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  4. New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk
 
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2015
Journal Article
Title

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk

Abstract
The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk+/- or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal.
Author(s)
Kirkland, David
Brock, Tom
Haddouk, Hasnaà
Hargeaves, Victoria
Lloyd, Melvyn
Mc Garry, Sarah
Proudlock, Raymond
Sarlang, Séverine
Sewald, Katherina  
Sire, Guillaume
Sokolowski, Andrea
Ziemann, Christina  
Journal
Regulatory toxicology and pharmacology  
Open Access
File(s)
Download (645.55 KB)
Rights
CC BY-ND 4.0: Creative Commons Attribution-NoDerivatives
DOI
10.24406/publica-r-240839
10.1016/j.yrtph.2015.07.016
Language
English
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Keyword(s)
  • genotoxicity

  • overall assessment

  • cobalt compounds

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