The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date

Area of Science:

• Toxicology
• Dermatology
• Cosmetic Science

Background:

• High rates of misleading positives in in vitro genotoxicity tests pose challenges for cosmetic safety assessments.
• Existing mammalian cell assays require optimization for improved predictive capacity.
• Need for reliable in vitro methods that mimic dermal exposure conditions for cosmetic products.

Purpose of the Study:

• To address misleading positives in in vitro genotoxicity testing.
• To optimize existing mammalian cell assays and develop new models for genotoxicity assessment.
• To validate the use of 3D reconstructed skin models for evaluating cosmetic ingredients.

Main Methods:

• Optimization of the in vitro micronucleus assay with relevant cells and sensitive toxicity measures.
• Development and validation of human reconstructed skin (RS) models combined with micronucleus (MN) and Comet assays.
• Investigation of enzyme capacities in human skin and RS models to assess metabolic profiles.

Main Results:

• Optimized micronucleus assay demonstrated dramatically improved predictive capacity.
• 3D RS models showed good inter- and intra-laboratory reproducibility for MN and Comet assays.
• RS models exhibited metabolic capacity comparable to native human skin, supporting their use for dermal exposure testing.

Conclusions:

• The program has improved the predictivity of initial genotoxicity test batteries.
• 3D reconstructed skin models provide strong support for their use as follow-up tests in genotoxic hazard assessment.
• These advancements offer a more reliable approach for evaluating cosmetic ingredients, especially in the absence of in vivo data.