Mutagenicity and Genotoxicity | OECD 487

The In vitro Mammalian Cell Micronucleus Test (MN Test, OECD TG 487) is a cornerstone of most regulatory genotoxicity test strategies. It is widely used to identify substances that cause chromosomal damage by identifying both clastogenic effects (chromosome breakage) and aneugenic effects (chromosome number alterations).

To further investigate the mode of action, centromere staining using Fluorescent In Situ Hybridization (FISH) probes is available. This allows differentiation between clastogenic and aneugenic mechanisms as required for REACH when the number of micronuclei is increased in the MN test.

Specific adaptations of this guideline are needed for the testing of nanomaterials. Demonstrating cellular uptake and confirming effective exposure are critical for scientifically robust results. The exposition should ideally be within a stable dispersion.

Test principle

The in vitro micronucleus test evaluates the formation of micronuclei in interphase cells. These micronuclei may originate from:

·         Acentric chromosome fragments (lacking a centromere), or

·         Whole chromosomes that fail to segregate properly during anaphase

The assay assesses a substance’s potential to induce genetic damage in cells that have undergone at least one cell division cycle during or after exposure.

Test scope

The first experiment will be carried out using short exposure with and without metabolic activation. If the result is negative or inconclusive, a modified second experiment should be performed: extended exposure without metabolic activation or short exposure and increased S9 concentration (with metabolic activation). Formulation analysis is possible.

Test system

TK6 CRL8015 TM (human lymphoblast cell line isolated from spleen)

Endpoint

The genotoxic potential of a substance is determined by comparing the micronucleus rate of the individual test item concentrations to that of a negative control (solvent only). In case of a positive result (genotoxic) a subsequent FISH analysis can then be used to distinguish between the mode of actions involved (clastogenic or aneugenic).

 

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