The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride: A systematic review and meta-analysis

Claudia Bolognesi, Marco Bruzzone, Marcello Ceppi, Micheline Kirsch-Volders

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

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 50 ppm 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 0.03–0.07 mg/m3. 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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalMutation Research - Reviews in Mutation Research
Volume774
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

Vinyl Chloride
Micronucleus Tests
Cytokinesis
Meta-Analysis
Lymphocytes
Population
Polyvinyl Chloride
Liver Neoplasms
China
Yugoslavia
Benchmarking
Hemangiosarcoma
DNA Adducts
Environmental Monitoring
Neoplasm Genes
Point Mutation
Carcinogens
Inhalation
India
Industry

Keywords

  • Biomonitoring
  • Carcinogenicity
  • Genotoxicity
  • Lymphocyte cytokinesis-block micronucleus
  • Systematic review
  • Vinyl chloride

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

@article{808a06e6af5b48b09a89fed4d0cde9f9,
title = "The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride: A systematic review and meta-analysis",
abstract = "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 50 ppm 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 0.03–0.07 mg/m3. 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.",
keywords = "Biomonitoring, Carcinogenicity, Genotoxicity, Lymphocyte cytokinesis-block micronucleus, Systematic review, Vinyl chloride",
author = "Claudia Bolognesi and Marco Bruzzone and Marcello Ceppi and Micheline Kirsch-Volders",
year = "2017",
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language = "English",
volume = "774",
pages = "1--11",
journal = "Mutation Research - Reviews in Mutation Research",
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T1 - The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride

T2 - A systematic review and meta-analysis

AU - Bolognesi, Claudia

AU - Bruzzone, Marco

AU - Ceppi, Marcello

AU - Kirsch-Volders, Micheline

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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 50 ppm 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 0.03–0.07 mg/m3. 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.

AB - 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 50 ppm 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 0.03–0.07 mg/m3. 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.

KW - Biomonitoring

KW - Carcinogenicity

KW - Genotoxicity

KW - Lymphocyte cytokinesis-block micronucleus

KW - Systematic review

KW - Vinyl chloride

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U2 - 10.1016/j.mrrev.2017.07.003

DO - 10.1016/j.mrrev.2017.07.003

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JO - Mutation Research - Reviews in Mutation Research

JF - Mutation Research - Reviews in Mutation Research

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