Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.

Summary

An IWGT subgroup conducted a systematized review of in vitro transcriptomic biomarkers for genotoxicity and identified five candidates, three of which (GENOMARK, TGx-DDI, MU2012) have defined contexts of use and validation. These panels improve specificity over standard assays by capturing stress response signatures and are progressing toward regulatory acceptance for cosmetics, drugs, and environmental chemicals.

Key Findings

• IWGT identified five in vitro transcriptomic biomarker candidates; three (GENOMARK, TGx-DDI, MU2012) have defined context of use and validation.
• Biomarkers address poor specificity of standard genotoxicity tests by leveraging transcriptomic stress response signatures.
• Challenges and progress toward regulatory acceptance were synthesized across pharmaceuticals, cosmetics, and environmental chemicals.

Clinical Implications

Improved specificity in genotoxicity screening can reduce false positives, streamline cosmetic ingredient safety assessments, and accelerate safer product development without animal testing.

Limitations

• Systematized but not a full PRISMA-compliant systematic review; potential publication bias
• Heterogeneity across platforms and chemical classes may limit direct comparability

Future Directions

Head-to-head benchmarking across panels, prospective ring trials, and integration into regulatory guidance to enable broader adoption in cosmetics safety assessment.