The ex vivo L-CBMN assay detects significant human exposure to butadiene

Claudia Bolognesi, Micheline Kirsch-Volders

Research output: Contribution to journalArticle

Abstract

1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism. The available biomonitoring studies in workers occupationally exposed to BD, considering different genetic endpoints, do not allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The present systematic review retrieves and analyzes the published studies on the application of the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven studies on BD exposure and one study on exposure to a mixture of compounds in a styrene-butadiene tire manufacturing plant. Four studies carried out in Europe related to heterogeneous groups of workers exposed in BD monomer or polymer manufacturing and processing industries, reporting mean individual exposure levels below 3ppm, failed to find any increase of MN frequency. Three studies, including mixed groups of workers involved in different stages of the production and manufacturing of BD in China, show increased MN frequencies associated with the intensity of the exposure, with a relevant positive response (FR=2.29) when the mean cumulative dose was estimated as 266ppm/year. These results are consistent with the data on the exposure-response curve for total leukemia mortality showing no increase for cumulative exposure less than or equal to 200 BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome loss, events involved in induction of leukemia, seems to be a promising biomarker for cancer risk induced by BD.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalMutation Research
Volume770
Issue numberPt A
DOIs
Publication statusPublished - Nov 30 2016

Fingerprint

DNA
1,3-butadiene
Leukemia
Synthetic Resins
Elastomers
Chromosome Breakage
Environmental Pollutants
Micronucleus Tests
Styrene
Cytokinesis
Environmental Monitoring
Epoxy Compounds
Tumor Biomarkers
Carcinogens
DNA Damage
Rodentia
China
Polymers
Chromosomes
Lymphocytes

Keywords

  • Review
  • Journal Article

Cite this

The ex vivo L-CBMN assay detects significant human exposure to butadiene. / Bolognesi, Claudia; Kirsch-Volders, Micheline.

In: Mutation Research, Vol. 770, No. Pt A, 30.11.2016, p. 73-83.

Research output: Contribution to journalArticle

Bolognesi, Claudia ; Kirsch-Volders, Micheline. / The ex vivo L-CBMN assay detects significant human exposure to butadiene. In: Mutation Research. 2016 ; Vol. 770, No. Pt A. pp. 73-83.
@article{1736f2ba544b4118a81cbd8293e55dac,
title = "The ex vivo L-CBMN assay detects significant human exposure to butadiene",
abstract = "1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism. The available biomonitoring studies in workers occupationally exposed to BD, considering different genetic endpoints, do not allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The present systematic review retrieves and analyzes the published studies on the application of the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven studies on BD exposure and one study on exposure to a mixture of compounds in a styrene-butadiene tire manufacturing plant. Four studies carried out in Europe related to heterogeneous groups of workers exposed in BD monomer or polymer manufacturing and processing industries, reporting mean individual exposure levels below 3ppm, failed to find any increase of MN frequency. Three studies, including mixed groups of workers involved in different stages of the production and manufacturing of BD in China, show increased MN frequencies associated with the intensity of the exposure, with a relevant positive response (FR=2.29) when the mean cumulative dose was estimated as 266ppm/year. These results are consistent with the data on the exposure-response curve for total leukemia mortality showing no increase for cumulative exposure less than or equal to 200 BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome loss, events involved in induction of leukemia, seems to be a promising biomarker for cancer risk induced by BD.",
keywords = "Review, Journal Article",
author = "Claudia Bolognesi and Micheline Kirsch-Volders",
note = "Copyright {\^A}{\circledC} 2016 Elsevier B.V. All rights reserved.",
year = "2016",
month = "11",
day = "30",
doi = "10.1016/j.mrrev.2016.04.001",
language = "English",
volume = "770",
pages = "73--83",
journal = "Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis",
issn = "0027-5107",
publisher = "Elsevier",
number = "Pt A",

}

TY - JOUR

T1 - The ex vivo L-CBMN assay detects significant human exposure to butadiene

AU - Bolognesi, Claudia

AU - Kirsch-Volders, Micheline

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/11/30

Y1 - 2016/11/30

N2 - 1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism. The available biomonitoring studies in workers occupationally exposed to BD, considering different genetic endpoints, do not allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The present systematic review retrieves and analyzes the published studies on the application of the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven studies on BD exposure and one study on exposure to a mixture of compounds in a styrene-butadiene tire manufacturing plant. Four studies carried out in Europe related to heterogeneous groups of workers exposed in BD monomer or polymer manufacturing and processing industries, reporting mean individual exposure levels below 3ppm, failed to find any increase of MN frequency. Three studies, including mixed groups of workers involved in different stages of the production and manufacturing of BD in China, show increased MN frequencies associated with the intensity of the exposure, with a relevant positive response (FR=2.29) when the mean cumulative dose was estimated as 266ppm/year. These results are consistent with the data on the exposure-response curve for total leukemia mortality showing no increase for cumulative exposure less than or equal to 200 BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome loss, events involved in induction of leukemia, seems to be a promising biomarker for cancer risk induced by BD.

AB - 1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in rodents revealed widely different BD carcinogenic/mutagenic potency in rat and mice, associated to differences in BD metabolism. The available biomonitoring studies in workers occupationally exposed to BD, considering different genetic endpoints, do not allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The present systematic review retrieves and analyzes the published studies on the application of the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven studies on BD exposure and one study on exposure to a mixture of compounds in a styrene-butadiene tire manufacturing plant. Four studies carried out in Europe related to heterogeneous groups of workers exposed in BD monomer or polymer manufacturing and processing industries, reporting mean individual exposure levels below 3ppm, failed to find any increase of MN frequency. Three studies, including mixed groups of workers involved in different stages of the production and manufacturing of BD in China, show increased MN frequencies associated with the intensity of the exposure, with a relevant positive response (FR=2.29) when the mean cumulative dose was estimated as 266ppm/year. These results are consistent with the data on the exposure-response curve for total leukemia mortality showing no increase for cumulative exposure less than or equal to 200 BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome loss, events involved in induction of leukemia, seems to be a promising biomarker for cancer risk induced by BD.

KW - Review

KW - Journal Article

U2 - 10.1016/j.mrrev.2016.04.001

DO - 10.1016/j.mrrev.2016.04.001

M3 - Article

C2 - 27894692

VL - 770

SP - 73

EP - 83

JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

SN - 0027-5107

IS - Pt A

ER -