WORK PLAN TASK II: DEFINITION AND CHARACTERIZATION OF ALLERGENS OF SPECIFIC CONCERN

The need is to agree on criteria for the identification of a (fragrance) allergen, which would define how to identify a ‘significant risk to the general population’.

Industry, the dermatological community, and regulators will work together to find a common ground and understanding on how to integrate clinical, cosmetovigilance and exposure data into the risk assessment in order to produce an accurate definition of “allergens of specific concern”. For instance, different levels of concern may be defined:

• Magnitude of the issue (low, medium or high percentage of population effected)
• Categories of allergens (all sensitizers, rare allergens, common allergens, allergens of (very) high concern, etc.)
• Sources and levels of exposure

In this respect there is a need to address questions related to the above definitions such as what defines a substance for which a risk assessment technique such as the QRA (based on avoidance of induction) is considered sufficient versus what defines an allergen for which other more restrictive measures need to be considered necessary.

Several areas of the risk assessment process require further refinement and understanding to allow their integration into a common methodology.

This need is particularly true for the exploitation of data that underline the definitions of fragrance allergens and allergens of specific concerns:

Use of toxicological data

This generally addresses primary prevention by attempting to identify safe exposure levels, which avoid the induction of skin sensitization. The QRA approach is clearly defined and published and is the basis of the existing IFRA Ingredient Standards on sensitization. However, there are still areas for further research and potential improvement (e.g. consideration of aggregate exposure). This is part of the fourth task.

Use of clinical data

Data from dermatology clinics is at the forefront of the identification of substances that cause allergy in the general population. However, dermatologists are not routinely included in the discussion on risk assessment. In addition to the interpretation of data, including dermatologists in active consideration of approaches to risk assessment will provide for a collaborative approach to establishing safe use conditions. The following aspects need to be considered in incorporating correctly use clinical data in the risk assessment process:

• Determination of contact allergy via the use of the patch test and whether there is a need for refinement to this tool (e.g. Nosbaum et al, 2009).
• Differentiation of cases with likely induction of sensitisation by the ingredient from cases with likely cross-reaction in elicitation (with allergy induced by a different chemical).
• The relationship between patch test exposure conditions and real life exposure (e.g. Maibach et al.) and clinical relevance of a positive patch test response (e.g. Ale and Maibach, 2010; DeGroot 1999, EDEN study data)
• Consideration of a scientific study to investigate the clinical relevance of positive patch tests.
• Definition of levels of concern: A clear definition is required to identify levels of concern of allergens. For instance, this definition may be based on an absolute number or percentage of patients within dermatological clinics reacting to a substance, number of clinically relevant cases per year, percentage of general population with (clinically relevant) reactions, etc. It might further be worthwhile to discuss cases of sensitization in relation to the marketed amount of an ingredient and use levels or more sophisticated stochastic analyses like allergy incidence in predicted exposed subpopulations.
• Potential role of alternative techniques to patch testing (like immunologic systems).
• Potential role of sample provision to dermatologists to facilitate diagnosis (is the system sufficiently effective?).

Use of Cosmetovigilance data

Cosmetovigilance data is an important source of information that is mostly held within consumer product companies, but can be used to identify emerging issues or substances of concern. The availability and quality of this data needs to be further explored to understand the potential usefulness of such data within this process. Consumer product companies could consider sharing data perhaps through a third party (to protect confidentiality), to enable a broad on-going use of sensitization incidence information to drive prioritization and decision making.

Discussion is needed on reliable protocols/measures to determine those thresholds and how far elicitation thresholds could be a relevant and reliable model for use in risk assessment. One focus should be comparing thresholds from ingredients with different potency, particularly weak sensitizers, the category that contains the majority of fragrance sensitizers.

The Research Institute for Fragrance Materials (RIFM)* is actively engaged in an elicitation threshold study for Eugenol, which could further inform these discussions. Insights from the already initiated Repeated Open Application Test (ROAT) with Oakmoss (containing atranol and chloroatranol) could also prove helpful.

We recommend that the appropriate use of elicitation thresholds for risk assessment be discussed and protocols/measures be agreed to determine them. The organization of a workshop of experts seems to be the best option to address the questions outlined above.