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in vitro clastogenicity

Based on the outcome of guideline-compliant studies barium dichloride does not induce chromosome aberrations in mammalian cells, when tested up to toxic and/or precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9 mix).

Overall it can be concluded that barium dichloride does not induce chromosome aberrations in vitro in somatic mammalian cells. Therefore the conduct of in vivo clastogenicity experiments is not required.

in vitro gene mutation

Anonymous (1994)

The authors state that barium dichloride induces gene mutations in cultured mouse lymphoma cells (L5178Y) in the presence of S9 in a statistical significant manner. However, the mutation frequency increased from 32 per 106

cells in the control culture to a maximum of 59 per 106 cells at 1000µg/mL (with a RTG of 10%). Being a statistical significant increase in mutation frequency, the biological fignificance however is considered questionable, since the highest MF is still well below the value recommended by the IWGT (Moore et al., 2003; Moore et al., 2006; Moore et al., 2007) of 154 per 106 cells. Furthermore a comparison with historical data for the performing laboratory is not possible, since the data was not given in the study report.

 

Due to the questionable biological relevance, the statistical significant increase in mutation frequency in both barium dichloride cultures with metabolic activation is not considered as clear positive response. Therefore it was decided to repeat the whole experiment under clearly defined conditions, which a highly pure test item under guideline and GLP compliant conditions.

 

Lloyd (2010)

It is concluded that barium dichloride did not induce gene mutations in the TK locus of L5178Y mouse lymphoma cells when tested up to toxic and/or precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9 mix).

 

Overall it can be concluded that barium dichloride does not induce gene mutations in vitro in bacteria and somatic mammalian cells. Therefore the conduct of in vivo gene mutation experiments is not required.

 

 

References

Moore M et al. (2003)

Mouse lymphoma thimidine kinase gene mutation assay: International workshop on Genotoxicity tests workgroup report – Plymouth, UK 2002. Mutation Research (2003), 540, 127-140.

 

Moore M M, Honma M, Clements J, Bolcsfoldi G, Burlinson B et al. (2006)

Mouse lymphoma thymidine kinase gene mutation assay: follow up meeting of the International Workshop on Genotoxicity Testing – Aberdeen, Scotland, 2003 – Assay acceptance criteria, positive controls, and date evaluation. Environmental and Molecular Mutagenesis 2006, 47, 1-5.

 

Moore M M, Honma M, Clements J, Bolcsfoldi G, Burlinson B et al. (2007)

Mouse lymphoma thymidine kinase gene mutation assay: meeting of the International Workshop on Genotoxicity Testing, San Francisco, 2005, recommendations for 24-h treatment. Mutation Research 2007, 627, 36-40.

Justification for classification or non-classification

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation tests (TK assay) or in mammalian cell chromosome aberration tests, thus the classification criteria according to regulation (EC) 1272/2008 as germ cell mutagen are not met.

 

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