Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.     

Vinyl chloride exposure in a controlled industrial environment. A long-term mortality experience in 594 employees.

Vinyl chloride has been associated recently with findings of angiosarcoma in animals and man. The present study examines the mortality experience of individuals occupationally exposed to vinyl chloride and lesser amounts of vinylidene chloride and other compounds. Employees were grouped into four exposure categories according to the highest levels of vinyl chloride exposure experienced for at least one month. Although no angiosarcomas were found and there were no deaths due to any liver malignancy, the observed malignancy deaths exceeded the expected among workers in the high-exposure category. Fewer than expected malignancy deaths were observed in the remaining exposure catergories.     

Vinyl Chloride Exposure in a Controlled Industrial Environment

Vinyl chloride has beers associated recently with findings of angiosarcoma in animals and man. The present study examines the mortality experience of individuals occupationally exposed to vinyl chloride and lesser amounts of vinylidene chloride and other compounds.

Employees were grouped into four exposure categories according to the highest levels of vinyl chloride exposure experienced for at least one month. Although no angiosarcomas were found and there were no deaths due to any liver malignancy, the observed malignancy deaths exceeded the expected among workers in the high-exposure category. Fewer than expected malignancy deaths were observed in the remaining exposure categories.     

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.     

Mortality of workers exposed to methylene chloride employed at a plant producing cellulose triacetate film base.

OBJECTIVE: To study mortality among 1785 employees of a factory that produced cellulose triacetate film base at Brantham in the United Kingdom. Also, to investigate patterns of mortality after exposure to methylene chloride; in particular, mortality from liver and biliary tract cancer, lung cancer, pancreatic cancer, and cardiovascular disease. SUBJECTS AND METHODS: All male employees with a record of employment at the film factory in 1946-88. A total of 1473 subjects worked in jobs that entailed exposure to methylene chloride. The mean duration of exposure was nine years at 19 ppm (eight hour time weighted average). RESULTS: In the cohort, 334 deaths were identified up to 31 December 1994. Mortalities for the cohort were compared with national and local rates and expressed as standardised mortality ratios (SMR). In the subcohort of workers exposed to methylene chloride, substantially reduced mortalities compared with national and local rates were found for all causes, all cancers, and the principal cancer sites of interest. The significantly reduced lung cancer mortalities in exposed workers (SMR 48) seemed to reflect the restrictions on smoking at the workplace. In contrast, mortality from ischaemic heart disease in exposed workers, although lower than national rates (SMR 92), was slightly increased compared with local rates. However, mortality from ischaemic heart disease was lower in active employees (SMR 83) where a direct effect of exposure to methylene chloride should be concentrated. No in service mortality due to ischaemic heart disease was found in workers with the highest cumulative exposure (> or = 800 ppm-years). CONCLUSIONS: The study provided no indication that employment at the plant, or exposure to methylene chloride, had adversely affected the mortalities of workers.     

An industry-wide epidemiologic study of vinyl chloride workers, 1942-1982

The cohort consisted of 10,173 men who had worked for at least one year in jobs involving exposure to vinyl chloride prior to 1 January 1973. These men were employed at 37 plants in the U.S., belonging to 17 companies. Observation of the mortality experience of the cohort was updated from 31 December 1972 to 31 December 1982 (the study now covering 1942-1982). A total of 1,536 cohort members were identified as having died. The observed mortality, by cause, was compared with the expected based on U.S. mortality rates, standardized for age, race, and calendar time. Analyses by length of exposure, latency, age at first exposure, calendar year of first exposure, and type of products were performed. The study confirmed that the vinyl chloride workers experience a significant mortality excesses in angiosarcoma (15 deaths), cancer of the liver and biliary tract (SMR = 641), and cancer of the brain and other central nervous system (SMR = 180). In addition, the study also found a significant mortality excess in emphysema/chronic obstructive pulmonary disease (COPD) (SMR = 179). On the other hand, the study did not find any excess in either respiratory cancer or lymphatic and hematopoietic cancer. This study also found an increase in biliary tract cancers, independent from liver cancer.     

氯乙烯作业工人恶性肿瘤流行病学调查研究

目的 为了解氯乙烯作业工人恶性肿瘤发病情况。方法 采用回顾前瞻性观察法,对921名氯乙烯作业工人进行了40年死因流行病学调查。结果 男性接触组肝癌死亡率明显高于对照组。RR为2．16（P＜0．05）;接触组恶性肿瘤、肝癌的死亡也显著高于1994年全国城市居民恶性肿瘤的死亡率及1995年全国城市居民肝癌的死亡水平。SMR分别为1．8、29（P＜0．05）。在恶性肿瘤分类构成中,接触组肝癌居首位。结论 氯乙烯作业工人肝癌高发具有职业性特征。     

氯乙烯作业工人恶性肿瘤发病情况的流行病学调查

对全国12个城市的13个聚氯乙烯制造工人中5459名氯乙烯作业工人和6461名对照厂工人进行了从投产到1989年12月31日为止的恶性肿瘤发病情况的回顾性和前瞻性队列调查。结果表明,男工接触组肝癌的发病率、死亡率均显著高于对照组,男性肝癌的死亡率也显著高于我国中等城市男性肝癌的死亡率。在恶性肿瘤的分类构成中,接触组男工的肝癌居首位。接触组男工肝癌的发病年龄比对照组显著提前。     

An investigation of mortality from cancer and other causes of death among workers employed at an east Texas chemical plant

The cause-specific mortality of 2,510 males employed at an east Texas chemical plant was examined in a historical prospective study to evaluate a suspected increase in deaths from multiple myeloma and brain cancer. Potential exposures from chemicals, either used in manufacturing processes or produced during the study period 1952-1977, included the fuel additive tetraethyl lead, ethylene dibromide and dichloride, inorganic lead, and vinyl chloride monomer. Overall mortality for all workers (156 observed vs. 211.14 expected) and for workers first employed between 1952 and 1959 (131 observed vs. 167.33 expected) when tetraethyl lead was the single major product was lower than expected when compared to the United States general population. There were no significant increases in mortality from malignancies or other causes of death. The deficits may be due to the small number of total deaths, and the low power for detecting excess risk of mortality from multiple myeloma (Z1-beta = 27, alpha = .05), brain cancer (Z1-beta = 31, alpha = .05), or other rare causes of death; lack of complete workplace exposure data for production workers; and the absence of historical measurements on the extent of environmental exposure to tetraethyl lead and other chemicals.     

Exposures to silica mixed dust and cohort mortality study in tin mines: exposure-response analysis and risk assessment of lung cancer

BACKGROUND: Mineral dusts that contain crystalline silica have been associated directly or indirectly with the development of pneumoconiosis or silicosis, non-malignant respiratory diseases, lung cancer, and other diseases. The health impacts on workers with silica mixed dust exposure in tin mines and dose-response relationships between cumulative dust exposure and the mortality from lung cancer are investigated. METHODS: A cohort of 7,837 workers registered in the employment records in 4 Chinese tin mines between 1972 and 1974 was identified for this study and the mortality follow-up was traced through 1994. Of the cohort, the cause of death was ascertained for 1,061 (97%) of the 1,094 deceased workers. Standardized mortality ratios (SMRs) were calculated for all workers, non-exposed workers, and dust-exposed workers with different exposure levels, silicotics, and non-silicotics based on Chinese national rates. RESULTS: The mortality from all causes in four tin mines was nearly the same as the national mortality. Malignant neoplasm, cerebrovascular disease, and cardiovascular disease accounted for 68.6% of all deaths. Mortality excess from lung cancer, liver cancer, all malignant diseases, and non-malignant respiratory diseases was observed among dust-exposed workers; a 50-fold excess of pneumoconiosis was observed. There was an upward trend for SMRs of lung cancer was noted from no exposure to low, medium, and high exposure levels (SMRs=1.29, 2.65, 2.66, 3.33). The shape of the exposure-response curve for risk of lung cancer at high exposure levels was inconsistent in these four mines. CONCLUSIONS: The findings indicated a positive dose-response relation between exposure to cumulative dust and the mortality of lung cancer. High arsenic content in dust particles, together with crystalline silica, may play an important role in causing increased mortality from lung cancer.     

Epidemiologic study of workers exposed to vinyl chloride in Porto Marghera: mortality update

The investigation describes mortality of vinyl chloride exposed workers in the Montedison-Enichem plant located in Porto Marghera, near Venice, Italy. A total of 1658 workers employed from start of production (1950), present in 1956 or successively hired until 1985, were followed up between 01.01.1973 and 31.07.1999, for a total of 41.037 person years at risk: 248 deaths were observed. Mortality from all causes compared with regional population was lower than expected, (SMR 0.75; 90% CI 0.68-0.83) and from all malignant neoplasms similar to expected (SMR 0.94; 90% CI 0.81-1.09). SMR for primary liver cancer was significantly increased (SMR 2.78 90% CI 1.86-4.14). In the first year since leaving employment observed mortality was significantly above the null value for all causes (SMR 2.76; 90% CI 1.94-3.91), all malignant neoplasms (SMR 1.89; 90% CI 0.97-3.92) and cardiovascular diseases (SMR 2.37; 90% CI 1.13-4.95). Mortality rates for liver angiosarcoma (6 cases) increased with latency (trend test x 2 (1df) = 25.20 p < 0.001) and cumulative exposure (trend test x 2 (1df) = 61.00 p < 0.001), there were no cases with duration of employment less than 12 years, latency less than 10 years and for cumulative exposure less than 2.379 ppm-years. Mortality rates for hepatocellular carcinoma (12 cases) and liver cirrhosis (20 cases) showed a similar pattern for cumulative exposure. Observed mortality from lung cancer was higher than expected among those workers whose only job title was bagger. In the analysis accounting for latency, age and calendar period the RR for only bagger was 2.31 (90% CI 1.15-4.61). Mortality pattern for all causes, all malignancies and cardiovascular disease increased by time since employment, as expected in presence of a particularly strong Healthy Worker Effect (HWE). These results and the increased SMR values during the first year since leaving employment indicate that workers were selected into employment on the basis of good health conditions and early selective removal of weaker ones followed. The study results confirm the causal relationship between VCM exposure and liver angiosarcoma, and add supplementary evidence in favour of a causal explanation of the excess risk for hepatocellular carcinoma and liver cirrhosis as well as lung cancer among only baggers.     

Increased morbidity odds ratio of primary liver cancer and cirrhosis of the liver among vinyl chloride monomer workers

OBJECTIVES: To determine if there is an increased risk of admission to hospital for various diseases among vinyl chloride monomer (VCM) workers. METHODS: 2224 workers with occupational exposure to VCM were identified for occurrence of disease based on a search of hospital computer files on labour insurance. These data were compared with those of workers manufacturing optical equipment and motorcycles from 1 January 1985 to 31 March 1994. Cardiovascular and cerebrovascular diseases were used as reference diseases, and the age adjusted morbidity odds ratio (MOR) was calculated. RESULTS: A significantly increased risk of admission to hospital among VCM workers due to primary liver cancer (MOR 4.5-6.5), cirrhosis of the liver (MOR 1.7- 2.1), and other chronic diseases (MOR 1.5-2.0) was found. There were eight cases of primary liver cancer, all with heavy previous exposure to VCM. Another four cases of hepatoma in polyvinyl chloride (PVC) workers were found in the death registry. Ten out of 11 cases of hepatoma, with detailed medical information, were carriers of hepatitis B virus. The average latent period (20 years) was not different from other studies. Alternative agents of primary liver cancer were largely ruled out, suggesting that the combination of hepatitis B and VCM may lead to primary liver cancer. CONCLUSION: There is an increased risk of primary liver cancer in workers exposed to VCM, although the incomplete coverage of the Labor Insurance Bureau data warrants cautious interpretation of the results. Further study exploring the synergistic effects of VCM and hepatitis B is also indicated.     

氯乙烯作业工人恶性肿瘤发病情况的前瞻性流行病学调查

对全国范围内12个城市的13个大、中型聚氯乙烯生产工厂5 291名接触氯乙烯的工人,及6 276名对照工人,进行了从1982-01-01～1989-12-31为止的前瞻性流行病学调查。结果没有发现肝血管肉瘤患者,但接触组男工肝癌的死亡率显著高于我国中等城市男性居民肝癌的死亡率(P<0.05),在恶性肿瘤的分类构成中,接触组男工以肝癌居首位,而且肝癌的发病年龄比对照组显著提前。     

Mortality among workers exposed to cutting oil mist: update of previous reports

BACKGROUND: Earlier reports of the mortality experience of this cohort of automotive workers followed from 1938 to 1967 who were exposed to cutting oil mist noted an excess of gastrointestinal cancer. The present report describes the mortality experience of these workers followed for mortality through 1980. METHODS: Cause-specific standardized mortality ratios were calculated by comparing the observed number of deaths to the expected numbers based on rates for the U.S. male population. RESULTS: The SMRs for liver and biliary tract, and testicular cancers were significantly elevated. Among the subset of workers with heavy oil mist exposure, SMRs were significantly elevated for cancers of the lung and testis, and for Hodgkin's disease. The risk of death due to lung cancer was greatest among workers with heavy exposure to oil mist employed for 15 or more years. Mortality due to stomach cancer was in excess among workers with heavy exposure to oil mist who were employed for 5 or more years. There were significant excesses of deaths due to asthma and emphysema. CONCLUSIONS: Further studies with information on the presence of contaminants and additives in oil mists will help elucidate the relationship between oil mist exposure and cancer.     

Mortality surveillance in a large chemical company: the Union Carbide Corporation experience, 1974-1983

The mortality experience of 88,000 Union Carbide Corporation employees from 1974 to 1983 is presented using a population-based surveillance system. The study included many long-term employees, with most deaths contributed by those retired or terminated. The total population exhibited 30% lower mortality overall and 10% lower cancer mortality, as compared with the general U.S. population. Excesses of benign neoplasms and malignant melanoma of the skin were observed in both hourly and salaried males. Mortality rates for lymphosarcoma and reticulosarcoma were significantly elevated due to higher rates among hourly male employees and a cluster in one location. This same location also exhibited an excess of liver cancer associated with vinyl chloride operations. There were no other significant excesses in the hourly male workers and fewer deaths than expected due to brain cancer, respiratory cancer, and nonmalignant respiratory diseases. Salaried, and particularly hourly, women experienced favorable mortality, although for the women, time since hire was relatively short. Location-specific findings were similar to what had been observed in the company's previously conducted cohort studies. Future value lies in the development of a database that will have greater power to address possible effects of past exposures and outcomes related to more recent lower level exposures.     

Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites.

OBJECTIVES: To study the incidence of angiosarcoma of the liver in England and Wales 1979-86 and Scotland 1975-87. To investigate whether any non-occupational neighbourhood cases occurred near a vinyl chloride site. METHODS: This is a geographical study of incident cases among the general population of Great Britain. Diagnosis of angiosarcoma of the liver was based mainly on the national cancer registry, the world register of cases among vinyl chloride workers, and the register of cases (including histological review) maintained by the Health and Safety Executive. Proximity (< 10 km) of residence to a vinyl chloride site was based on postcode of address at the time of diagnosis. RESULTS: 55 cases were ascribed to angiosarcoma of the liver in England and Wales with a further six cases in Scotland (annual incidence in Great Britain from all sources of around 1.4 cases per 10 million population). There were two cases with documented exposure to Thorotrast, and 10 cases among vinyl chloride workers. There were no vinyl chloride sites in Scotland. Among the 25 cases in England and Wales with histological diagnosis after review by a panel of pathologists, only 15 were confirmed as angiosarcoma, and one of the two Scottish cases after histological review was also confirmed. Overall, 11 cases ascribed to angiosarcoma were resident within 10 km of a vinyl chloride site; nine were vinyl chloride workers, one further case on histological review was not considered to have been correctly diagnosed as angiosarcoma, and the remaining case, confirmed as angiosarcoma, was employed at a vinyl chloride factory during the late 1950s, although not as a vinyl chloride worker. CONCLUSION: The incidence of angiosarcoma of the liver in Great Britain remains extremely rare. The one confirmed case in a non-vinyl chloride worker within 10 km of a site must nevertheless be presumed to have been exposed to vinyl chloride in the workplace. In the period of study, there were no confirmed non-occupationally exposed cases of angiosarcoma among residents living near a vinyl chloride site in Great Britain.     

Historical cohort study of 10 109 men in the North American vinyl chloride industry, 1942-72: update of cancer mortality to 31 December 1995

OBJECTIVES—To update and assess mortality from neoplasms to 31 December 1995 among 10 109 men employed in a job exposed to vinyl chloride for at least 1 year between 1942 and 1972 at any of 37 North American factories. Previous analyses indicated associations between employment in vinyl production and increased mortality risk from cancers of the liver and biliary tract, due to increased mortality from angiosarcoma of the liver, and brain cancer.
METHODS—Standardised mortality ratio (SMR) analyses, overall and stratified by several work related variables, were conducted with United States and state reference rates. Cox's proportional hazards models and stratified log rank tests were used to further assess occupational factors.
RESULTS—895 of 3191 deaths (28%) were from malignant neoplasms, 505 since the previous update to the end of 1982. Mortality from all causes showed a deficit (SMR 83, 95% confidence interval (95% CI) 80 to 86), whereas mortality from all cancers combined was similar to state referent rates. Mortality from cancers of the liver and biliary tract was clearly increased (SMR 359, 95% CI 284 to 446). Modest excesses of brain cancer (SMR 142, 95% CI 100 to 197) and cancer of connective and soft tissue (SMR 270, 95% CI 139 to 472) were found. Stratified SMR and Cox's proportional hazard analyses supported associations with age at first exposure, duration of exposure, and year of first exposure for cancers of the liver and soft tissues, but not the brain.
CONCLUSIONS—Excess mortality risk from cancer of the liver and biliary tract, largely due to angiosarcoma, continues. Risk of mortality from brain cancer has attenuated, but its relation with exposure to vinyl chloride remains unclear. A potentially work related excess of deaths from cancer of connective and soft tissue was found for the first time, but was based on few cancers of assorted histology.


Keywords: vinyl chloride; angiosarcoma; liver; brain; connective tissue; soft tissue; neoplasms     

A collaborative study of cancer incidence and mortality among vinyl chloride workers

A large European multicentric cohort study has been coordinated by the International Agency for Research on Cancer with the objectives of investigating the dose-response relationship between liver cancer and exposure to vinyl chloride and assessing cancer risk for sites other than the liver. A nearly threefold increase in liver cancer was detected on the basis of 24 observed deaths and 8.4 expected (standardized mortality ratio 286, 95% confidence interval 186-425). The excess from liver cancer was clearly related to time since first exposure, duration of employment, and estimated ranked and quantitative exposures. Other cancer sites investigated on the basis of a priori hypotheses were either not in excess (lung) or apparently unrelated to the exposure variables (brain and lymphoma).     

某陶瓷厂工人癌症死亡分析

本文调查了湖南界牌陶瓷厂２３４５例工人１９７２－１９９４年的死因，追访到１９９４年底，共死亡３９３人，全死因标化死亡率不比全国居民平均水平超高，队列研究不支持接尘与全癌，肺癌，肝癌及胃癌有关，但陶工尘肺患者中，除肺癌死亡较多外，其它恶性肿瘤未见高发。病例对照研究不支持接尘及尘肺与肺癌及肝癌相关，仅提示吸是肺癌发病的危险因素。     

Mortality among employees of lead battery plants and lead-producing plants, 1947-1980

Two cohorts of male lead workers, 4 519 battery plant workers and 2 300 lead production workers, all of whom had been employed for at least one year during the period 1 January 1946 through 31 December 1970, were observed for mortality during the 34 years from 1 January 1947 through 31 December 1980. Vital status as of the closing date was determined for 94.7% of the former group and 91.6% of the latter. There were 1 718 deaths in the first cohort and 621 in the second. Mortality from all causes combined was significantly greater than expected in each cohort, the standardized mortality ratio (SMR) being 107 and 113, respectively. Among the battery plant workers the greater than expected mortality rate resulted in large part from a significant number of excess deaths from malignant neoplasms (SMR 113), other hypertensive disease (mainly renal) (SMR 320), chronic nephritis (SMR 222), and a group of ill-defined conditions (SMR 355). Among the lead production workers the pattern was similar, with a significant number of excess deaths from other hypertensive disease (SMR 475), hypertensive heart disease (SMR 203), chronic nephritis (SMR 265), and ill-defined conditions (SMR 214). There was also a significant excess of deaths from external causes (SMR 143). The SMR for total malignancies was 113, but this value was not significantly elevated at the 5% level. In neither cohort were deaths from cerebrovascular disease in significant excess, the SMR being 93 and 132, respectively. A proportionate mortality analysis showed that the excess deaths from cerebrovascular disease and from hypertensive heart disease among smelter workers were in part due to the high proportion of nonwhites in the smelter populations. The stomach, liver, and lungs were the sites responsible for most excess cancer deaths in both cohorts, but the elevated SMR values were statistically significant only for gastric and lung cancers in battery plant workers. There were no excess deaths from malignancies of the kidney, brain, or lymphopoietic system in either cohort. It is impossible to relate the observed mortality to levels of lead exposure; because of meager quantitative information prior to 1960. It is known that past exposures had been very high. Ethnicity, diet, alcohol, and cigarette smoking could not be ruled out as possible confounding etiologic factors for the cancer deaths.