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The vinyl chloride monomer (VCM), a common raw material in the plastics industry, is one of the environmental pollutants to which humans are mostly exposed. Thiodiglycolic acid (TDGA) in human urine is a specific biomarker of its exposure. TDGA plays an important role in understanding the relationships between exposure to the VCM and the identification of subgroups that are at increased risk for disease diagnosis. Therefore, its detection is of great significance. Here, we designed and established a ratiometric fluorescent sensor for TDGA by using Eu 3+ as a bridge connecting the covalent organic framework (COF) and the energy donor molecule 2,6-dipicolinic acid (DPA) and named it DPA/Eu@PY-DHPB-COF-COOH. The sensor not only possesses the advantages of a ratiometric fluorescent sensor that can provide built-in self-calibration to correct a variety of target-independent factors but also presents high selectivity and high sensitivity. Currently, there are only a few reports on the detection of TDGA, and to the extent of our knowledge, this report is the first work on the detection of TDGA based on a COF system; so, it has an important reference value and lays a solid foundation for designing advanced sensors of TDGA.

In the late 20th century, fetal protection policies barred women from hundreds of thousands of industrial jobs on the pretext that if women became pregnant, their fetuses might be harmed by workplace exposure to toxic chemicals. Beginning in the 1970s, these policies set off a decades-long contest between the chemical industry, government agencies, and the judicial system over how to balance the uncertain reproductive health risks against sex discrimination. This article revives the subject of reproductive health and workplace protections through a historical case study of fetal protection policies at Firestone Plastics, a leader in the postwar vinyl chloride industry. I use formerly secret industry documents to argue that Firestone used scientific uncertainty and gender essentialism to skirt new regulatory pressures and minimize corporate liability. Ultimately, fetal protection policies stymied innovative regulatory efforts to protect all workers-not just women-from reproductive hazards in the workplace. ( Am J Public Health . 2022;112(2):271-276. https://doi.org/10.2105/AJPH.2021.306539).

Objective: To review articles that evaluated the prevalence of Raynaud's phenomenon of occupational origin., Methods: The search for articles was carried out in the Medline (via PubMed), Embase, Web of Science, Scientific Electronic Library Online (SciELO), and Latin America and Caribbean Health Sciences Literature (Lilacs) databases., Results: 64 articles were obtained from the electronic search; 18 articles met the eligibility criteria. All studies discussed the exposure to vibrations in the upper limbs. In 6 of them, the thermal issue was directly or indirectly addressed. No studies have addressed exposure to vinyl chloride., Conclusio: In general, a higher prevalence of Raynaud's phenomenon was found among vibratory tool operators compared to non-exposed workers, with an increase in the number of cases the higher the level of vibration and the time of exposure. Cold is a triggering and aggravating factor of the Raynaud phenomenon and seems to play an important role in the emergence of vascular manifestations of the hand-arm vibration syndrome.

Background: Occupational and experimental studies have revealed that high vinyl chloride monomer (VCM) exposure is associated with non-alcoholic fatty liver disease (NAFLD). Epidemiological study reported that children living near a petrochemical complex have elevated exposure levels of urinary thiodiglycolic acid (TDGA), a potential VCM biomarker. However, no studies on the association of urinary TDGA exposure with NAFLD in children are available., Aim: To assess the association of pediatric NAFLD with urinary TDGA exposure in school-aged children living near a petrochemical complex., Materials and Methods: In total, 261 school-aged children (aged 6-13 years) living near a petrochemical complex were recruited during October 2013 to September 2014. First morning spot urine was sampled for analyzing urinary TDGA through liquid chromatography-tandem mass spectrometry. Ultrasonography and serum alanine aminotransferase (ALT) were examined in each participant. NAFLD was diagnosed as recommended by the North American and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN). Risk for NAFLD with urinary TDGA exposure in children was evaluated using a multivariate logistic regression model., Results: The percentage of children with NAFLD NASPGHAN and NAFLD ESPGHAN were 9.6% and 11.5%, respectively. Median levels (μg/g creatinine) of urinary TDGA of children with NAFLD NASPGHAN (vs non-NAFLD NASPGHAN ) and NAFLD ESPGHAN (vs non-NAFLD ESPGHAN ) were 118.0 (vs 96.6) and 113.1 (vs 96.5), respectively. Participants in the highest urinary TDGA quartile (Q4: ≥160.0 μg/g creatinine) had a significantly increased risk (odds ratio [OR] = 4.95; 95% confidence interval [CI] = 1.15-21.38; P = 0.032) and dose-response trend (P trend  = 0.045) for NAFLD NASPGHAN compared with those in the lowest urinary TDGA quartile (Q1: <35.4 μg/g creatinine) after adjustment for age, gender, BMI, triglycerides, HOMA-IR and distance of elementary schools from the petrochemical complex. Participants in the Q4 had borderline significantly increased risk (OR = 3.45; 95% CI = 0.89-13.42; P = 0.074) correlated with NAFLD ESPGHAN compared with those in the Q1 after adjustment for confounders., Conclusion: Our findings support the hypothesis that children exposed to higher urinary TDGA levels significantly increased pediatric NAFLD risk. Serum ALT levels can be a useful predictor for screening children's NAFLD in field studies. Large and longitudinal studies are warranted to elucidate the association., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vinyl chloride (VC), an abundant environmental contaminant causes steatohepatitis at high levels, but is considered safe at lower (i.e., sub-OSHA) levels. However, we have previously shown that even lower VC levels exacerbate experimental nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD). Mitochondrial oxidative injury and subsequent metabolic dysfunction appeared to play key roles in mediating this interaction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) serves as a key line of defense against endogenous and exogenous reactive aldehydes. The current study therefore tests the hypothesis that allosteric activation of ALDH2 with Alda-1 will protect against VC-enhanced NAFLD. Mice were exposed to low VC concentrations (<1 ppm), or room air for 6 h/day, 5 days/week for 12 weeks, while on HFD or low-fat control diet (LFD). Some mice received Alda-1 (20 mg/kg i.p., 3 × /week) for the last 3 weeks of diet/VC exposure. Indices of liver injury, oxidative stress, metabolic and mitochondrial (dys)function were measured. As observed previously, low-dose VC did not cause liver injury in control mice; while liver injury caused by HFD was enhanced by VC. VC decreased hepatic ALDH2 activity of mice fed HFD. Alda-1 attenuated oxidative stress, liver injury, and dysmetabolism in mice exposed to HFD+VC under these conditions. Importantly, alterations in mitochondrial function caused by VC and HFD were diminished by Alda-1. Previous studies have indicated that liver injury caused by HFD is mediated, at least in part, by enhanced mitochondrial autophagy (mitophagy). Here, Alda-1 suppressed PINK1/PARKIN-mediated mitophagy. Taken together, these results support the hypothesis that ALDH2 is a critical defense against mitochondrial injury caused by VC in experimental NAFLD. The ALDH2 activator Alda-1 conferred protection against liver damage under these conditions, most likely via increasing clearance of aldehydes and preserving mitochondrial respiratory function., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Occupational exposure to vinyl chloride monomer (VCM) has been established as a cause of hepatocellular carcinoma (HCC) and liver angiosarcoma (ASL). However, some controversy remains due to conflicting results on liver cirrhosis, and to evidence on HCC based on few confirmed cases. The aim of the study is to clarify the association between VCM exposure and mortality from liver diseases., Methods: In a cohort of 1658 workers involved in VCM production and polymerization, Poisson regression was adopted to estimate rate ratios (RR) across categories of VCM exposure for mortality due to ASL (n = 9), HCC (n = 31) confirmed by histological/clinical records, and the combination of deaths from liver cirrhosis and from liver cancer with clinical/histological evidence of cirrhosis (n = 63)., Results: Cumulative VCM exposure was associated with study outcomes; RRs in the highest compared to the lowest exposure category were: ASL 91.1 (95%Confidence Interval 16.8-497), HCC 5.52 (2.03-15.0), liver cirrhosis 2.60 (1.19-5.67)., Conclusions: The risk of death from liver cirrhosis, as well as from HCC in the largest available series of confirmed cases, increased with VCM exposure., (© 2018 Wiley Periodicals, Inc.)

Thiodiglycolic acid (TDGA) is a major metabolite of vinyl chloride monomer (VCM), and it has been suggested as an exposure biomarker for VCM. The validity of this biomarker when the level of VCM is less than 5 ppm, however, is questionable. The objective of this article is to evaluate the feasibility of using urinary TDGA as a biomarker of VCM exposure in a community health risk assessment setting where the concentration of VCM in air is typically very low (likely below 1 ppm). To achieve this objective, we examine the fraction of urinary TDGA associated with different levels of VCM exposures of three studies from different countries, using estimations of the TDGA metabolite predicted by a PBPK model. It is demonstrated that differences in background TDGA have considerable effect on the adequacy of TDGA as a biomarker of VCM. We conclude that, in a community health assessment setting, TDGA should not be used as an exposure biomarker for VCM without having a proper control group, and a PBPK model can be used first to determine whether or not the amount of TDGA in urine is of concern., (Copyright © 2018. Published by Elsevier Inc.)

Obesity, usually caused by high fat diets (HFD), is a major public health issue worldwide, causing obesity associated cardiomyopathy. Moreover, the environmental toxicant vinyl chloride (VC) can exacerbate HFD-induced fatty liver disease. However, whether VC serves to enhance obesity-associated cardiomyopathy remains unclear. This study aims to investigate the interaction of western diet (WD) containing relatively low fat (42%) with VC on cardiac remodeling and its underling mechanisms. Adult male C57BL/6J mice were exposed to WD coinhalation of low-dose VC (<1 ppm/d) for 12 weeks. Results showed that WD feeding for 12 weeks caused slight cardiac systolic dysfunction without significant hypertrophy or fibrosis, even with VC. Nevertheless, WD upregulated NF-κB function and expression of IL-1β and PAI-1, while VC showed no significant impact on these effects. In contrast, WD together with VC significantly increased the expression of CHOP and TGF-β1, key markers for endoplasmic reticulum stress and profibrotic cytokine, respectively. In summary, exposure to low-dose of environmental toxicant VC while a WD is consumed for a relatively short time does not have significant impact on cardiac remodeling except for a mild systolic dysfunction of the heart.

Objective: To explore the relationship between relative telomere length (RTL) and chromosomal damage represented by micronucleus (MN) frequencies among vinyl chloride monomer (VCM) -exposed workers., Methods: A group of 126 VCM-exposed workers, 60 internal controls, and 25 external controls were examined for RTL by Quantitative polymerase chain reaction and MN frequencies by cytokinesis-block micronucleus test. Cumulative exposure dose was used to estimate the exposure of VCM-exposed workers., Results: The RTL were significantly shorter in exposed workers and internal controls than in external controls. The exposed workers had significantly increased MN frequencies than both control groups. Additionally, MN frequencies were negatively associated with RTL in VCM-exposed group., Conclusions: VCM exposure may alter telomere length, which could be a potential biomarker of susceptibility to chromosomal damage.

Objective: To evaluate mortality risks of angiosarcoma of the liver (ASL), primary hepatocellular carcinoma (HCC) and other cancers among 9951 men employed between 1942 and 1972 at 35 US vinyl chloride (VC) or polyvinyl chloride plants followed for mortality through 31 December 2013., Methods: SMR and time-dependent Cox proportional hazards analyses were used to evaluate mortality risks by cumulative VC exposure., Results: Liver cancer mortality was elevated (SMR=2.87, 95% CI 2.40 to 3.40), and ASL and HCC were strongly associated with cumulative VC exposure ≥865 parts per million-years (ppm-years) (ASL: HR=36.3, 95% CI 13.1 to 100.5; and HCC: HR=5.3, 95% CI 1.6 to 17.7 for ≥2271 ppm-years). Excess deaths due to connective and soft tissue cancers (SMR=2.43, 95% CI 1.48 to 3.75), mesothelioma (SMR=2.29, 95% CI 1.18 to 4.00) and explosions (SMR=3.43, 95% CI 1.25 to 7.47) were seen. Mortalities due to melanoma, brain cancer, lung cancer and non-Hodgkin's lymphoma were not increased or associated with VC exposure., Conclusion: The association between VC and ASL first reported in this cohort 44 years ago persisted and was strongest among workers most highly exposed. VC exposure also was associated with HCC mortality, although it remains possible that misdiagnosis of early ASLs influenced findings., Competing Interests: Competing interests: All authors are employed by Ramboll Environ US Corporation. Ramboll Environ received financial support from the American Chemistry Council to conduct the study described in the manuscript. Ramboll Environ also has received financial support from, and contracts with, the American Chemistry Council for work on scientific topics unrelated to the submitted manuscript., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Vinyl chloride (VC) is widely used in industry in the production of polyvinyl chloride (PVC), which is used to manufacture a large variety of materials. VC was classified as a known (Group 1) human carcinogen by IARC on the basis of increased risk for liver angiosarcoma and hepatocellular cancer, and the carcinogenicity of VC was shown to be mediated by a genotoxic mechanism. Following inhalation, the compound is rapidly absorbed and metabolized in the liver to the electrophilic metabolites chloroethylene-oxide and chloroacetaldehyde, which form DNA adducts that can be processed into point mutations in cancer-related genes detected in humans and rats exposed to VC. A number of genotoxicity biomarkers were applied in workers exposed to VC to detect early biological responses associated with the carcinogenesis process. The present systematic review analyzed the published studies in which the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) was applied in VC-exposed subjects. Thirteen out of fifteen retrieved studies performed in China showed increased MN frequencies (FR 1.92-3.98) associated with increased cumulative exposure or employment time. Twofold and more than threefold increases were detected in PVC-exposed workers exposed to a mean of 50ppm of VC in the former Yugoslavia and in South India, respectively. The meta-analysis of MN frequency from six eligible studies confirmed this tendency (pooled MR 2.32 - 95% CI 1.64-3.27). The benchmark dose lower limit for 10% excess risk (BMDL 10) calculated from three studies resulted in an estimated exposure limit of 0.03-0.07mg/m 3 . Overall the results of this review showed the need for further studies, especially because PVC products from China may contain high levels of uncoupled VCM that could represent a source of exposure to workers and consumers. Moreover, the results underline the importance of re-evaluating the recommended exposure limits using new biomonitoring methods in addition to MN., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Strong experimental and clinical evidences have definitely linked occupational vinyl chloride exposure to development of angiosarcoma of the liver. In contrast, despite the International Agency for Research on Cancer having included vinyl chloride among the causes of hepatocellular carcinoma, the association between vinyl chloride exposure and hepatocellular carcinoma remains debated. This issue is relevant, because occupational exposure to high levels of vinyl chloride may still occur. We report a unique case of sequential occurrences of hepatocellular carcinoma and angiosarcoma of the liver, in a vinyl chloride-exposed worker without cirrhosis and any known risk factor for chronic liver disease. Both the hepatocellular carcinoma and the surrounding normal liver showed micronucleus formation, which reflects genotoxic effect of vinyl chloride. Angiosarcoma showed a KRAS G12D point mutation, which is considered to be characteristic of vinyl chloride-induced angiosarcoma. This case supports the pathogenic role of vinyl chloride in both hepatocellular carcinoma and angiosarcoma development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the article there are presented the results of the evaluation of cytokine profile in males working in the production of vinyl chloride (trained workers without signs of disorders of the neuropsychic status and persons with early signs of neurointoxication with vinyl chloride, characterized by asthenic (emotional lability) disorder with the autonomic dysfunction). There are established differences of pro- and anti-inflammatory responses in workers in dependence on the severity of disorders of the neuropsychic status. The most pronounced imbalance of cytokines was in workers with initial manifestations of neurointoxication with vinyl chloride. The increase in the concentration of pro-inflammatory cytokines (IL-1β, IL-8, TNF-α) in trained employees without signs of disorders of the neuropsychic status is the one of the early and sensitive indices characterizing the formation ofthe body's resistance to exposure of adverse factors of production.

Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas (PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan-Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006., Methods: Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o-toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios., Results: Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89-6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non-Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long-term workers exposed to carbon disulfide and shift work for 4 years or more., Conclusions: Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors., (© 2014 Wiley Periodicals, Inc.)

Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM)., Materials and Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups., Results: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05)., Conclusions: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.

This paper considers the features of disorders of immunity in chronic exposure to vinyl chloride at work and in experimental animals. It is shown that one of the earliest and most sensitive indicators of the formation of the resistance of the organism employed in the manufacture of vinyl chloride, are: IgM, IL-1beta, TNF-alpha, autoantibodies to neurospecific proteins (S-100, Vd-Ca channels and DNA).

Background: Vinyl chloride monomer (VCM) is a colorless gas under room temperature and has been mostly used to produce polyvinyl chloride (PVC) since the 1970s. It is classified by the International Agency of Research on Cancer (IARC) as a known human carcinogen (Group 1). In this study, genetic damage in VCM workers was evaluated in relation to their occupational cumulative exposure to VCM., Methods: Cytokinesis-block micronucleus assay was conducted in 229 VCM workers and 138 controls to detect chromosome damage in peripheral blood lymphocytes. The cumulative exposure dose (CED) of VCM was calculated based on the job type and duration of each worker and the workplace VCM concentration. Dose-response relationships between VCM CED and micronucleus frequency or chromosomal damage were evaluated, and benchmark doses (BMDs) estimated., Results: Dose-response relationships between VCM CED and chromosomal damage were obtained. The 95% lower confidence bound of BMD of VCM CED was 2.86 mg/m(3) -year for both genders combined, leading to an estimated exposure limit of 0.072 mg/m(3) assuming a work life of 40 years., Conclusions: VCM exposure may induce chromosomal damage at occupational exposure levels below the Chinese national occupational health standard. Further research is needed to better understand micronuclei as biomarker of VCM genotoxicity. Better dose-response assessment and BMD estimation are desirable in order to improve the quantification of occupational exposure limits for VCM with respect to non-cancer risk., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To evaluate whether base excision repair gene polymorphisms contributed to susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM)., Methods: Cytokinesis block micronucleus test was performed on 185 VCM-exposed workers to detect chromosomal damage in peripheral lymphocytes. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of TDG, PARP1, and APE1 genes. Univariate and multivariate Poisson regression analysis was performed., Results: There was a 1.198-fold increased micronucleus frequency for individuals carrying TDG 199Gly/Ser + Ser/Ser genotypes compared with those carrying Gly/Gly genotype (P < 0.05). Individuals with the combined genotypes of TDG 199Gly/Ser + Ser/Ser and APE1 64Ile/Val + Val/Val had a significantly increased micronucleus frequency compared with those carrying wild-type genotypes for both genes., Conclusion: VCM-exposed workers carrying TDG 199Gly/Ser + Ser/Ser genotypes were susceptible to chromosomal damage. A combination of TDG Gly199Ser and APE1 Ile64Val polymorphisms may modify the risk of chromosomal damage.

We analyze mechanisms of moral disengagement used to eliminate moral consequences by industries whose products or production practices are harmful to human health. Moral disengagement removes the restraint of self-censure from harmful practices. Moral self-sanctions can be selectively disengaged from harmful activities by investing them with socially worthy purposes, sanitizing and exonerating them, displacing and diffusing responsibility, minimizing or disputing harmful consequences, making advantageous comparisons, and disparaging and blaming critics and victims. Internal industry documents and public statements related to the research activities of these industries were coded for modes of moral disengagement by the tobacco, lead, vinyl chloride (VC), and silicosis-producing industries. All but one of the modes of moral disengagement were used by each of these industries. We present possible safeguards designed to protect the integrity of research.

Objective: To investigate the association between genetic polymorphisms in phase I and phase II metabolism genes and DNA damage in peripheral blood lymphocytes of workers exposed to vinyl chloride monomer (VCM)., Methods: 87 workers occupationally exposed to VCM were investigated. DNA damage in peripheral blood lymphocytes was measured by Comet Assay; the workers were divided into case, control groups based on the comet frequency. Genotypes of CYP2E1 (rs3813867) were identified by the PCR-RFLP, null genotypes of GSTT1 and GSTM1 were detected by PCR. The genotype of GSTP1 (rs947894), CYP1A1 (rs1048943, rs4646903) and UGT1A6 (rs6759892, rs1105879, rs4124874, rs3755319, rs887829, rs4148323) were tested by the TaqMan PCR method., Results: The distribution of the c1c1 and c1c2 + c2c2 genotype of CYP2E1 (rs3813867), AA and AG + GG genotype of GSTP1 (rs947894), AA and AC + CC genotype of UGT1A6 (rs1105879) were significantly different in DNA damage group and control group by chi2 test (P = 0.029, P = 0.004 and P = 0.002, respectively). Multiple logistic regression analysis showed that the individuals carrying GSTP1 (rs947894) AG + GG genotypes had 13.393-fold (95% CI: 2.410-74.431, P < 0.01) increased risk of DNA damage in comparison with those with GSTP1 AA genotypes, and individuals carrying UGT1A6 (rs1105879) AC + CC genotypes had 0.064-fold (95% CI: 0.006-0.637, P < 0.05) decreased risk of DNA damage in comparison with those with UGT1A6 (rs1105879) AA genotypes. Haplotypes analysis of polymorphisms in UGT1A6 showed that the frequencies of TCCTAG haplotype in the controls were significant higher than those in the cases (P < 0.05)., Conclusion: The subjects carrying GSTP1rs947894 AG/GG genotypes and UGT1A6 rsl105879 AA genotypes could be more susceptible to VCM-induced DNA damage. UGT1A6 TCCTAG haplotype may be a protective genetic factor for DNA damage in VCM-exposed workers.

Background: The production of vinyl chloride (VC) and polyvinyl chloride (PVC) involves the use of various chemicals, some known to be toxic and potentially or definitely carcinogenic. The related potential risk often has not been properly investigated. Updated cancer mortality among different subgroups of workers employed in a VC-PVC production plant located in Porto Marghera (Italy) was re-analyzed using an internal reference group of workers with low (or null) exposure to VC., Methods: Mortality of 1658 male workers was analyzed by Poisson regression. Relative risks (RRs) and 95% confidence intervals (CIs) for blue collar workers and their specific subgroups of PVC baggers, PVC compound, autoclave and other blue collar workers were calculated using technicians and clerks as an internal reference group. The follow-up covered the period 1972-1999., Results: Significantly increased mortality rates were observed for all causes of death among the whole blue collar workforce (RR = 1.55; 95% CI = 1.03-2.35; 229 deaths), PVC baggers (1.72; 95% CI = 1.04-2.83; 49 deaths) and PVC compound workers (1.71; 95% CI = 1.09-2.67; 72 deaths). Liver cancer, including angiosarcoma, was increased among autoclave workers (9.57; 95% CI = 3.71-24.68; 7 deaths) and cardiovascular diseases among PVC baggers (2.25; 95% CI = 1.08-4.70; 12 deaths). Hemolymphopoietic system tumors, leukemias and lymphomas prevalently, were found only among exposed workers, with 4, 4 and 6 deaths observed among PVC baggers, PVC compound and other blue collar workers, respectively. An excess of lung cancer was found among PVC baggers., Conclusion: This cohort analysis, based on internal comparison, confirmed previously reported specific risk excesses for liver tumors and liver cirrhosis among autoclave workers and for lung cancer among PVC baggers, and revealed PVC compound workers as a possible new at risk group for all causes, all tumors and for liver and lung tumors. In conclusion, RRs for all causes of death and all tumors were increased among all blue collar workers.

Morphofunctional disturbances in rats affected vinyl chloride in remote period of intoxication. The presented data concern influence of inhalation impact of vinyl chloride on nervous system of white rats in remote period.

The study was conducted by Judicial Policy investigations of Prosecution's Office. The event was connected by a professional founded suspicion disease of a pharmaceutical worker. First information coming from the Authority indicated a chloride vinyl monomer (CVM) exposure. We applied a chemical risk assessment method to estimate real professional exposure. The method was based on the productive cycle, physical and chemical and toxicological properties. The method combined to environmental data permitted to formulate etiological hypothesis. The worker during drugs packaging was exposed to CVM and vinylidene chloride (CVDM) caused by blister warming and by glue deposition. We explain the evaluations by which we could consider the pollutant different distribution in workplaces.

In a four-facility occupational epidemiology study of chloroprene monomer and polymer production workers, the chloroprene (CD) and vinyl chloride monomer (VCM) exposures were modeled for plant specific job title classes. In two facilities an acetylene-based process was used and in the other two plants only a butadiene-based process was used in the monomer synthesis. In the Acetylene process VCM was an undesirable by-product to be removed. In the newer butadiene-based process, VCM was not involved and the exposures to CD were considerably lower than they were in the earlier years. One of the limiting factors was the operator rotation within a number of job titles. This rotation and inability to differentiate between job titles subsumed in job classifications recorded in the work histories required an exposure classification scheme based on an order of magnitude separation of exposure classes. In the four facilities with considerable variation in the mix of the production methods, the CD exposures were remarkably similar in both calculated and measured values. The reductions in exposures were much more dependent upon the improvement of the production methods, rather than deliberate exposure control for occupational hygiene considerations. This is reasonable since the exposures were generally lower than the coeval exposure limits and/or guidelines. The estimated exposures were less than 100 ppm in the pre-1960 era and less than 10 ppm in the 1960-1980 era, less than 1 ppm 1980-1990 era and less than 0.5 ppm thereafter. The exposures were categorized in four classes for VCM and six classes for CD. The characteristic class exposure values were used to cumulate individual exposures over time with a quantification of the potential range for exposures that are reasonably certain to ascribe correct ranking to job classes.

As part of an historical cohort study to investigate the mortality experience of industrial workers exposed to chloroprene (CD) and other substances, including vinyl chloride monomer (VC), we analyzed mortality from all cancers combined, respiratory system (RSC) and liver cancer in relation to CD and VC exposures. Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)). Historical exposures for individual workers were estimated quantitatively for CD and VC. For sites L, M, P and G, respectively, average intensity of CD exposures (median value of exposed workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures (ppm years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively, average intensity of VC exposures (median value of exposed workers in ppm) was 1.54 and 0.03 and median cumulative exposures (ppm years) were 1.54 and 0.094. We performed relative risk (RR) regression modeling to investigate the dependence of the internal cohort rates for all cancers combined, RSC and liver cancer on combinations of the categorical CD or VC exposure measures with adjustment for potential confounding factors. We categorized exposure measures into approximate quartiles based on the distribution of deaths from all cancers combined. We also considered 5- and 15-year lagged exposure measures and adjusted some RR models for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking history. All modeling was site-specific to account for exposure heterogeneity. We also computed exposure category-specific standardized mortality ratios (SMRs) to assess absolute mortality rates. With the exception of a one statistically significant association with duration of exposure to CD and all cancers combined in plant M, we observed no evidence of a positive association with all cancers, RSC or liver cancer and exposure to CD and/or VC using both the unlagged and lagged exposure measures: duration, average intensity or cumulative exposure to CD or VC; time since first CD or VC exposure; and duration of CD exposure or time since first CD exposure in presence or absence of VC exposure. We observed elevated and statistically significantly elevated RRs for some analysis subgroups, but these were due to inordinately low death rates in the baseline categories. With the possible exception of all cancer mortality in plant G, our additional adjustment of RRs for pay type revealed no evidence of positive confounding by smoking. We conclude that exposures to CD or VC at the levels encountered in the four study sites do not elevate mortality risks from all cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of general mortality patterns among the CD cohort reported in our companion paper [G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips, Mortality patterns among industrial workers exposed to chloroprene and other substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for publication].

We conducted an historical cohort study to investigate the mortality experience of industrial workers potentially exposed to chloroprene (CD) and other substances, including vinyl chloride (VC), with emphasis on cancer mortality, including respiratory system (RSC) and liver. In 1999, the International Agency for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B); VC was classified in 1987 as a known human carcinogen (Group 1). Subjects were 12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern Ireland (n=4849) and Grenoble, France (n=717)), with earliest CD production dates ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the acetylene process that produced VC exposures. We determined vital status through 2000 for 95% of subjects and cause of death for 95% of the deaths. Historical exposures for individual workers were estimated quantitatively for CD and VC. Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M) to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national and regional standard populations) in relation to selected demographic, work history and exposure factors. We used worker pay type (white or blue collar) as a rough surrogate for lifetime smoking history. For the combined cohort, SMRs (95% CIs) for all causes combined, all cancers combined, RSC and liver cancer were, respectively, 0.72 (0.69-0.74), 0.73 (0.68-0.78), 0.75 (0.67-0.84) and 0.72 (0.43-1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers combined: 0.75 (0.69-0.80), 0.68 (0.56-0.80), 0.68 (0.47-0.95) and 0.59 (0.36-0.91); for RSC: 0.75 (0.66-0.85), 0.79 (0.58-1.05), 0.62 (0.32-1.09) and 0.85 (0.41-1.56); for liver cancer: 0.90 (0.53-1.44) (17 deaths), 0.24 (0.01-1.34) (1 death), 0.0 (0-2.39) (no deaths) and 0.56 (0.01-3.12) (1 death). Among all workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66-0.76); for RSC: 0.75 (0.67-0.84); for liver cancer: 0.71 (0.42-1.14). We also observed no increased mortality risks among cohort subgroups defined by race, gender, worker pay type, worker service type (short/long term), time period, year of hire, age at hire, duration of employment, the time since first employment, and CD or VC exposure status (never/ever exposed). In summary, our study has many strengths and is the most definitive study of the human carcinogenic potential of exposure to CD conducted to date. We conclude that persons exposed to chloroprene or vinyl chloride at the levels encountered in the four study sites did not have elevated risks of mortality from any of the causes of death examined, including all cancers combined and lung and liver cancer, the cancer sites of a priori interest. This conclusion is corroborated by our detailed analyses of mortality in relation to qualitative and quantitative exposures to CD and VC at each of the four study sites, reported in our companion paper (Marsh et al., submitted for publication).

To expand a cohort of chemical workers in the Kanawha Valley, we conducted a study of 33,225 workers who were employed at three locations between 1940 and 1999. We observed no increase in overall cancer mortality. Higher risk estimates were observed for lymphosarcoma and reticulosarcoma among hourly employees who worked at the Institute or South Charleston locations. This finding was limited to men hired before 1960. We observed no new cases of angiosarcoma of the liver, a cause of death previously reported in association with vinyl chloride production at the South Charleston location. Specific risk factors for lymphosarcoma and reticulosarcoma have not been identified in previous targeted studies of this population and it is unlikely that additional cause-specific research will elucidate the etiology. Updates of the entire cohort will continue and can be used as a comparison population for chemical specific studies within these three plants.

Objective: The objective of this study was to examine the presence of mutant-p53 protein (p53Ag) and antibodies to p53 protein (p53Ab) in a population of workers exposed to vinyl chloride (VC)., Method: We have investigated the presence of two cancer markers in the plasma of 151 subjects exposed to varying concentrations of VC (4-2823 ppm). The investigation took place in two sessions: in 1999, the analysis was limited to p53Ab, and in 2000, the analysis was repeated and extended to include also the mutant-p53Ag. The available information on the subjects in this study includes age, total years of employment in the VC polymerization industry, exposure concentration, results of abdominal ultrasonogram, hepatitis status, smoking and alcohol drinking status, and clinical records. Logistic regression analyses were performed to calculate the association between prevalence of positivity for p53Ab or mutant-p53Ag and cumulative VC exposure concentration after adjustment for confounding factors. t test and chi analyses were performed to test significant differences among groups., Results: Three (1.9%) of the 151 workers exposed to VC resulted seropositive for the mutant-p53Ag and five (3.3%) for the p53Ab. All seropositive subjects are distributed in the highest exposure classes (>1000 ppm). No seropositivity was found among controls. The stratified relationship between seropositivity and exposure appeared statistically significant (chi = 23.65 for mutant-p53Ag and 30.35 for p53Ab)., Conclusions: revealing its presence in subjects having a history of VC exposure greater than 1000 ppm. On the basis of this study, and the clinical experience of the authors, the presence of a minimum threshold for the carcinogenic effects of VC is hypothesized.

Objective: To explore the relationship between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of metabolizing enzymes of VCM., Methods: Comet assay was employed to detect DNA damage, the workers were divided into two groups based on the status of DNA damage. Case-control design was used to investigate the relationship between the genetic polymorphisms of metabolizing enzymes and DNA damage. Genotypes of CYP2E1 c1/c2 and mEH4 His139Arg were identified by the PCR-RFLP, null genotypes of GST T1 and GST M1 were detected by PCR., Results: The genotypes of CYP2E1 c1c2 and c2c2 were significantly associated with DNA damages (P < 0.01). A prominent risk increasing of DNA damage was observed for those individuals having a high or low VCM exposure and possessing the CYP2E1 c1c2 and c2c2 genotypes (OR 4.92, 95% CI 1.35-13.85 and OR 2.57, 95% CI 1.01-6.59)., Conclusion: Cumulative exposure dose and polymorphism of metabolizing enzymes may modulate the DNA damage of VCM-exposed workers. possessing the CYP2E1 c1c2 and c2c2 genotypes (OR 4.92, 95% CI 1.35-13.85 and OR 2.57, 95% CI 1.01-6.59)., Conclusion: Cumulative exposure dose and polymorphism of metabolizing enzymes may modulate the DNA damage of VCM-exposed workers.

Background: Wegener granulomatosis is a chronic inflammatory autoimmune disease of unknown etiology. The sporadic occurrence, lack of familial or genetic associations, and rising incidence suggest possible exposure to environmental agents as causative for this disease., Objective: The objective of this study was to examine possible environmental triggers of Wegener granulomatosis., Methods: While conducting an environmental survey of potential precipitants of Wegener granulomatosis on a cohort of patients seen at Doylestown Hospital and at the University of Pennsylvania, we identified a cluster of cases in the Dublin, Pennsylvania, region. Through hospital records and patient contacts, we located 7 cases diagnosed in a 3-year period within a 10-mile radius of an Environmental Protection Agency (EPA) Superfund toxic waste site. The radius of inclusion represents a population of approximately 50,000 individuals. Assuming complete ascertainment of cases--which is unlikely given the methods used to acquire patients--the prevalence is 2- to 4-fold greater than the expected rate of 3 per 100,000. We identified toxins at or above "action level" within the demarcated geographic region using published data from the EPA. Furthermore, we queried patients regarding their particular chemical exposures., Results: These patients with Wegener granulomatosis were possibly exposed to high levels of trichloroethylene (TCE), vinyl chloride, methyl tertiary-butyl ether (MTBE), dichloroethene (DCE), and chromic acid from several industrial waste sites within the area. Additionally, these patients reported a total of greater than 30 possible exposures, including the aforesaid chemical contaminants. Three of 5 patients whose water source is known had well water that exposed them to industrial runoff and necessitated EPA intervention., Conclusion: This data, along with other epidemiologic studies, suggest possible toxic exposures as potentially correctable risk factors for Wegener granulomatosis. We encourage clinicians to seek data that suggests an unusual environmental exposure and to solicit information that might implicate an industrial source for these exposures.

Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)-induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case-referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman's synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm times years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28-2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13-1.69). The joint effect of VCM exposure above 2,500 ppm times years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6-8,553) for HCC and 752 (95% CI, 55.3-10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm times years and viral hepatitis infection was 210 (95% CI, 7.13-6,203) for HCC and 80.5 (95% CI, 3.67-1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection.

Several industry-based cohort studies have addressed the risk of lung cancer following exposure to vinyl chloride, acrylonitrile and styrene, with inconsistent results and usually without smoking adjustment. These exposures are addressed here in a large case-control study with full adjustment for smoking. Almost 6000 subjects were included in a case-control study conducted in seven European countries. For each job they held, local experts assessed the exposure to a number of occupational agents, including vinyl chloride, acrylonitrile and styrene, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected. The odds ratio (OR) for ever exposure to vinyl chloride was 1.05 (95% confidence interval, CI: 0.68-1.62) and a modest, non-significant increase in the risk of lung cancer was found in the highest exposed subgroup. The OR for ever exposure to acrylonitrile was 2.20 (95% CI: 1.11-4.36) with a positive dose-response relationship between estimated cumulative exposure and lung cancer risk. No association between exposure to styrene and lung cancer risk was found. In conclusion, we cannot exclude a weak association between occupational exposure to vinyl chloride and lung cancer risk. Exposure to acrylonitrile was associated in our study with risk of lung cancer. Exposure to styrene does not seem to increase lung cancer risk., (Copyright 2004 Kluwer Academic Publishers)

Aims: To study the synergistic effect of occupational chemical exposure and hepatitis virus infection on serum aminotransferase activity., Methods: A total of 568 male workers who were employed in five polyvinyl chloride (PVC) or four vinyl chloride monomer (VCM) manufacturing factories were studied. Information relating to current job title, alcohol consumption, and cigarette smoking was obtained. Exposure level of chemical mixtures was classified by hygienic effect (a summation of personal time weighted average/reference permissible exposure level of each chemical) into high, moderate, and low exposure groups. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-hepatitis C antibody were assayed., Results: Hepatitis virus infection and increased body mass index were associated with abnormal serum aminotransferase activity. In workers with hepatitis virus infection, those with high exposure had a higher prevalence of abnormal AST and ALT compared to low exposure; among those without hepatitis virus infection, the differences of prevalence of abnormal AST and ALT were not significant between different chemical exposure groups. There was a significant trend of increasing risks of increased AST and ALT in moderate and high exposure groups with hepatitis virus infection. Such a synergistic effect was more prominent among HBeAg-positive workers., Conclusions: Mixed exposures to 1,2-ethylene dichloride and VCM have a positive synergistic effect with hepatitis virus infection on liver damage. Assessment of fitness for work should be considered in workers with hepatitis B and C infection, when they have potential exposure to hepatotoxins in the workplace.

Past studies have reported an excess of angiosarcoma of the liver and brain cancer at a polymer production plant in Louisville, Kentucky. Although angiosarcoma has clearly been linked to vinyl chloride exposure, the cause of the brain cancer excess has been uncertain. We conducted case-cohort and case-control studies of both conditions in relation to chemicals used in polyvinyl chloride and nitrile rubber production. Angiosarcoma was strongly associated with vinyl chloride exposure but not with other chemicals used in production. Brain cancer was highest in workers hired prior to 1950 but was not associated with vinyl chloride or other specific exposures or production processes. This brain cancer cluster is similar to those reported in other industries in this generation of workers, the specific cause remaining unknown.

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.

Studies of overlapping cohorts in the United States have shown an excess mortality from brain cancer in vinyl chloride (VC)-exposed workers. One plant located in Louisville, Kentucky, is included in many of these studies. We separated this plant from the large US cohort and re-analyzed the mortality experience. Louisville experienced significantly elevated liver (standardized mortality analyses [SMR] = 400) and brain cancer (SMR = 229) mortality. Liver cancer mortality remained significantly elevated (SMR = 344) in the remaining cohort; however, brain cancer mortality was markedly reduced (SMR = 112) when Louisville was removed. In contrast with liver cancer, a preliminary review of work assignments did not suggest that the brain cancer excess was related to VC exposure. The Louisville brain cancer cluster has had a significant impact on the reported literature. Although unrelated to VC, the cause of this cluster remains uncertain.

Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

Urinary 8-hydroxydeoxyguanosine (8-OHdG) DNA adduct has been used as a biomarker in epidemiological studies. However, the determinants for urinary 8-OHdG have not been clearly identified. We tested urinary 8-OHdG levels in 205 male workers who had been exposed to vinyl chloride monomer (VCM). Epidemiological information was obtained by an interviewer-administered questionnaire. Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV) were also determined by immunoassay. Plasma antioxidants including Vitamins A and E, alpha- and beta-carotenes were assayed by high performance liquid chromatography. Median of urinary 8-OHdG level was 9.8 ng/mg creatinine (range, 1.4-60.1). Multiple linear regression analysis showed that alcohol drinkers had higher urinary 8-OHdG than those who did not, but there was no dose-response between the amount of alcohol consumption and urinary 8-OHdG. Workers with positive HBsAg, anti-HCV and elevated plasma Vitamin A level were independently associated with higher levels of urinary 8-OHdG, whereas age, smoking, body mass index, plasma alpha- and beta-carotenes, Vitamin E levels, or VCM exposure did not show such an association. The results suggest that active inflammation of hepatitis B and C, alcohol consumption and higher Vitamin A level can induce oxidative stress. Thus, we conclude that potential determinants need to be considered in epidemiological studies when urinary 8-OHdG is used as a biomarker.