Vinyl Chloride Workers Research Articles

Occupational exposure to vinyl chloride and cancer risk: a review of the epidemiologic literature.

Occupational exposure to vinyl chloride (VC) is causally related to liver angiosarcoma, whereas there is inconsistent epidemiologic evidence for other neoplasms. Two pooled analyses of worker cohorts from 56 plants in North America and Europe provide the most comprehensive and updated data on cancer risk among workers exposed to VC. These included over 22,000 workers, with a total of 640,000 person-years of observation, followed-up for up to 50 years. Overall, a total of 1,778 cancer deaths were observed versus 1,829.46 expected, corresponding to a standardized mortality ratio (SMR) of 0.97 (95% confidence interval (CI)=0.93-1.02). Excluding 71 confirmed angiosarcomas, there were 60 deaths from liver cancers versus 44.35 expected (SMR=1.35, 95% CI=1.03-1.74). Lung and laryngeal cancer mortality were significantly lower than expected (SMR=0.88 and 0.59, respectively). The SMRs for soft tissue sarcoma, brain, lymphoid and haematopoietic system cancers were not materially different from unity. Thus, the aggregate data from over 20,000 VC workers in North America and Europe exclude any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and haematopoietic neoplasms. There appears to be a slight excess of liver cancer other than angiosarcoma, which is difficult to interpret and is likely due to residual misclassification of angiosarcomas.

A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage

We have recently demonstrated a significant dose–response relationship between vinyl chloride exposure and mutant p53 biomarkers in humans. The aim of this study was to examine a common polymorphism in the DNA repair gene XRCC1 as a potential biomarker of susceptibility modifying this relationship, consistent with the known mechanism of production of p53 mutations via vinyl chloride-induced etheno-DNA adducts, which are repaired by XRCC1. A cohort of 211 French vinyl chloride workers were genotyped for the XRCC1 codon 399 polymorphism (CGG>CAG; Arg>Gln). Among the homozygous Arg–Arg individuals, 34% were biomarker positive compared with 47% in the heterozygous Arg–Gln individuals (adjusted odds ratio 1.73, 95% CI0.93–3.22) and 66% in the homozygous Gln–Gln individuals (adjusted odds ratio 3.95, 95% CI 1.68–9.28), with a significant trend for increasing Gln allele dosage (p=0.002). These preliminary results suggest that a common polymorphism in a DNA repair gene can be an important biomarker of susceptibility for chemically induced genetic damage.

Lung cancer risk in workers exposed to poly(vinyl chloride) dust: a nested case-referent study

Background: There have been few investigations of an association between poly(vinyl chloride) (PVC) dust exposure and an increase in lung cancer incidence, and their conclusions have been inconsistent. Aims: To...

Periportal fibrosis and other liver ultrasonography findings in vinyl chloride workers

Aims: To investigate the presence of liver lesions and their relation with vinyl chloride monomer (VCM) exposure or other personal risk factors, in workers involved in the production of VCM...

Plasma p53 protein and anti-p53 antibody expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of angiosarcoma of the liver (ASL), a rare tumor. Previously, a study of p53 gene mutations in tumors of VC-exposed workers found that 50% of liver angiosarcomas contained such mutations. Mutant p53 oncoprotein and anti-p53 antibodies can also be found in the sera of ASL patients and VC-exposed workers without cancer. Workers in Taiwan have also been exposed to VC, and some have contracted liver tumors. In this study, we used enzyme-linked immunosorbent assays to detect mutant p53 protein and anti-p53 antibodies in the plasma of VC-exposed workers in Taiwan. Thirty-three of 251 (13.2%) VC-workers tested positive for the p53 overexpression (10% with positive mutant p53 protein and 3.6% with positive anti-p53) in their plasma, but only 2 of 36 controls (5.6%) tested positive (2.8% with positive mutant p53 protein and 2.8% with positive anti-p53). There was a significant association between cumulative VC exposure concentration and positive p53 expression (P = 0.032) among VC workers after we adjusted for age, hepatitis, drinking, and smoking status. In summary, P53 overexpression (mutant p53 protein or anti-p53 antibody) can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma p53 overexpression and VC cumulative exposure concentration.

Plasma Asp13-Ki-ras oncoprotein expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of liver angiosarcoma, a rare tumor. Previously, more than 80% of VC workers with liver angiosarcoma have been found to have an Asp-13 c-Ki-ras oncogene mutation, and more than 50% of VC-exposed workers without liver tumors were found to have Asp13-Ki-ras oncoprotein in their plasma. Some workers in Taiwan had also been exposed to VC, and some have contracted liver tumors. In this study, we used enhanced chemiluminescence Western blotting to detect Asp13-p21-Ki-ras in the sera of VC-exposed workers in Taiwan. There were 14 of 113 (12.4%) VC workers positive for the Asp13-Ki-ras oncoprotein in plasma, but 0 of 18 controls were positive. There were 10 of 69 (14.5%) plasma-positives among the more highly exposed (> 1000 ppm-months) workers and 4 of 48 (9.1%) plasma-positives among the lesser exposed (< or = 1000 ppm-months). Compared with the unexposed controls, the odds ratios (and 95% confidence intervals [CI]) for plasma-positivity were 4.11 (95% CI = 0.21, 80.4) in the lower-exposed workers and 6.53 (95% CI = 0.37, 116.9) in the higher-exposed workers, and there was a linear trend between exposure and plasma-positivity (P = 0.073). After adjusting for age and drinking status, the odds ratios (and 95% CIs) were 1.64 (95% CI = 0.17, 15.8), and 2.65 (95% CI = 0.42, 16.8), respectively, and there was a significant linear trend between exposure and plasma-positivity (P = 0.048). In summary, Asp13-Ki-ras oncoprotein can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma oncoprotein expression and VC exposure.

Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1–2/2–2 genotypes was also significantly associated with an elevation of SCE frequency (9.5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1–2/2–2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1–2/2–2 genotypes, who also smoke, may have increased risk of DNA damage.

Molecular epidemiology of p53 protein mutations in workers exposed to vinyl chloride.

The production of mutations in cellular tumor suppressor genes such as p53 is involved in the development of many human cancers. These mutations result in the expression of mutant forms of the encoded p53 protein which can potentially serve as a biomarker for this carcinogenic process. Workers exposed to vinyl chloride who are at risk for the development of the sentinel neoplasm angiosarcoma of the liver represent a model population for the study of such a mutant p53 biomarker, since vinyl chloride is known to cause specific p53 mutations in persons with angiosarcoma of the liver. To determine the relation between vinyl chloride exposure and this p53 biomarker, the authors examined serum samples collected between 1987 and 1992 from a cohort of 225 French vinyl chloride workers and 111 unexposed controls (matched according to age, sex, race, smoking, and alcohol drinking) for the presence of mutant p53 protein, using an enzyme-linked immunosorbent assay. Stratification of the exposed workers by quartile of vinyl chloride exposure (in estimated ppm-years) yielded a statistically significant trend of increasing odds ratios for p53 biomarker seropositivity with increasing exposure. These results suggest that this serum biomarker for mutant p53 protein is related to vinyl chloride exposure and may be an early indicator of carcinogenic risk in exposed individuals.

Mutant p21ras in vinyl chloride exposed workers

The production of mutations in cellular oncogenes such as ras is involved in the development of many human cancers. These mutations result in the expression of mutant forms of the encoded p21 protein which can potentially serve as a biomarker for this carcinogenic process. Workers exposed to vinyl chloride (VC) who are at risk for the development of the sentinel neoplasm angiosarcoma of the liver (ASL) represent a model population for the study of such a mutant p21ras biomarker, since VC is known to cause a specific ras mutation in ASL. In order to determine the relationship between VC exposure and this biomarker, serum samples from a cohort of 225 French VC workers and 111 age-sex-race-smoking-drinking matched unexposed controls were examined for the presence of mutant p21ras by immunoblotting with a mouse monoclonal antibody specific for the mutant protein. Stratifying the exposed workers by degree of VC exposure in estimated ppm-years by quartiles yielded a statistically significant trend for increasing odds ratio for sero-positivity of the p21ras biomarker with increasing exposure. These results suggest that this serum biomarker is related to VC exposure and may be an early indicator of carcinogenic risk in exposed individuals.

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...

The computed tomographic appearances of angiosarcoma of the liver

The computed tomographic (CT) appearances are described in five vinyl chloride workers with hepatic angiosarcoma subsequently confirmed at post-mortem. The tumour was multifocal in four patients. Non-enhanced scans were available in four cases showing hypodense masses relative to background liver. Dynamic scanning during intravenous contrast injection was performed in all five patients showing peripheral or central foci of enhancement within the tumour. On delayed post-contrast scans performed in three patients the angiosarcoma became wholly or partly isodense compared to normal liver. The CT appearances of angiosarcoma of the liver are non-specific but are consistent with a vascular tumour, and the differential diagnosis is discussed. Due to the vascularity of angiosarcoma, liver biopsy may be hazardous and can be avoided when there is a history of exposure to vinyl chloride monomer and the CT findings are consistent with the diagnosis.

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).

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.

Tumors of the Liver, Other Than Primary Hepatocellular Carcinoma

Hepatic angiosarcoma is the second most common primary malignant neoplasm of the liver. Although comprising only 2 per cent of all hepatic primary tumors, it represents a major clinical problem because of its strong association with industrial vinyl chloride exposure and its incurability. Strict ceilings on the amount of exposure for vinyl chloride workers has reduced the incidence of this devastating tumor. In addition, recent chemotherapeutic trials have provided both improved performance status and prolonged survival in several patients.

Incidence of cancer among vinyl chloride and polyvinyl chloride workers: further evidence for an association with malignant melanoma.

In a previous report1 we presented results of a mor tality study in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride which gave sup port to the observations from animal studies2 that vinyl chloride (VCM) may act as a multicarcinogen in man. We report here our finding of two new cases of malignant melanoma of the skin in the extended fol low up period 1980-4 versus 0-3 expected, giving six cases versus IT expected overall. Salmon discussed the importance of considering that less specific tumours might also be induced by exposure to VCM, and that high background incidences of such tumours make it difficult to show an increased incidence.3 He found it difficult to dismiss the excess of malignant melanoma in the study population as being the result of confounding factors, owing to the lower back ground incidences and the fact that the confounding variables (race, sunlight exposure) are more connected with geography than with personal habits, and there fore less likely to vary between control and exposed populations. Salmon also suggested that exposure to ethylene dichloride should be taken into consideration in our study population since it had been used in the process on site,3 and he suggested that our data should be reviewed with exposure to ethylene dichlo ride in mind. Since there was an increase in production and in the number of employees during the work period in which members were recruited to the cohort, the observation period was short for some of the members.1 Associations between occupational exposure fac tors and malignant melanoma of the skin have been suggested by some authors. In a study based on a proportionate mortality analysis Thomas and Decoufle found increased mortality of malignant melanoma among white male pharmaceutical production workers.4 Alderson and Rushton found

Early detection and signs of hepatoangiosarcoma among vinyl chloride workers.

Health examinations of 108 workers exposed to vinyl chloride monomer (VCM) at a Japanese chemical plant were carried out in 1979. The polymerization of vinyl chloride was started at the plant in 1949. In this study, the highest concentration of VCM in autoclaves was determined to be 250 ppm in 1961. However, the workers at the plant had been exposed to higher concentrations of VCM several times before 1960. More recent VCM exposure was considered negligible. Examinations assessed data on age, height, weight, obesity index, sake consumption, VCM exposure concentration, latent period, cumulative exposure, ICG (indocyano green test), serum bilirubin, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), A1-P (alkaline phosphatase), GGT(gamma-glutamyl transpeptidase), ZTT (zinc turbidity test), LDH (lactate dehydrogenase), cholesterol, TTT (thymol turbidity test), A/G (albumin globulin ratio), and thrombocytes. Variation in VCM exposure did not affect tests of pigment excretion from the liver, such as ICG; thrombocytes; and enzyme activity (such as GPT); nor bilirubin or flocculation reaction in serum.

Incidence of cancer among vinyl chloride and polyvinyl chloride workers

Diagrams are unquestionably powerful tools. A multitude of studies investigate the relative usefulness of different types of diagrams (e.g. Larkin and Simon, 1987; Vessey and Galletta, 1991; Vessey and Conger, 1994; Jones and Schkade, 1995). However, analysis and research directed at empirically identifying and synthesizing basic components of diagram clarity, are rare. This study integrates isolated findings related to diagram clarity and experimentally investigates their application. The research utilized comes primarily from the Cognitive Information Processing (CIP) and Information Theory (IT) streams. Accordingly, the approach here is termed CIPIT. The set of CIPIT rules presented here represent a foundational framework for basic diagram clarity. The utility of the CIPIT rules are investigated experimentally via applying the CIPIT rules to one type of diagramming technique, the Data Flow Diagram (DFD). The experiment is carried out to investigate the clarity of a CIPIT-based DFD relative to a non-CIPIT DFD. Diagram clarity is measured objectively in terms of both speed of comprehension and the amount of comprehension. A questionnaire using likert-scale items is used to capture users' attitudes about the two diagrams. The results indicate a strong significant effect (increased clarity) for the CIPIT-based DFD.

Incidence of cancer among vinyl chloride and polyvinyl chloride workers.

The results of a follow up study of the incidence of cancer and the mortality in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride are presented. The study population was restricted to employees with more than one year's work experience in the study plant between 1950 and 1969 and the cohort was followed up from 1953 to the end of 1979. Twenty three new cases of cancer were observed compared with 20.2 expected; one case of liver angiosarcoma was found. Five cases of lung cancer were found (2.8 expected) and four cases of malignant melanoma of the skin were observed (0.8 expected). The possibility of a causal relationship between exposure to vinyl chloride and the development of malignant melanomas is discussed.

Epidemiologic problems associated with exposure to several agents.

Simultaneous exposure to many potentially hazardous agents in the environment is the rule, yet there have been few studies that have addressed the issue of interactions of these agents in modifying disease outcomes, even though such interactions may potentially be important in terms of policy-making. Epidemiological methods may be an important way to identify interaction effects, especially for chronic disease outcomes. Some examples of epidemiologic investigations of this problem are given, and a matrix method used to evaluate the contribution of nineteen chemicals to the risk of liver angiosarcoma in vinyl chloride workers is discussed.

Epidemiologic Problems Associated with Exposure to Several Agents

Simultaneous exposure to many potentially hazardous agents in the environment is the rule, yet there have been few studies that have addressed the issue of interactions of these agents in modifying disease outcomes, even though such interactions may potentially be important in terms of policy-making. Epidemiological methods may be an important way to identify interaction effects, especially for chronic disease outcomes. Some examples of epidemiologic investigations of this problem are given, and a matrix method used to evaluate the contribution of nineteen chemicals to the risk of liver angiosarcoma in vinyl chloride workers is discussed.