Critical Evaluation of Methods for the Identification of Aneugens

The HESI Global Genetic Toxicology Technical Committee (GTTC) has published a critical new review in Environmental and Molecular Mutagenesis titled “Critical Evaluation of Methods for the Identification of Aneugens.”  This publication provides much-needed clarity on using NAMs to evaluate aneugenic potential, helping to advance safer chemicals, medicines, and regulatory practices.

The Issue
Chemicals that interfere with chromosome number, known as aneugens, can lead to severe health consequences, including developmental disorders and cancer. Regulatory frameworks across pharmaceutical, industrial, and consumer sectors require accurate evaluation of such genotoxic risks. However, distinguishing aneugenicity from other types of chromosome damage remains challenging.

Why it Matters
Accurately identifying how a chemical causes genetic damage (its mode of action) is critical for making informed human health risk assessments and designing appropriate follow-up studies. Without this, potentially harmful exposures may be mischaracterized, potentially delaying development or overlooking risks.

The Problem
Microscopy-based techniques like FISH or CREST staining have widely been used to identify chromosomal damage mechanisms, but are low-throughput, and limited in mechanistic insight. This makes them difficult to apply consistently across regulatory and industrial settings.

The Solution
To address these limitations, the HESI Global Genetic Toxicology Technical Committee  conducted a comprehensive review and SWOT analysis of legacy methods (FISH and CREST) alongside emerging New Approach Methodologies (NAMs), including high-content imaging and flow cytometry. The team applied these tools to in vitro studies using well-characterized reference aneugens (colchicine, taxol, AMG900) and clastogens (mitomycin C, MMS).

The Benefit
This work illustrates how NAMs can improve the accuracy and efficiency of genetic toxicology assessments. This review provides a roadmap for integrating more advanced, tools into safety science, supporting HESI Global’s mission to create science-based solutions for a safer, more sustainable world.

Read the open-access article:

Critical Evaluation of Methods for the Identification of Aneugens. Sun et al., 2025. Environmental and Molecular Mutagenesis. https://doi.org/10.1002/em.70023