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Published on: April 26, 2018
1,3-Butadiene: II. Genotoxicity profile.
Richard J Albertini1, M Leigh Carson, Christopher R Kirman
1Pathology Department, College of Medicine, University of Vermont, Burlington, Vermont, USA.
Critical Reviews in Toxicology
|September 28, 2010
Summary
1,3-Butadiene (BD) is mutagenic and carcinogenic due to its metabolites, 1,2-epoxy-3-butene (EB), 1,2-dihydroxy-3,4-epoxybutane (EBD), and 1,2,3,4-diepoxybutane (DEB). DEB is the most potent mutagen, causing gene deletions and chromosome aberrations.
Area of Science:
- Toxicology
- Genetics
- Environmental Health
Background:
- 1,3-Butadiene (BD) is a significant industrial chemical with known mutagenic and carcinogenic properties.
- Its electrophilic metabolites, including 1,2-epoxy-3-butene (EB), 1,2-dihydroxy-3,4-epoxybutane (EBD), and 1,2,3,4-diepoxybutane (DEB), are implicated in its toxicity.
- These metabolites are DNA-reactive, forming adducts and exhibiting genotoxicity.
Purpose of the Study:
- To investigate the genotoxicity of 1,3-butadiene metabolites.
- To compare the mutagenic potencies and mechanisms of EB, EBD, and DEB.
- To explore species-specific differences in 1,3-butadiene metabolism and toxicity, particularly between mice and rats, and to assess human exposure risks.
Main Methods:
- In vitro and in vivo genotoxicity assays were used to evaluate the mutagenicity of BD metabolites.
- Relative potencies of DEB, EB, and EBD were determined.
- Species-specific production of DEB and its correlation with observed mutagenicity and carcinogenicity were analyzed.
- Human exposure data and mutation studies were reviewed.
Main Results:
- DEB demonstrated significantly higher mutagenic potency (DEB >> EB > EBD) and induced gene deletions and chromosome aberrations.
- Greater DEB production in mice compared to rats likely explains higher BD mutagenicity and carcinogenicity in mice.
- In vivo chromosome mutations were not observed in rats, contrasting with mice.
- Human exposure levels to EB and DEB are lower than in rats, and studies on BD-exposed humans show mixed results regarding gene mutations, with some reporting positive findings.
- Chromosome aberrations in humans are rare, with possible exceptions in lymphocytes of workers exposed to very high BD levels.
Conclusions:
- The genotoxicity of 1,3-butadiene is primarily mediated by its electrophilic metabolites, with DEB being the most potent.
- Species differences in DEB metabolism influence the observed mutagenicity and carcinogenicity of BD.
- While human exposure levels are low, understanding metabolite potency and abundance is crucial for assessing BD's overall genotoxicity risk.
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