IDEA - International Dialogue for the Evaluation of Allergens

Dermal Sensitization QRA

The Dermal Sensitization QRA (Quantitative Risk Assessment) is used to evaluate the risk of induction of skin sensitization resulting from the exposure to allergens via consumer products. This methodology was adapted to fragrance allergens and its main features are published in the peer-reviewed journal 'Regulatory Toxicology and Pharmacology'. This article can be downloaded from the RIFM website.

 

This methodology intends to prevent individuals from getting sensitized to fragrance allergens by deriving maximum use levels for each of them for 11 consumer product categories.

Allergic Contact Dermatitis (ACD) is a skin disease implying the immune system and happening in two steps: an induction phase, which primes and sensitizes the immune system for an allergic response, and an elicitation phase, in which this response is triggered. Elicitation occurs after new exposures to the skin sensitizer having caused the skin sensitization.

It is now generally accepted in the scientific community that both the sensitization and the elicitation phases are triggered by a threshold mechanism. Preventing induction automatically prevents the issue of sensitization. For this reason, safe use levels preventing induction are established for each allergen via an appropriate risk assessment methodology. 

The QRA methodology is based on many parameters but, before all, on the skin sensitizer potency. The potency determination is the usual result of the hazard assessment. Skin sensitisers potency can range from very weak to extreme but the majority of fragrance allergens are weak sensitizers. All available scientific studies on the skin sensitizer potency are combined using the Weight of Evidence (WoE) approach to give a quantitative value: the NESIL or “No Expected Sensitization Induction Level).

Then, the NESIL is translated in terms of real risk for the consumer by taking several factors into account. Together, these factors make the Sensitization Assessment Factor (SAF). For the time being, these factors are:

  • The inter-individual susceptibility because some people are more sensitive than others to skin sensitizers. It can be due to the genetic predisposition, age or skin condition.
  • The matrix effect because some matrices are more aggressive than others (e.g. presence of irritants).
  • The use pattern because the area where the skin sensitizer is applied has an importance in the sensitization process (e.g. a deodorant applied to an occlusive and sensitive area is more problematic than a shampoo).

The QRA methodology blends the NESIL and the SAF to define a maximum use level for each fragrance allergen and product type in order to avoid induction. This maximum use level has to be compared with the real exposure to this allergen on the marketplace. Risk management measures need to be taken each time the exposure observed on the marketplace goes beyond the maximum use level.