Overview

The micronucleus test (MNT) is used to determine if a compound is genotoxic by evaluating the presence of micronuclei. Micronuclei may contain chromosome fragments produced from DNA breakage (clastogens) or whole chromosomes produced by disruption of the mitotic apparatus (aneugens).

Screening and Regulatory Support

  • Male and/or female rats or mice are treated with the test compound at three dose levels, usually two or three times at 24-hour intervals.
  • Approximately 24 hours after the last dose, bone marrow or peripheral blood is collected to determine the frequency of micronucleated polychromatic erythrocytes (MN-PCEs) or micronucleated reticulocytes (MN-RETs), respectively.
  • A positive outcome is characterized by a statistically significant, dose-dependent increase in MN-PCEs or MN-RETs that exceeds historical control limits.
  • Can be combined with standard toxicology tests, the comet assay and the Pig-a assay.
  • Administration routes include: oral, intravenous, infusion and inhalation

When to Perform

  • Screening
    • Abbreviated formats available or can be added to non-GLP tolerability studies
  • IND-enabling
    • As part of the ICH S2(R1) standard battery (Option 1 or 2)
  • REACH requirement
    • To follow up a positive result in any of the Annex VII or VIII genotoxicity tests