ADME / Tox >> In Vitro Toxicity >> Genotoxicity

Determine your drug’s genotoxic potential early in discovery

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Approval and registration of drugs requires a comprehensive assessment of their genotoxic potential. Genotoxicity testing is an integral component of regulatory toxicity evaluation in most countries. Since no single test is capable of detecting all relevant genotoxic end-points, a battery of in vitro and in vivo tests for genotoxicity is recommended by regulatory agencies. The recommended standard test battery includes in vitro tests for gene mutation in bacteria (Ames test) and in mammalian cells (mouse lymphoma assay) or an in vitro test for chromosomal damage in mammalian cells (in vitro micronucleus test or in vitro metaphase chromosomal aberration assay). Additionally, an in vivo test for chromosomal damage (in vivo micronucleus or in vivo chromosomal aberration assay) is required by regulatory agencies as part of an IND application.

Recently, assessment of genotoxicity testing has evolved towards earlier stages of drug discovery in order to identify genotoxic liabilities at a time when changing lead series will have a relatively low impact on a project's timeline and cost. Assays such as the Ames fluctuation test and the in vitro micronucleus assay (for the assessment of the in vitro chromosomal aberration) offered by Eurofins are routinely used for screening compounds.

Advantages of Eurofins' Genotoxicity Assays:

  • Ames fluctuation test and in vitro micronucleus assays are offered to meet ICH S2(R1) recommendations
  • Assays require small amount of compound and provide rapid turnaround time (10 business days)
  • The Ames fluctuation test utilizes 4 Salmonella typhimurium tester strains (TA98, TA100, TA1535 and TA1537) to detect both frameshifts and base-pair substitutions
    • Testing can be performed with and without metabolic activation by rat liver S9 fraction
  • Bacterial cytotoxicity assays are conducted concurrently with Ames test to confirm the negative Ames results
  • The in vitro micronucleus assay uses automated scoring by High Content Analysis (HCA) which provides objective and consistent data when compared with manual scoring.

 

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