The RIFM approach to evaluating Natural Complex Substances (NCS)

Area of Science:

• Fragrance Material Safety
• Toxicology
• Risk Assessment

Background:

• The Research Institute for Fragrance Materials (RIFM) has a 55-year history of evaluating fragrance material safety.
• Natural Complex Substances (NCS) require safety assessments comparable to discrete fragrance materials, evaluating the same toxicological endpoints.
• Advances in risk assessment for mixtures and toxicology necessitate updated methodologies.

Purpose of the Study:

• To establish a comprehensive safety assessment process for Natural Complex Substances (NCS) used as fragrance ingredients.
• To adapt existing safety evaluation frameworks for the unique challenges posed by NCS.
• To ensure the safe use of NCS in consumer fragrance products.

Main Methods:

• A tiered, 4-step risk assessment process is employed for each endpoint, prioritizing data evaluation and computational methods over new testing.
• Step 1: Evaluate existing data on NCS. Step 2: Assess applicability of the Threshold of Toxicological Concern (TTC). Step 3: Determine if component-based risk assessment is feasible. Step 4: Identify data generation needs.
• In silico tools were utilized to analyze NCS similarities across 81 plant families based on plant part, processing, and composition, addressing data gaps.

Main Results:

• The RIFM Aggregate Exposure Model, utilizing data for over 900 fragrance NCS, identified dermal exposure as the primary human exposure route.
• A significant portion (over one-third) of evaluated NCS fall below the most conservative Threshold of Toxicological Concern (TTC) limits.
• The implemented process effectively addresses data gaps and provides a robust framework for NCS safety evaluation.

Conclusions:

• The developed tiered approach provides a scientifically sound and efficient method for the safety assessment of NCS in fragrances.
• The findings support the safe use of a substantial number of NCS, with many demonstrating exposure levels well below established safety thresholds.
• This systematic evaluation ensures consumer safety while optimizing resource utilization in fragrance ingredient assessment.