The 4 QRA Steps

The QRA approach for fragrance ingredients follows the same four steps involved in general toxicology risk assessment:

1. Hazard identification
2. Dose-response assessment or hazard quantification
3. Exposure assessment
4. Risk characterization 

1. Hazard Identification

This step consists of determining the potential (hazard) of a fragrance material to induce sensitization. It is performed using:

• pre-clinical studies, e.g. Guinea-Pig Test and Local Lymph Node Assay (LLNA)
• existing human data (historical)
• a structure-based predictive approach.

2. Dose–Response Assessment

This step consists of establishing the relationship between dose (level of exposure) and the probability that an adverse effect will occur. This involves:

• the determination of No-Expected Sensitization Induction Levels (NESILs), based on the Weight of Evidence (WoE) expressed in dose/unit area, using scientifically robust data and a set of established guidelines
• the calculation of a Sensitization Assessment Factor (SAF) to take into account inter-individual variability, vehicle/product matrix impact and use considerations. The SAF is determined by the extrapolation from controlled experimental situations to real-life exposure scenarios.

3. Exposure Assessment

This step aims to determine the amount of a fragrance ingredient (dose) that individuals will receive. It uses habits and practices data as well as established human parameters data.

• Consumer Exposure (CE) data in different product categories is used to calculate how consumers are exposed to a material in terms of amount, duration and frequency
• Consumer Exposure is expressed in common unit of exposure (µg/cm²)
• Calculation for daily exposure to the fragrance ingredient in the product type gives the Consumer Exposure Level (CEL) in µg/cm²/day.

4. Risk Characterization

This step consists in placing an identified hazard in the context of human experience. More specifically, it consists in establishing Acceptable Exposure Levels (AELs) to fragrance ingredients (dermal sensitizers) in specific real-life consumer product types.

• The NESIL & SAF resulting from step 2 are used to calculate an Acceptable Exposure Level (AEL), expressed in µg/cm².
  AEL=NESIL/SAF
• To be acceptable, the CEL (Consumer Exposure Level) needs to be lower than the AEL (Acceptable Exposure Level).
  CEL<AEL