Genetic Toxicology Studies - Study Design of Mammalian Bone Marrow Chromosomal Aberration Test (OECD 475)
Mammalian Bone Marrow Chromosomal Aberration Test (OECD 475) with you. Here’s a comprehensive overview of the test design, aiming to address various aspects:
Objectives:
- Detect structural chromosomal aberrations (breaks, gaps, exchanges) induced by a test substance in bone marrow cells of rodents.
- Assess the dose-response relationship for the observed aberrations.
- Classify the substance according to its potential to cause chromosomal damage and contribute to genotoxicity.
Test System:
- Animals (typically rodents like rats or mice) are exposed to the test substance at various doses, either through oral gavage, intraperitoneal injection, or inhalation.
- Exposure durations can range from single doses to multiple doses over several days.
- Bone marrow is extracted from animals at specific time points after exposure (usually during the dividing phase of cells).
Chromosome Preparation and Analysis:
- Extracted bone marrow cells are treated with a metaphase-arresting agent to capture dividing cells.
- Chromosomes are stained and visualized under a microscope.
- A defined number of cells (typically 100 per dose level) are analyzed for the presence and type of chromosomal aberrations.
Endpoints:
- Frequency of cells with chromosomal aberrations at each dose level.
- Types of aberrations observed (e.g., breaks, gaps, exchanges, translocations).
- Mitotic index (measure of cell division) to assess cytotoxicity.
- Clastogenic index (ratio of cells with aberrations to control cells) for dose-response evaluation.
- Classification of the substance based on OECD 475 criteria (e.g., clastogenic, non-clastogenic).
Benefits:
- Sensitive in detecting chromosomal aberrations.
- Provides information on direct damage to chromosomes in mammalian cells.
- Standardized and internationally accepted method.
- Relatively rapid and cost-effective compared to some other in vivo tests.
Limitations:
- Requires animal use, raising ethical concerns.
- Cannot detect all types of genetic damage (e.g., point mutations).
- May be affected by species and strain differences.
Additional Resources
- OECD Test Guideline 475: https://www.oecd.org/chemicalsafety/testing/50108781.pdf
- Mammalian Bone Marrow Chromosomal Aberration Test (OECD 475): https://www.nucro-technics.com/services/genetic-toxicology/genetic-toxicology-screening-tests/
- Test No. 475: Mammalian Bone Marrow Chromosome Aberration Test: https://www.oecd-ilibrary.org/environment/test-no-475-mammalian-bone-marrow-chromosomal-aberration-test_9789264264786-en
