers. To an extent, this was difficult since in some health departments death certificates are destroyed 5 years after death as permitted by law. In these cases, an effort was made to determine the cause of death in a different manner, for example, through the attending physician. In other cases, the evaluation of available death certificates first appeared impossible since according to a correct interpretation of the Federal Statistics Law, some health departments treat the medical part of the death certificate as confidential. As a result of the intervention by the Minister for Work, Health and Social well-being of Nordrhein-Westfalen, an evaluation of these documents with correct linkage was possible while main taining partial anonymity. The causes of death were processed under observation of the signed regulations of the International Classifica tion of Diseases 8. This method was also used for causes of death when death occurred before 1968. For the total mortality and some specific causes of death, mortality rates for the male population of the Federal Republic were calculated in age classifications of five years. In order to determine a mortality risk in a certain population in one calendar year, two data are needed* the size of the population, in other words, the number of people who might have died in that year (= population at risk) and the number of people who actually died in that year. By dividing the number of deceased people by the number of all people, the mortality risk is obtained. Since the mortality risk differs in various age groups and generations, the risks are determined separately according to generations in five year age classes. A method for analyzing the suspected higher mortality which might have been caused by a chemical substance re sides in comparing the mortality risk of one group of people (cohort) SAL 000070604 -4- exposed to this substance with the mortality risk of the entire population. This comparison can of course only be made between the corresponding age groups of the total population and the in vestigated cohorts. Since the mortality risk changes over the years, such a comparison must also take place by calendar year. For example, when it is known from the mortality statistics of the total population that in 1968 from the age class of 30 to 35 year old men, 8 of 1000 died of a certain cause of death and the cohorts to be investigated in the corresponding age class for the total year comprised 500 men, it could be expected that 4 of these 500 men would have died during the year of the same cause of death when the mortality risk would be identical to the risk of the total population. The number of deaths to be expected is called "expectation value". In order to determine the expectation value, it must first be determined how many people in the related year were included in the appropriate age class, for example, the class of 30 to 35 y?ar oil men (= person years). If it is demonstrated that the death of more people was observed (= observation value) than could be expected by assuming an identical risk, the mortality risk is in creased. The standardized mortality risk (SMR) expresses the level of the mortality risk of the investigated cohorts compared to the same age population (risk = 100). An SMR of 130, therefore, shows a 30 % increased risk compared to the total population. In order to calculate the person years in five year age classes, only German and Austrian nationality workers were used from the worker population since cause of death statistics of other European nations were not available in sufficient detail. The determination of cause of death in these countries, moreover, appeared to be difficult for organizational reasons. Expectation values for the total mortality in the individual age classes were calculated based on the mortality rates of the corresponding calendar years. For the specific mortality rates, the rates of 1968 were used for all calendar years up to 1968, for all later calendar years, however, the rates of the corresponding years since encoding of the causes of death in the Federal Republic before 1966 was not conducted accord ing to the International Classification of Diseases and Causes of Death (ICD) but according to a specific German system (DAS). This procedure for causes of death with a rising tendency could have led to an overestimation of the expectation values for 1968 and con sequently, too tendential, to low standardized mortality rates (SMR). This procedure seemed,however, justified since otherwise a com parability of the SMR from later years would have caused problems. In order to consider the percentage of deaths having causes of death which could no longer be established in the calculation of the SMR for specific causes of death, the observed cases having specific causes of death were weighted analogously to the percentage of un explainable causes of death to all causes of death. 0 -2- Since the intent in this case was not the explanation of the possibly increased risk of a single disease (hemangiosarcoma of the liver) but the suspicion that an increased tumor risk existed, the possibility of conducting a case-control study was eliminated in advance* Such a study in view of the extreme rarity of angio sarcomas of the liver and the problems of a correct diagnosis of this disease would most likely not have been possible in a method ical and probelm-free manner. Therefore, the method of the historically prospective cohort study was selected. In this epidemiological stype of study, a group of people (cohort) which can be clearly defined by a common characteristic (in this case* exposure to VCM) is followed in their fate from a point in time in the past to a defined final point. The disease resp. mortality risk of these cohorts is then compared to the corresponding risk of a comparison group (most times the entire population) Since usable data sources for the evaluation of the disease risk of the population in West Germany are not yet available, the investigation was limited to a mortality study. Within the framework of our investigation, three cohorts of workers with their mortality risks were analyzed. 1. All workers who had been or still sure .involved in the production of VCM resp. PVC in the Federal Republic of Germany (7,021 workers of German and Austrian nationality). 2. A cohort of 4,910 workers of German and Austrian nationality from the same factories of the chemical industry without contact with VCM. 3. A cohort of 3943 workers of German and Austrian nationality from two PVC processing plants. 2. Material and Methods 1. Vinyl chloride mortality study Data of. all workers who were involved or still are in the 11 vinyl chloride (VCM) resp. polyvinyl chloride (PVC) producing plants in the Federal Republic of Germany up to December 31* 1984 were collected. The following data were secured for each individual worker* three initial letters of first and last name, date of birth, nationality, first date of employment, date of first exposure to VCM,, date of last exposure to VCM, last date of employment, last date the worker with certainty was still alive date of death for deceased workers. o,ov <0& -5- Weighting factors were separately calculated for six age classes and three observation periods (Table- 1.1 to Table 1.3). A similar method was used by Tabershaw. It is presupposed in this method that the unexplainable causes of death - if been explainable contained the specific causes of death in the same distribution as the explained causes of death, in other words, if 30 % myocardinal infarctions are found among the explained causes of death, the percentage of myocardinal infarctions among the unexplained causes of death also would have been 30%. Exceeding the 95 % resp. 99 % confidence interval was examined for the calculated SMR (Bailar, 1964). 2. Mortality study of workers in the chemical industry who were not exposed to VC From seven plants of the chemical industry, the data of 4,910 male workers were acquired, who in their total structure could be compared with the group exposed to VC but who had not been exposed to VC nor PVC processing. The acquisition methods for this comflasrison group were identical except for the data on first and last exposure omitted in this case. '3. Mortality study of workers of PVC processing plants Analogous to the method illustrated under 1, the data of workers from two plants were acquired and processed who had been involved in PVC processing, therefore, in general exposed in any case to a very slight VC concentration. This study in the analysis only included the data of German and Autrian workers. 3. Results 3.1 Basic data Cohort 1 of the workers of the chemical industry exposed to VCM (7,021) could have included almost all workers who were exposed to VCM at one time or another. A comparable complete inclusion for the other cohorts of the study (cohorts 2 - workers not exposed to VCM, cohorts 3 - workers from PVC processing) could not be attained. A comparison of the basic data of these cohorts shows that workers exposed to VCM with an average observation period of 10.5 years could be observed for this study for a considerably shorter period than the cohorts of the unexposed workers (15*5 years ob servation period) or the cohorts of the workers from PVC processing with 13.2 years (calculated from Table 2). SAL 000070606 6- - bl. Arbeiismed. 32 (1982) 2 I'inylchlorid-Zxpasiiion u. Mortalitfit ________47 Table 1. Weighting factors for specific causes of death for the calTab. 1 Gewichtungslaktoren fur spezilische Todesursachen zur Berechnung der SMR CUlation Of SMR - Altersgruppe age group Zeitraum time period 0-24 -- 1959 total deaths TodesISlIe insgesamt Todesursache unbekannt Gewichtunosl aktor UflXilO WI weighting factor i960--1969 Todestalle insgesamt Todesursache unbekannt Gewichtungslaktor 1 0 5 0 1 25-34 7 0 1 35-44 6 2 1,5 45-54 12 2 1.2 55-84 65 + 13 2 1,1818 2 0 1 41 6 18 1 1.0588 27 2 1,08 39 4 1,1143 52 2 1.04 38 2 1,0556 179 11 1970--1974 TodeslSIle insgesamt Todesursache unbekannt Gewichiungsfaktor 4 1 1,3333 20 3 1.1765 32 3 1.1034 39 0 1 Tab. 1.1 VCM-exponicrte Arbeiler (Kohorte I) workers exposed to VCM 40 3 1.0B11 59 3 1.0536 (cohort 1) 194 13 Altersgruppe Zeitraum -- 1959 Todeslaile insgesamt Todesursache unbekannt Gewichiungsfaktor 0-24 3 -- 1 25-34 2 1. 2 35-44 45-54 55-64 65 + 13 5 1,625 17 5 1.4167 17 2 1,5455 3 3 14 Summe 55 18 1960--1969 Todeslaile insgesamt Todesursache unbekannt Gewichtungslaktor --3 13 21 35 96 44 212 1 1 7 8 3 20 1 1,0833 1,05 1,25 1,0909 1,0732 1970--1974 Todeslaile insgesamt Todesursache unbekannt Gewichtungslaktor 3 -- 1 Tab. 1.2 Nicht VCM-exponiene Arbeiter (Kohorte II) 6 11 21 37 72 150 --3 4 --2 9 1 1,375 1,2353 1 1.02B6 workers not exposed to VCM (cohort 2) Altersgruppe; Zeitraum -- 1959 Todeslaile insgesamt Todesursache unbekannt Gewichtungslaktor 0-24 1 -- 1 25-34 4 4 -- 35-44 4 2 2 45-54 55-64 65 + 11 3 1,375 11 3 1.375 4 2 2 Summe 35 14 1960--1969 Todeslaile insgesamt Todesursache unbe* innt Gewichtungslaktor 4 t 1.3333 17 2 1,1333 22 4 1,2222 29 S 1.2083 51 4 1,0851 56 5 1,098 179 21 - 1970-1974 Todeslaile insgesamt 3 7 18 21 Todesursache unbekannt 1 152 Gewichtungslaktor 1.5 t, 1667 1.3846 1.1053 Tab. 1.3 Arbeiler der PVC- Weiterverarbeilung (Kohorte III) PVC. processing 44 2 1.0476 Workers 53 146 1 12 1,0192 {, cohort J) SAL 000070607 -7- without exposure Kohorte t Kohorte It Kohorte III VCM-/PVC- Ohne VCM-/ PVC-Weiter- Herstellung PVC- CU':'C.*/fif. product .Exposition ing Populations^i-7/f//4, (Deutsche und Osierreicher) 7.021 4.910 4.007 Follow-up bis 31.12.1974 93.2 89.8 92.1% Ma nnj ahre'Vfctjf- 73.734 76.029 52.896 Bis 31. 12.1974 v'*e-r sVtorben ue-zr'Cz. Tooesursache nicht zu ermitteln cH :s*Tr- /::t05 A-- ysle-n dver ~ '\S davon verstorben 414 7.2 882 6 417 11,3 711 6 360 13.1 1.454 10 Tab. 2 Grundc/aien fur die Kohorter. I, II und III Basic data for cohorts 1,2,3 A comprehensive comparison of cohorts 1 and 2 (Table 3-5) shows in addition that the workers of cohort 2 earlier in time became a member of the investigated cohorts as a result of their entry into the company* 32-4 % of men years are found in the period to 1959 compared to l6-l % for the workers of cohort 1. The workers of cohort 2 were, moreover, slightly older than the workers of cohort Is calculated to men years, a percentage of 34.2 % in cohort 2 is found in age classes above 44 years compared to 28.2 % in cohort 1. agg grou P----------------------1 '^^Aitersgruppen time v. - 24 Zeitraum 25--34 35--44 45--54 55--64 65 + total Summe --1959 i960--1969 1970--1974 2142,11 4107,57 2016.32 4044,31 11841,72 7716.39 3007.49 9144.15 6933.28 1925,36 5479.80 4891.50 675.68 3287.0 2670.34 94.75 676,93 1079.15 ' 118e9,70 34537,17 . 27306,98 Summe total 8266.0 23602.42 21064.92 12296.66 6633,02 1850.83 73733,85 Tab. 4 Mannjahre von VCM-exponierten Arbeitern men years of workers exposed to (Kohorte I) VCM (cohortl) i-ersg ruppen ZeiUaum --1959 1960--1969 1970--1974 -- 24 3954,26 3465,97 1418,73 25--34 6850,10 9264,61 4270.88 35--44 7039,16 8265,61 5557,39 45--54 5285,66 5942.43 3862,21 55--64 1390,91 4248.09 2560.80 65 + 137,09 1074,0 1441.02 Summe 24657.40 32260,71 19111,03 Summe 8838,98 20385,59 20862,16 15090.50 0199.80 fab. 5 Mannjahre von nicht VCM-exponierion Arbeitern men years Of 2652.11 76029,14 g6 ^ cojlor^2/Ko/70rte ^ 000070608 SAL- Table 3. Year o f b ir th and f i r s t exposure resp e n try in to the company. -8- exposed to VCM resp. PVC KOHORTE I l- Exposition gegen VCM brw. PVC in 19.. ryTsar-T-wi DlT -- Geburtsjahr --44 45-49 50-54 55-59 60-64 65-69 70-74 -1884 2 1 --_ __ _ 1885--1889 1 4 1 -- -- -- .-- 1890--1894 3 5 5 1 ---- -- 1695--1899 6 22 16 8 7-- -- 1900--1904 11 23 35 38 20 4-- 1905--1909 9 24 63 64 54 29 1 1910--1914 16 26 78 88 77 42 13 1915--1919 4 22 95 91 52 42 24 1920--1924 8 41 122 135 97 61 70 1925--1929 5 25 147 198 142 154 130 1930--1934 -- 17 107 264 230 252 177 1935--1939 -- -- ' 42 272 360 269 262 1940--1944 ---- 6 132 297 363 302 1945--1949 ---- -- 1 94 245 294 1950--1954 -- -- -- .-- 1 64 368 1955--1959. ---- ---- -- -- 78 ----------------- ------------------------------------ sntry^lnto KOHORTE !l Einiritt in den Betrieb in 19.. company Geburtsjahr --44 45-49 50-54 5-59 60-64 65-69 70-74 -- 1884 1885--1689 1890--1894 1895--1899 1900--1904 1905--1909 1910--1914 1915--1919 1920--1924 1925--1929 1930--1934 1935--1939 1940--1944 1945--1949 1950--1954 1955--1959 -- 2 -- -- -- __ _ 7 2 -- i-- -- -- -- 14 13 2-- ---- -- 65 19 3 1 -- -- -- 124 61 19 16 1---- 112 66 45 44 7 2 -- 112 77 71 91 21 2 1 30 58 76 62 28 9 2 50 89 118 127 59 31 16 53 69 125 156 70 51 33 5 45 127 222 126 67 51 -- -- 64 245 193 136 81 ---- 4 147 157 141 94 ------ 5 66 142 113 -- ---- 3 78 167 ---- ---- -- 5 72 exposed KOHORTE 111 1. Exposition gegen PVC in 19.. PVC Geburtsjahr --44 45-49 50-54 55-55 60-64 65-69 70-74 --1884 1885--1889 1690--1894 1895--1699 1900--1904 1905--1909 1910--1914 1915--1919 1920--1924 1925--1929 1930--1934 1935--1939 1940--1944 1945--1949 1950--1954 195S--1959 1 1 ---- ---- _ 2 11 1 -- ------ 3 IS 13 2 -- --. -- -- 17 2B A 9---- 2 47 42 16 23 1-- 3 30 39 55 48 3-- 3 36 51 111 62 n 11 6 30 34 92 54 17 23 10 47 47 148 72 23 19 7 25 75 215 105 41 26 -- 16 75 254 168 66 * 40 -- -- 36 289 253 90 49 -- -- 2 54 222 124 77 -- -- -- 41 25 99 77 -- -- ---- 1 17 135 -- -- -- -- -- -- 16 SAL 000070609 9- - These differences in structure must be properly considered in comparing the SMR. The follow-up for all three cohorts shows values leading to the supposition that the SMR would not relevantly change as a result of a more comprehensive explanation of the fate of workers whose addresses could no longer be determined. The percentage of no longer explainable causes-of death is only desirably low in cohort 1. In view of the 5 year record keeping term for death certificates we will have to accept values of about 10 -fo for unexplainable causes of death in the Federal Republic also for future investigations. 3.2 Standardized mortality rates A. Total mortality The total mortality of cohorts 1 and 3 with 95 each is found very close to the total mortality of the total population (Table 6). Cohort 2, on the other hand, with an SMR of 78 has a clearly lower value compared to the total population. When considering the total mortality in the individual age classes (Table 9, 11, 15) a lowep SMR is found in cohort 1 only for the workers under 25 years of age and for the 55-64 year old workers? only the latter is statistically significantly reduced. Cohort 3 in all age classes has a total mortality which equals the total population. 'The SMR of cohort 2 for the 25-54 year old workers, on the other hand, is significantly lower. When analyzing the SMR for the total mortality of the three cohorts according to the observation period, the lowest value is obtained for all in the period up to 1959* This lower value is, how ever, only statistically significant for cohort 2 and cohort 3, Cohort 2, in addition, shows a lower SMR in the period from 1970 to 1974 (Table 7, 10, 13). J B. Specific SMR In the following, only those specific causes of death with their SMR will be discussed which were found beyond the 95 # con fidence range with the SMR definition under the assumption of a Poisson's distribution. As mentioned above, instigation for the study was the observation of individual cases of hemangiosarcomas of the liver in workers exposed to VCK. The ICD code 155 includes all malignant tumors having their primary seat in the liver. As a result of the extreme rarity of this disease and its relative unfamiliarity in earlier years, the exact diagnosis of hemangiosarcoma in long ago deaths 000070610 SAL- -10- could be seldom made and as seldom be filled in on the death certificate. In this respect, statements on a higher SMR can only be made by also including other malignant liver tumors. In the cohort of the workers exposed to VCM, the SMR for malignant tumors of the liver with 1523 is extremely high (Table 6). This elevation is found in all age classes of the cohort in which malignoma of this type were observed. The highest values occur in the age classes 35-44 year old workers (Table 9) .. A very clear SMR elevation is found over the individual observation periods (Table 7) and an equally clear increase with increasing exposure duration to VCM (Table 8). A comparatively lower SMR elevation for liver malignoma is found in cohort 2 (SMR = 401). A more detailed classification of the few observed cases only indicates an increase between i960 and 1969 (Table 10). The STAR elevation for malignant tumors of the digestive organs (ICD 150-159) in cohort 1 could possibly be traced to the liver malignancies occurring in excess in this cohort (Table 6). When subtracting the number of liver malignoma from the total malignoma of this range, an SMR is obtained which is not any longer statisti cally significantly increased with 109. Only in a classification according to observation period and only for the time to 1959* an increased SMR for malignoma of the stomach (ICD 15l) with 446 is found (Table 7). In cohort 1, the SMR for tumors of the lymphatic and hamatopoeti-c tissue (ICD 200-209) with 2l4 is clearly higher. It is suggested that an increase occurs with increased exposure time (Table 8), although none of the values is statistically significantly higher because of the small number of observations in this type of classification. A classification according to observation period seems to indicate an increased frequency between i960 and 1969 (Table 7) - A higher SMR is found in cohort 3 with one form of malignoma* malignant brain tumors compared to the total population are higher by 435 # (Table 6). A preference in the 45-54 year old worker (Table 15)and an increased frequency beteen i960 and 1969 are found (Table 13)* All three cohorts have an SMR increase in common for ischemic heart diseases (ICD 4l0-4l4) (Table 6). A sub-division according to observation period results in a non-uniform situation* in cohort l an increase is only found between i960 and 1969* in cohort 3 as of i960 and in the cohort of workers not exposed to VCM only since 1970 (Tables 7* 10, 13)- A sub-classification according to age classes indicates a preference in higher age classes (Table 11, 15)- 00 ?0*1] -11- Only in the cohort of workers exposed to VCM, an increase in accidents of all types (IGD 800-949) is recorded. In this case, an increasing tendency is demonstrated with observation period (Table 7) 4. Discussion The results of different published mortality studies show such a varied situation that it is difficult to recognize a common pattern, (3, 4, 6, 7, ll). Whereas Duck et al (1975) USA for a population of persons indicate a total mortality of 96 with lower SMH at increasing exposure duration (under ten years of exposure* 112, ten to fourteen years of exposure* 107* fifteen and more years of exposure* 6l) Duck and Carter (1976) correct the result for the worker group with the longest exposure to an SMR of 104. In contrast, Fox and Collier (1977) find a total mortality of 75-^ for a population three times as large and a considerable fluctuation between the various investigated Brittish plants (SMR 12.3 to 88.8). Their analysis shows also a continuously lower SMR tendency since the first observation period* whereas it was still 87,4 for 1940-1944, it dropped to 53-1 for the period of 1970-1974. In a classification according _to exposure duration, these authors, however, find a clear increase* men, still alive 15 years after the study began, show an SMR (100.6) for an exposure duration of up to five years which does not differ from the total population; it already reaches a value of 113-3 for an exposure duration of ten to fourteen years. The two US studies (4, 12), to be sure, have the largest study population available (N = 9*677) and the largest number of person years (120,203 in (4)) tut their results are sometimes contradictory* whereas the first analysis (Tabershaw and Gaffey, 197^) in a follow up of 85 % still has an SMR of 75* the second analysis with an improved follow-up of 95 $ shows an SMR of 89 (4). With increasing exposure duration, to be sure, a slight but inconsistent SMR increase is found in the second analysis. The SMR in the group of men exposed for the shortest time (1-4 years) and with the least ex posure intensity indicating a `'healthy worker effect" is neverthe less equally significantly reduced (SMR 82) as the SMR of the highly exposed men (5--9 years, SMR 48) resp. the SMR of a group of men 'with average exposure intensity who were exposed for a long time * (20-24 years) (SMR 66). These inconsistent tendencies do not allow a meaningful interpretation at this time. A comparable "healthy worker effect" is, in contrast, not found in the workers of BASF, Ludwigshafen studied by Frentzel-Beyme et al (1978). A lower SMR (70) was only found for the group ex posed for the shortest time (up to 4 years) whose exposure started after i960 whereas all other groups had higher values. This study SAL 000070612 -12- group could also observe an effect similar to the effect observed by Fox and Collier (I978)i an earlier exposure start results in a higher SMR (before I960, SMR = l4o* after i960, SMR 102). Also in this population, moreover, the longer the minimum observation time of the population, the higher the SMR, the SMR for a minimum observation time of 5 years is 99, for a minimum observation time of 10 years, on the other hand, it is 1174. When in a population consisting of industrial workers who must provide a selection with respect to health, a difference in the total mortality compared to the total population is not found, it must be assumed that the SMR is relatively elevated. This assumption is confirmed by the comparison of the SMR's of the three investigated cohorts (Table 6). Accordingly, only cohort 2 (not exposed to VCM) shows, the "healthy worker effect* It is lacking in cohorts 1 and 3. The considerable differences with respect to total mortality and also to specific mortality found in comparing the US study and the study by Fox and Collier with the present study must be discussed under the topics of different detecting methods in determining the population of exposed workers and of different exposure intensity. Whereas Fox and Collier included all workers who "could" have been exposed to VCM in the population of their study, the population of the German study was limited to those workers who were clearly and continuously exposed. This results in a comparatively more intensely exposed German population. Further references to a comparatively lower exposure result from a comparison of the PVC production numbers for 1974t Great Britain West Germany Table 12. workers 7*717 7,021 product ion in tons 381,000 1,070,000 consumption in tons 410.000 943.000 capacity in tons 575,000 1,355,000 When assuming an approximately equal productivity in the PVC chemical industry per worker, the British population as a result of fewer or hardly exposed workers would have to be "diluted" to a reduced risk. It does not seem probable, however, that the British productivity is only one third of the German productivity (Great Britain* 49,400 tons per 1000 workers* Germany 152,400 tons per 1000 workers) When assuming, on the other hand, a reduced productivity and a comparable PVC production technology, a resulting VC burden on the population would be divided over a comparatively larger population resulting again in a lower exposure per population unit. These effects unfortunately cannot be estimated since Fox and Collier only give total numbers of their population but not person years. 0000 The most important finding of the present study undoubtedly concerns the much higher SMR for malignoma of the liver. Fox and Collier find a significantly higher SMR only in the most burdened sub-group of their population. The American studies, on the other hand, do not mention an increased mortality risk for malignoma of the liver although, meanwhile, 85 hemangiosarcomas of the liver in personsexposed to PVC became known by the end of 1980 with the largest number in the USA. These differences can be traced to various factors: 1. Since there is no indication that more intensively or longer exposed persons in Great Britain were investigated less exactly than in the Federal Republic, a more intense total exposure in the Federal Republic could be concluded. 2. The lacking increase in the USA again could have three reasons: The fixed date of detecting the population in the US was December 31 1972. It can be assumed that with the relatively long latency period a number of persons were not included until later years. It is also possible that the SMR for primary liver tumors (ICD 155)has increased but ife not expressed in the results. In the SMR tables, all causes of death traced to diseases of the gastrointestinal tract and the peritoneum (ICD-7 150-159) are combined. - It can be suspected that the ten cases observed in this study falling under the category ICD 155 would lead to a significantly higher SMR also in the American study with a separate cal culation of the SMR for the ICD position 155* The SMR increase observed in the present study for tumors of the lymphatic and hamatopoetic system (ICD 200-209) is not found in any other study in this manner. The American study, however, includes a suggested increase for leukemia/aleukemia (ICD. 204) as well as for lymphoma (ICD 200-203, 205)- The SMR increase observed in our study for ischemic heart dis eases (ICD 4l0-4l4) (see Table 6) would under the circumstances have been incorrectly attributed to exposure to YC if a comparable increase would not have been found also in the cohort of the unexposed workers and in the cohort of workers of PVC processing. This demonstrates the great advantage of the analysis of a comparison group consisting of industry workers. The result of the ischemic heart diseases at the same time pointed out an imminent methodical defect of this study formulation: the essential risk factors for ischemic heart, diseases but also for various carcinoma (smoking. Sal 00070614 -14- dietary habits, etc.) cannot be detected and escape the analysis, therefore. The present findings impressively support the deter mination already made in 1977 by the National Institute for Occupational Safety and Health (NIOSH) (Key et al, 1977) that vinyl chloride must be viewed as carcinogenic for humans and is causally responsible for angiosarcomas of the liver. It must be expected that as a result of the long latency period assumed for the development of hemangiosarcomas of the liver but also for other tumors, a further collective follow-up investigation of exposed workers will provide definite state ments on the carcinogenicity of VCM, 5. Summary 1. In a historic prospective mortality study the fate of all of the male employees of the chemical industry in West Germany engaged in the production of vinyl chloride monomer and polyvinyl chloride as well (1-1 factories) is studied. Employees of German and Austrian nationality only have been included in the analysis (N 702l). For various reasons, the data of 882 foreigners (6 of whom deceased) were excluded. 2. The fate of 4,007 employees of the PVC processing industry (2 factories) and of 4,910 employees of the chemical industry without exposure to VCM/^VC has been analyzed in identical manner. 3. Follow-up rate came to about 90 % at the endpoint of the study (12-31-1974). Resulting person years came to 73734 (VCM/PVC exposed), 52,896 (PVC processing), and 76,029 (without exposure to VCM/PVC) respectively. 4. Using the male population of West Germany within the respective calendar years as reference, the standardized mortality rate (SMR) of employees exposed to VCM/PVC or engaged in PVC processing failed to demonstrate any "healthy worker effect", 5. SMR for malignant tumors of the liver (ICD-8 155) shows an extraordinary dose-dependent elevation for VCM/PVC workers. A relatively small increase for ICD-8 155 is also to be found in nonexposed workers. 6. SMR for malignancies of lymphatic and hematopoetic tissues (ICD-8 200-209) is considerably increased in VCM/PVC exposed workers. 7. SMR for malignancies of the brain (ICD-8 191) is elevated in employees of PVC processing factories. 8. All of the three cohorts analyzed demonstrate an elevated SMR for ischemic heart diseases (ICD-8 4l0-4l4) 0 -159* Considering the long latency periods for malignant tumors and the increasing number of observations of hemangiosarcomas of the liver (West Germany 197^* 4 cases, 1980* 18 cases) as well, further follow-up studies of the population exposed to VCM/PYC seems to be highly advisable. SAL 000070616 -16- 50______ Yinylchloriii'Eiflositifitt u. SfnrtaliidiZbl, Arfacitsmed. 32 (I9S2) 3 Table 6. SMR of cohorts 1, 2, 3 of the study exposed to not exposei PVC process Kohorte 1 Kchorte II Kohorle HI - VCM-/PVC- Keine VCM- PVC-Weiter- Exposition Exposition verarbeilung ICO Diagnose ooservation va. -S&b, expection valu wert * Erw.- wert SMR Beob.wert Erw.wert SMR Beob.wen Erw.. wen SMR 140-209 140-199 200-209 150-159 151 153 155 160-163 162 186 191 410-414 410 430-438 490-493 571 800-949 950-959 Oil Gesamtmortalitat total mortality 414 434,7. malignant tumors ana system- MaligneTumoren der Organe atlC lsi^ihe-^Srse g^1enoma Maligne Tumoren der Organe "the organs tumors of the lymphatic and Tumoren des lymphatischen hematop. und haemalopoetischen Gewebes tlSSUe of. the digestive organs Maligne Tumorerroer VerdauungstSrgane of the stomach Maligne Tumoren des Magens of the colon MaligneTumoren des Dickdarms of the liver Maligne Tumoren der Leber of the respiratory system Maligne Tumoren des respiratorischen Systems of the trachea, bronchia Maligne Tumoren der Trachea,-] 17 nr<3 94 90.6 79 82,9 15 7.7 45 32,7 18 14.4 6 5.8 12 0.9 24 26,6 22 24.6 Maligne Tumoren der Harnbtase of the brain Maliqne Tumoren des Gehirns ischemic heart disease 1 2.9 2 1.3 Ischaemische Herzkrankheiten acute heart muscle infarct Akuter Herzmuskelinfarkt cerebrovascular diseases- . Cerebrovaskulare Krankheiten --------- bronchitis emphysema asthma Bronchitis. Emphysem und Asthma cirrhosis of the liver Leberzirrhose accidents . Unfatle suicide, self destruction Suizid und Selbstbeschadigung lung tuberculosis Lungentuberkulose 91 76,5 66 61,8 29 29.4 6 14.4 14 18.4 61. 49 24 25.5 4 5.5 95 417 533 112 103 214'* 149* 138 109 1523** 96 95 36 162 127* 114 104 44 82 137* 101 75 83 113.7 77 104,8 6 8.9 27 41.8 10 Itt.b 3 7.3 4 1.1 30 34 30 31,5 2 3.7 2 1,6 115 96,7 83 77.1 25 ' 39.2 10 19.2 17 21,3 44 51,3 16 27.3 4 6.9 360 379,6 95 i S3 83 77 71 62 42 401* 100 108 63 183 13V* 120 70 59 92 99 70 65 62 81.9 60 /o.b 2 6.3 15 30.3 7 13,5 1 5.3 3 0.8 25 24.4 24 22.6 2 2.B 5 1,1 96 69.4 69 55 23 29.7 4 14,2 14 15.4 32 35.5 15 19 0 4,8 85 89 34 56 57 26 434 113 116 77 535** 158** 143'1 82 30 105 110 92 *) Oberschreitung des95%-vertrauensbereichs exceeding the 95 % confidence range ') uberschrenung des 99%-venrauensbereichs exceeding the 99 Y* confidence range (J. C, BAILAR: Significance Factors for the Ratio of a Poisson Variable to its Expectation. Biometrics 20; 639-643. 1964) Tab. 6: SMR der Kohorien I, II und III der Studie SAL. 000070617 -17- Zbt. Arbriiymed. 32 C19S2) 2Vinylchloritf-Kxpcsilion u. MortoUtdt_______________________________ j] Table ? SMR acc. observation period for VCM exposed workers (cohort l) _________ observation periodBeobachtungszeilraum -- 1959 1960 -69 1970 -74 observ. value Beob.- Beob.- Beob,- ICD Diagnose expect, value Erw.- SMR Erw.- SMR Erw.- SMR wert wort wen 140-209 140-199 200-209 150-159 151 153 155 160-163 162 188 191 410-414 410 430-438 490-493 571 800-949 950-959 011 Gesamtmortatitat total mortality 41 52,5 of the organs and syst. malig n Maligne Tumoren der Organe 13 und svstematische Malignome of the organs Maligne Tumoren der Organe 9.8 12 of the lymph, and hematopoet. Tumoren des lymphatisehen ec3no 8,8 1 oTd ttfi*miS!^&we<S!fgans 1 Maligne Tumoren der Verdauungsorgane 8 of the stomach 3,5 Maligne Tumoren des Magens 6 of the colon Maligne Tumoren des Dickdarms of the liver Maligne Tumoren der Leber of the respiratory system Maligne Tumoren des respiratorischen Systems of the trachea, bronchia Maligne Tumoren der Trachea. lungs ofr!t!Ken tSfa&cPir Maligne Tumoren der Harnblase of the brain Maligne Tumoren des Gehirns ischemic heart disease Ischaemische Herzkrankheilen acute heart muscle infarct Akuter Herzmuskelintarkt cerebrovascular Cerebrovaskulare Krankheiten ------- 1 0.6 1 0,09 1 2.7 1 2.4 0 0,3 1 0.2 7 7.9 7 6.5 1 2,7 Bronchitis. Emphysem und Asthma cirrhosis of the liver Leberzirrhose 1 1.4 1 accidents Unfalle suicide and selfdestruction Suizid und Selbstbeschadigung suberculosis Lungentuberkulose 7 7.9 0 4 2 0.8 78 159 160 147 270* 446** 196 1282 -- 44 48 557 103 125 44 86 62 103 245 179 194.7 38 40,5 29 37 9 3.5 13 14.9 3 1 2.5 3 0.4 14 11.8 12 10.9 1 1.2 0 0.7 43 33.2 32 26.8 13 13.1 1 6.7 7 27 22,9 9' 12 2 3 92 194 187.5 103 101 84 275** 94 48 43 824* 127 117 88 _ 138* 128 104 15 101 125 79 70 43 40,3 38 37,2 5 3.1 24 14.4 9 113 .. 108 168 177* 158 4 2,6 8 0.4 9 12.2 9 11,3 0 1.4 0,4 41 35.4 27 28,6 15' 13.6 4 6.3 6 153 2264** 78 84 223 122 100 116 65 71 27 18.3 15 9.6 0 1.7 167* 170 ') Uberschreityng des 95H-Vertrauensbereichs &S in Table *") Uberschreilung des 99*A-Vertrauensbereich$ (J. C. BAILAR: Significance Factors lor the Ratio of a Poisson Variable to its Expectation. Biometrics 20: 639-643. 1964) 6 Tab. 7: SMR nach Beobachtungazeitraum bei VCM-exponierten Arboitam (Kohorle I) SAL 000070618 18 52_____ Ta57 U i'lnvIrhlnrid-Exposition u. Mortaliiat SMR acc. exposure duration for VCM exposed workers (cohort l) Zbl. Arbcitsmcd. 32 (19S2) 2 exposure duration (months) Expositionsdauer (Monale) -- 12 13-60 observ. v ,Bcob.- wert ICO Diagnose expect* V ,Erw.- wert 140-209 140-199 200-209 150-1S9 151 153 155 160-163 162 188 191 410-414 410 430-438 490-493 571 800-949 950-959 on total mortality Gesamtmortal/lat sysWt.ldmoargliganns. ana Maligne Tumoren dec Organa uod systematische Malignome ox the organs Maligne Tumoren der Organe of the lymph, hem. Tumoren des lympnaiischen und Maligne Tumoren der ormnsifffiS'ach Maligne Tumoren des Magens Maligrfoerumo^n3es DicKdarms, . of the liver Maligne Tumoren der Leber of the resp. syst. Maligne Tumoren des respiraiorischen Systems Maligne Tumoren der Trachea. Bronchten und Lunge 3f the bladder Mangne Tumoren der pf^STbrain Maligne Tumoren des Qehirns ischemic heart dis. tschaemische Her2krankheiien leart mus. infarct Akuter HerrmuskeiinTarkT Cerebrovaskulare Krankheiten Bronchitis. Emphysem und Asthma * liver accidents Unlalte suicide and selfde Suizid und Seibstbeschadigung Lungeniuberkulose 53 57.3 59 66.5 6 9.2 1 1.1 3 3.5 2 1.5 1 0.6 0 0.09 1 2.8 1 2.5 0 0,3 0 0.2 9 8.2 6 6.8 0 2.9 0 1.4 1 2,3 11 10.3 5 4.7 0 0.7 SMR Beob.wert Erw,- wert 93 138 135.9 90 158 159.8 74 20 23.9 72 4 2.5 101 12 9.4 168 7 4.1 154 1 1J 2 0.2 38 6 7.3 41 6 6.6 'o 0.8 O ' 0.4 117 25 21.6 95 " 19 17.5 10 8,6 0 4.1 46 2 5.5 117 27 19,2 114 12 9.5 `2 1,7 SMR 102 100 88 186 135 175 71 874* 85 93 123 115 123 40 158* 135 119 61 - 120 121 + Beob.wert Erw.wert SMR Beob.wert Erw.- wert SMR 93 106,7 87 130 134.7 96 125 127.6 22 20.9 5 1.9 13 8.3. 7 3.7- 3 1.5 3 0,2 6 6.8 6 6.2 1 0.7 1 0.3 19 19.4 14 15.6 7 7.5 3 3.7 8 4.6 12 10.7 4 5.9 1 1.4 92 116 267 173 215 215 1525'* 95 103 144 350 106 98 99 89 140 121 73 71 161 163.6 31 28.9 52*1 17 11.5 2 5 1 2 7 0.3 n 9.8 9 8.1 0 101 t 0.4 38 27.2 27 21.9 12 10.5 3 5.2 5 6 11 8.9 3 5.4 1 . 1.6 99 115 249 158 41 50 2528** 121 106 278 148* 131 122 58 90 135 60 63 ') Oberschreitung des 95e<*-Veruauensbereichs **) Oberschreitung des 99W-Vertrauensbereichs (J. C. BAILAR: Significance Factors lor the Ratio o? a Poisson Variable to its Expectation. Biometrics 20: 639-643. 1964) SAL 00007061? 19 S4 Tab, 9* WnytchlarM'-Expflsition u. Manolitdi SMR acc. to age classes Zhl. Arbcitsmefi. 32 (I9S2) 2 Alier$kisuen ClaSSeS -- 24 25-- 34 35 -- 44 45- 54 55- 64 65 + obs. va; .^pob- Beob- Beob- Baob- Beob- Beob- i expect. achiWigs- wen SMR eehtungs- weri SMR eehtungswen SMR aeh* tungs- wan SMR achlungswen SMR. achlungswen SMR ICO Diagnose Erwartungs- wert Erwarlungswen Erwerlungswen Erwarlungs- wert Erwar- lungswert Erwarlungs wen total mortality Gesamtmortalital 10 14,6 66 45 111 65 104 90 40.5 62.5 89 101 105 60 90 103 131,9 96.2 1*0- 209 140- 199 200 - 209 150- 159 151 153 155 160- 163 162 168 191 410-414 410 430- 436 490- 493 571 800 * 949 9SO - 959 011 Maligna Tumoren Cer Organs und systematise!-!* Mahgnom* Maligna Tumoren Tumoren Oes tympntiiacften und haematopoetischen Gewebes Maligna Tumoren der Verdauungsorgane und oes Peritoneums Maligne Tumoren des Magana Maligne Tumoren des Dickderms Maligns Tumoren der Leber Maligne Tumoren des respiratoriscfien Systems Maligne Tumoren der Trachea. Bronchien und Lunge Maligne Tumoren der Harnblase Maligne Tumoren des Gehirns tschaemisehe Herzkrankheilen Akuter Herzmuskelintarkt Cerebrovascular* Krankheiten Bronchitis. Emphysem und Astnma Leberurrtios* Untalle Suizid und Selbstbeschidigung Lungeniuberkutose 0~ 0 00.6 00.4 00,08 0-- 0,003 00.03 0-- 0.002 0 0.05 - 00.05 0 0.CO4 - 0-- 0.03 00.07 0 0,07 - 00.1 0-- 0.05 0-- 0.05 7 100 7.6 1 49 2 0 -- 0,02 o fot 6 4.0 4 2.9 2 1.1 3 0,8 2 0.3 0 0.2 D 0,02 0 0.3 0 0,02 0 0.2 2 1.2 2 U 0 0.7 0 0,2 0 0.9 22 14.4 4 6.5 1 0,4 156 141 194 397 740 - 191 210 - 17V . 69 266 17 9.4 13 7.6 4 1.6 10 3.1 2 1.3 1 0.7 6 0.096 1 1.7 1 1,5 0 0.3 0 0.4 7 7.7 5 6.9 1 1.6 0 0.7 2 3.6 11 11.7 9 7.3 0' 1.1 208 168' 303 365" 206 163 6665" 64 73 98 76 60 61 106 13S -- 23 19.6 19 16 4 1.6 10 7.4 5 3.3 4 1.2 0 0.2 6 5.7 4. 5.2 0 0,5 0.4 26 16.6 20 16 3 4,1 2 2 4 6.2 13 7.6 4 5.4 0 1.5 126 114 264 145 165 337 113 81 254 150 134 75 100 65 187' 77 - 24 33.5 22 31.5 3 2 ID 12.4 5 5.5 0 2 3 0.4 10 11.6 10 10.8 0 1.1 1 0.3 33 29.3 27 23,6 12 10 2 5.7 3 5.9 3 5.5 4 3.4 1 1.7 81 23 23.3 76 21 22.2 162 2 1,1 69 12 9 101 4 4.1 -1 1.6 934" 3 0.2 92 7 7,4 99 7 6.6 -1 1 362 0 0.06 121 22 19.6 122 12 14 127 13 12.7 39 2 5.7 55 5 2.7 56 5 2.2 124 2 0.9 62 0.8 0.6 105 100 197 140 104 65 1664 100 108 104 122 90 108 37 194 240 225 262 `Uberschreitung des 95tt-Vertraueftsbereichs "Oberschreitung des 99%-Vertrauensbereich {J. C- Bailar: Significance Factors for the Ratio of a Poisson Variable to its Expectation. Biometrics 20:639-643.1964) SAL 000070620 20 Zbl, Arfaeinnaed. 33 (3982) 2 WnylcMorid-Exposition u. MonalitSi Tab. 10. SMR for unexposed to VCM-workers Observation peri0d observation period Beobachtungszeitraum ICO Diagnose Gesamtmortalitat -- 1959 Beob.wert Erw.wert SMR 55 115,3 48** 1960 69 Beob.wert Erw.- wert SMR 212 232.4 91 1970 -74 Beob.wert Erw.' werl SMR 150 185.4 87" Total Seob.wert Erw- wert SMR 417 533.0 78" 140-209 140-199 200-209 150-159 151 153 155 160-163 162 188 191 , 410-414. 410 430-438 490-493 571 800-949 950-959 Oil Maligne Tumoren der Organe und systematische Malignome Maligne Tumoren 7 21.7 7 19.1 Tumorendeslymphatischenund haematopoetischen Gewebes 0 2.2 Maligne Tumoren der Verdauungsorgane 1 7.7 Maligne Tumoren des Magens 1 3.5 Maligne Tumoren des Dickdarms 0 1,3 Maligne Tumoren der Leber 0 0.2 Maligne Tumoren des respiratorischen Systems 3 5.8 Maligne Tumoren der Trachea. Bronchien und Lunge Maligne Tumoren der Harnblase 3 5,3 0 0.5 Maligne Tumoren des Gehirns 2 0.5 Ischaemische Herzkrankheiten 6 17,7 Akuter Herzmuskelinfarkt 6 14.7 Cerebrovtskulare Krankheiten . 2 5.5 Bronchitis, Emphysem und Asthma 1 2.8 Leberzirrhose 2 4,4 UnfSlIe 9 16.0 Suizid und Selbstbeschadigung 3 8,5 Lungentuberkulose 0 1,9 48 54 -- 20 44 -- -- 77 84 -- 597 51 61 _ 56 52 % 70 79 54 . -- 49 50,8 45 46.9 4 3.9 16 19 6 8.7 1 3.2 3 0.5 18 15.4 18 14.2 2 1,6 0 . 0,7 50 42.1 40 33.4 12 17.6 5 9,1 11 8,9 24 21.8 8 11,8 4 3.5 108 107 ns 93 77 34 680* 130 140 144 -- 132 184 73 61 135 118 76 128 27 41.6 25 38,8 2 2.8 10 15,2 3 6.4 2 2.8 1 0,4 9 12.9 e 12 0 1.6 0 0.4 59 36.9 37 29 11 16.1 4 7.3 4 8 11 13.5 5 7.1 0 1.6 68 67 65 69 51 73 266 74 80 -- -- 167" 135' 70 59 56 92 78 -- 83 113.7 77 104.8 6 8.9 27 41.8 10 18.6 3 7.3 4 1.1 30 34 30 31,5 2 3.7 2 1,6 115 96.7 83 77.1 25 39,2 10 19.2 17 21,3 44 51,3 16 27.3 4 6.9 83 83 77 ;i 62 42 401" 100 108 63 184 131" 120 70 59 ? 92 99 70 65 ') Oberschrcilung ties 95%-Verlrauensbereichs ") Llberschreitung des 99%-Vertrauensbereichs (J. C. BA1LAR: Significance Factors lor the Ratio of a Poisson Variable to its Expectation. Biometrics 20. 639-643, 1964) HI OOOO/'fl/o ''&31 21 56______ Ta5^ 1U ICO Vinylchforiil-Exposition u. Mnna/iini SMR ace.- to age classes for workers not exposed to VCM (cohort 2) AimrjkiAjscn Zb). Arhciumcd. 32 (I9S2) 2 age classes Oiagnose observ. -- 24 val. Saod- ach* tungs* w*n SMR 25-- 34 Beobachlungs* wen SMR 35-- 44 Beobach* lungsw*rt SMR 45- 54 Beobachtungswen SMR 55-*64 Beobachtungswan SMR 65 + Seob* achtungs* wen SMR expect, val. Erwartungswan Erwartungs* wen Erwartungswen Erwarlungswen Erwartungs- wart Erwar* tungs wen total mortality Gesamimorulitat 9 16,2 56 21 36.6 57 46 63.9 72 72 65 149 91 120 85 111.0 163.5 141.7 140- 209 140 - 1&9 200- 209 ISO* 159 151 153 155 160- 163 162 166 191 410 - <14 410 430- 436 490 493 571 600 949 950 - 959 Oil Maiigne Tumoren der Organt und systematises Malignome Maligna Tumoren Tumoren Oes lymphatiscnen und haenalopoetisehn Gewebes Maligna Tumoren der Verdauungsorgana und des Periioneums Malign* Tumoren des Magenj Maligna Tumoren des Dickdarms Maligna Tumoren der Leber Maiigne Tumoren des respiratoriscnen Systems Malign* Tumoren der Trachea, Bronchien und Lunge Maiigne Tumoren oer Harnblase Maiigne Tumoren des Gehirns ischaemische Herzkrankheiten Akuter Herzmuskelinlarkt Cerebrovueulire Krankheiten Bronchitis. Emphysem und Asthma Labarzirrhose Untaila Suizid ur>d Setbstbeschadigung Lungentuberkutoae 0_ 1.0 0 0.6 0 0.4 0 0.09 _ 0 0.03 0 0.04 0 0.002 0 0.06 0 0.05 0 0.004 0 0,04 r, _ 0 0.07 0 0.07 0 0.1 0 0.6 _ 0 0.06 9 111 6.1 0 2.2 0 0,02 3 89 3,4 3 121 2.5 0 0.9 1 149 0.7 0- 0.2 1 524 '0.2 0 0.02 0 0,2 0_ 0.2 0 0.02 0 0.2 0 1,0 o'" 0.9 __ _ 0 0.6 o' . 0.2 0 0.7 12 105 12.4 3 53 5.6 0 wm 0.3 6 9.5 3 7,9 2 1.6 3 3.2 2 1.3 0 0.7 1 0,1 0 1.7 0 1.5 0 0.2 0 0.4 8 8 7 7.1 1 1.9 0 0.7 1 3.3 7 11.4 4 7.2 0 1.2 61 IB 97 24,3 42 17 100 22J 155 105 172 1059 _ 117 116 64 34 87 61 2 3 40 9.2 2 59 4.2 0 1.5 o-- 0.2 6 112 7.0 6 121 6.5 1 222 0.5 2 S75 0.5 14 22.8 78 13 19.5 85 0 5.2 3 155 Z5 J> 40 62 6 82 9.4 74 96 6.7 1 62 2 33 87 24 74 41.5 34.1 32 90 22 71 39.1 32.5 45 2,4 134 1.6 10 15.4 73 10 13,3 79 4 69 6.9 2 6 35 0 . 2 88 2,5 2.4 249 0.4 753 0,3 14.3 16 13,3 0 1.4 0 0.4 42 36.1 33 29.2 8 .125 5 7.1 71 7.2 7 6.8 124 133 125 122 72 74 179 119 101 4.2 1 50 2.2 10.7 78 B B4 9.9 1 72 1.5 0 0,09 51 28,7 168" 30 20,3 159` 16 68 19 25 8.5 81 3.9 3 98 3.2 , 1.3 2 183 1.2 `UberscnreiJufig des 95Ve-V*rtrauensbefeich$ '`Oberschreiiung des 99%-Verirauensbereich (J. C. Bailar: Significance Factors for the Ratio of a Poisson Variable to its Expectation. Biometrics 20:639*643, 19547 SAL 000070622 3S__ Tab 13 -22 I/i/jrlchJoriti-Exposition u. Monoliigi SMR acc. observation period for workers from PVC processing (cohort 3) Zbl. ArbciKmed. 3} (19S>) 2 observation period BeobachUingszpilraum (CD Diagnose Gesamtmortaliiat -- 1959 observ. v. expect. V. Beob.wert Erw.wen SMR 1960 -69 Beob.wen Erw.wert SMR 1970 -74 Beob.wert Erw.wert SMR 35 57.4 6V 179 100 99 146 142.2 103 140-209 140-199 200-209 ISO-159 151 153 155 160-163 162 168 191 410-414 410 430-438 490-493 571 800-949 950-959 011 Maiigne Tumoren der Organe und sysiematische Malignome Maiigne Tumoren der Organe Tumoren des fymphatischen und haematopoetischen Gewebes Maiigne Tumoren der Verdauungsorgane Maiigne Tumoren des Magens Maiigne Tumoren des Dickdarms Maiigne Tumoren der Leber Maiigne Tumoren des respiratorischen Systems Maiigne Tumoren der Trachea, Bronchien und Lunge Maiigne Tumoren der Harnblase Maiigne Tumoren des Gehirns Ischaemische Herzkrankheiten Akuter Herzmuskelinfafkt ------ Cerebrovaskulare Krankheiten Bronchitis, Emphysem und Asthma Leberzirrhose Untalle Suizid und Setbstoeschadigung Lungentuberkutose 2 11,9 2 10.9 0 1 1 4.4 0 2 0 0,7 0 0.1 1 3.5 1 3,2 0 0,3 0 0.2 7 9.7 5 7.9 1 3.7 0 1.9 2 2,2 4 7 0 3.5 0 0,9 23 31 _ - _ 40 43 _ _ 112 95 37 126 88 36 38.5 35 35.5 1 3 8 14.5 5 6.7 0 2,5 2 0.4 14 11.3 13 10,5 1 1.2 4 0.6 46 31,7 33 25 6 14.2 3 7 7 6.7 19 17.7 a 9.5 0 2.7 *) Uberschreiiung des 9S%*Vertrauensbereichs **) Uberschfeitung des 99e*-Venrauensberciehs (J. C. BAILAR: Significance Factors for (be Ratio of a Poisson Variable to its Expectation. Biometrics 20: 639*643. 1964) 105 111 36 62 84 622 138 138 89 822 164** 149*' 46 47 118 127 98 24 31,4 23 29.2 1 2,2 6 11.5 2 4,8 1 2,1 1 0,3 10 9.2 10 8.9 1 1.2 1 0.3 43 28 31 22 16 11.8 1 5.3 5 6.5 9 10.8 7 5.9 0 1,2 83 66 47 58 43 66 372 . 109 116 87 364 167** 154* 140 19 86 95 137 SAL O0Q07QA o^o -23- ab. Zbl Arbeitsmcd. 32 (I9S2) 2 Wnylchlorit Exposition u. Morialilnt 14 SMR acc. exposure duration foi workers from PVC processing (cohort 3) observation period Bcobachiungszeitraum 59 ICO Diagnose Gesamtmortalitat -- 12 13- 60 Beob.wert Erw.- wert SMR Beob,wert Erw.- wert SMR 45 39,5 114 112 109.8 102 61 - 120 Beob.wert Erw.- wert SMR 121 + Beob.wert Erw.- wert SMR 85 93,1 91" 118 137,3 86" 140-209 140*199 200-209 150-159 151 153 155 160-163 162 168 191 410-414 410 430-438 490-493 571 800-949 950-959 Oil Mafigne Tumoren der Organe und systematische Malignome Maligne Tumoren Tumoren des lymphatischen und haematopoetischen Gewebes Maligne Tumoren der ,, Verdauungs organe Maligne Tumoren des Magens Maligne Tumoren des DiCkdarms Maligne Tumoren der Leber Maligne Tumoren des respiralorischen Systems Maligne Tumoren der Trachea. Broncbien und Lunge Maligne Tumoren der Harnblasc Maligne Tumoren des Gehirns Ischaemische Herzkrankheiten Akuter Herzmuskelinfarkl Cerebrovaskulare Krankheiten Bronchitis. Emphysem und Asthma Leberzirrhose Unfalie Suizid und Seibstbeschadigung Lungentuberkulose 3 7,3 42 3 46 6,6 0 0.7 0 2.6 0 1.2 0 0.5" 0 0,07 _> 2 105 2 2 114 1,8 0 0.2' 0 0.1 6 112 6 5 119 4,6 -- 2 98 2.5 0 1,1 2 161 1.5 7 142 6,1 4 168 2,9 0 0.5 1 17 20.3 17 20,4 0 1.9 6 6.2 2 3.7 1 1.5 2 0.2 8 6.3 8 5.8 0 0.7 1' 0.3 31 18.5 20 14.5 9 6.3 3 3.8 3 4.2 9 12.9 6 6.5 0 1.4 68 96 85 63 95 1094* 147 159 336 195" 161 115 85 87 68 108 18 20.3 18 16.6 110 0 1.5 7 103 7,6 3 95 3.4 0 1.3 1 580 0.2 6 110 6 5 97 5,6 0 0.7 2 845' 0,3 23 17.1 157 18 13,5 152 5 69 7.5 0 3.6 3 68 3.7 6 89 8.2 1 24 4.6 0 1,3 1 24 32,0 22 29.9 2 2.1 2 11.9 2 5.2 0 2,1 0 0.3 9' 10,1 9 9.4 2 1,1 2 0.3 36 27.9 26. 22,2 7 . 11.4 1 5,7 6 5,9 10 8.3 4 5.3 0 1.6 80 18" 41 - 187 690 144' 132 64 19 116 138 90 ') Uberschreitung des 95<-Verlrauen5bereichs ) Uberschreitung des SS'/j-Vertrauensbereicns (J. C. BAILAR: Significance factors for the Raiio of a Poisson Variable to its Expectation. SAL Biometrics 20: 639-643. 1964) Tab. U: SMR nach Expositionsdauor bei Arbeiicn a us der PVC-Weitorverarbcitung (Koftorie Hi) 000070624 -24- ab co Vinyfrii ^Exposition u. Mortolnas 15* SMR |-------------- acc. age classes for processing \oonor -- workers from 24 25-- 34 Altcrsklnssen 35 -- 44 45- 54 ZM. Arbcinnied. M9S2) 2 55 - 64 CS * Beooachlung*. wen SMR BeoSachlungswert SMR Bcosachlungswen SMR Beobachlungswen SMR Beobachtungswert SMR Beob* achlungswen SMR ICO Diagnose Gesamtmonaiiiat Erwartungs- wen 6 8.5 94 Erwarlungswert Erwarlungswert Erwartungs- wert 28 102 44 101 6i 27,4 43.6 71.4 Erwarlungs- wen 85 106 ii7,i Erwar* tungs wen 91 H3 111.7 101 140- 209 140 - 199 200* 209 150- 159 1S1 153 155 160- 163 162 166 191 410 414 410 430* 438 490-493 571 600 949 950- 959 Oil Maligne Tumoren der Organe und systematised Malignome Maligna Tumoren Tumoren des lymphatischen unC haematepoenscnen Geweoes Maligne Tumoren der Vercauungsorgane und des Pernoneums Maligne Tumoren des Magens Maligne Tumoren des Diekdarms Maligne Tumoren der Leber Maligne Tumoren des respiratorischen Systems Maligne Tumoren der Trachea. Bronchien und Lunge Maligne Tumoren der Harnblase Maligne Tumoren des Gehirns iscnaemisehe Herjkrankheiien Akuler Her2mushelinlarkt Cereprovascuiare Krankheiten Bronchitis. Emphysem und Astnma Leberzirrhose Unlilie Sumd uno Sefbstoeschadigung Lungeniuberkuiose 1 287 0,5 1 476 0,3 0 0.2 0 0.05 0 0.02 0 0.02 _ 0 0,0007 0 -- 0.03 0 ,T 0,03 0 0.002 0 0.02 0 0.04 0 0.04 0 _. 0.05 0 0,03 0 -- 0,03 3 94 4.3 0 1.1 0_ 0.01 3 2.6 3 1.9 0 0.7 1 0,5 0 0.2 0 0.1 1 0,01 0 0.2 0 0.1 0 0,01 1 0.1 3 0.8 2 0.7 0 0.5 0 0.2 0 0.6 9 9.5 2 4.4 0 0.2 129 5 6.5 177 5.4 __ 0 1,1 216 2 2.2 _1 0.9 1 0.5 7710- 0 0.07 --2 1.2 1 1 0 0.2 964 0 0.3 431 e 5.5 312 8 4.9 0 1.3 0 0.5 --2 2.4 107 6 8.2 4 S3 5.1 0 0.8 96 115 _ 120 139 299 0.2 206 118 194 218 107 103 102 _ 10 15.7 10 14.4 0 1.3 1 6 0 2.7 0' 1 1 4 4.6 4 4.2 0 0.4 3 0.3 21 14.8 13 12.8 3.3 0 1.6 2 4.1 7 6 3 4.3 0 1.2 75 82 19 725 0.3 105 114 1099** 169* 122 33 _ 63 142 82 22 29.8 60 21 81 28,1 1 60 1.7 6 61 11 S 109 4.9 0 1.8 0 0.2 13 135 10.3 13 145 9.6 0 1 1 370 0.3 27 . 26 113 22 114 2l.l 9 110 9 1 21 5.1 150 5.2 3 72 4.9 107 3 0 1.5 21 26.6 20 25.4 1 \2 5 10.5] 1 4.8 0 1.9 1 84 84 91 51 23 506 78 8.2 6 84 7.5 2 181 1.2 0 nnfi 37 184" 22,3 24 169- 15.5 13 86 15. 3 47 6.8 107 3 4 2.6 . 1 162 306 0 1 `Oberschreilung Cos gS'A-Verirauensbereichs **Oberschreitung Ces 99A-Veruauensbereich (J. 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Transit Technical Library Theodore Duvekot July 21, 1983 SAL 000070626