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Genotoxicity Focus group

This Focus group highlights the importance of addressing the genotoxicity of nanomaterials and possible consequences for human health. The group, established in 2011, focuses on mechanisms of genotoxicity, particularly nano-specific mechanisms, on the use of existing genotoxicity assays, and on the development of high-throughput genotoxicity screening tests for nanogenotoxicity. It will address basic problems of genotoxicity testing such as which assays, models and genotoxicity endpoints are the most appropriate for nanotoxicology; comparison of in vitro and in vivo genotoxicity; inclusion of nano-related positive controls in genotoxicity testing, handling of and treatment with nanomaterials in terms  of reproducibility; relevant dose; exposure route;  QA and GLP; and impact on genotoxicity. An important question is: what is the impact of interactions of nanomaterials with biological systems (through uptake, oxidative stress, inflammation  or other mechanisms) on DNAdamage and repair, mutagenicity and clastogenicity?  The group also aims to harmonise genotoxicity testing protocols for nanotoxicology.

 

The questions we are addressing: 

  • Do nanomaterials interact with  - nucleus, chromosomes,DNA,DNArepair - directly or indirectly?
  • What are possible mechanisms and are there nano-related mechanisms of genotoxicity?
  • What is the impact of nanomaterial uptake, oxidative stress or inflammation on genotoxicity?
  • Do existing tests need modification or adaptation for testing nanomaterials, and what are the most crucial aspects to address?
  • Which assays are the most appropriate and why?
  • And which biological models should we choose?
  • Does in vitro genotoxicity of ENMs correlate with in vivo genotoxicity?
  • What is the value of new assays and high-throughput tests?Which testing scheme (strategy) for the assessment of genotoxicity of ENM should we choose?

 

Time line          : 2012

Coordinated by :Maria Dusinska

Members list    :   Mischeline Kirsch-Volder, Hannu Norpa, Andrew Collins, Alena Kazimirova, Alok Dhawan, Vicky Stone