Next-Generation Risk Assessment for cosmetic ingredients: a critical evaluation of published case studies

Area of Science:

• Toxicology
• Risk Assessment
• Cosmetic Science

Background:

• Animal testing for cosmetic safety is under increasing regulatory and scientific pressure.
• Next Generation Risk Assessment (NGRA) provides a human-centric framework utilizing new approach methodologies (NAMs).

Purpose of the Study:

• To critically evaluate the current state of NGRA in cosmetic safety assessments.
• To analyze case studies demonstrating NGRA's application across various toxicological endpoints.

Main Methods:

• Review of 9 published case studies involving 7 chemicals.
• Analysis of NGRA components: physiologically based kinetic (PBK) modeling, adverse outcome pathways (AOPs), integrated approaches to testing and assessment (IATA), and threshold of toxicological concern (TTC).
• Evaluation of defined approaches for skin sensitization and other endpoints.

Main Results:

• NGRA successfully identified safe concentrations for cosmetic ingredients, meeting regulatory safety margins.
• Defined approaches for skin sensitization and eye irritation have achieved regulatory acceptance.
• Significant gaps remain in validated NGRA frameworks for complex systemic toxicity endpoints.

Conclusions:

• NGRA demonstrates potential as a robust, ethical alternative to animal testing in cosmetic safety.
• Advancements require integrating metabolically competent models, AI, multi-organ micro-physiological systems, and standardized interpretation frameworks.
• A roadmap is provided for strengthening NGRA for comprehensive human health risk assessment.