Feeling a bit itchy? Skin sensitisation from fragrance ingredients in cosmetics, personal care products and household goods is relatively common and causes considerable concern for fragrance manufacturers and regulators. The QRA2 model, developed by the International Fragrance Association as part of the International Dialogue for the Evaluation of Allergens (IDEA) Project, is designed to derive an acceptable exposure level for such fragrance allergens, i.e. a concentration below which induction of sensitisation is unlikely to occur. The SCCS has evaluated the model and concluded that it could be useful for the risk assessment of fragrance allergens and other cosmetic ingredients, subject to clarification on certain issues.

As with all risk assessments, the methodology requires a point of departure for derivation of the acceptable exposure level. In this case, the no expected sensitisation induction level (NESIL), broadly equivalent to the no observed adverse effect level (NOAEL) that might be used in a systemic toxicity risk assessment, is derived using a weight-of-evidence approach, from existing animal and human studies. The SCCS expressed concerns over the ethics of commissioning new human repeated insult patch tests (HRIPTs) for derivation of the NESIL. It also questioned the lack of an inter-species modifying factor when using an EC3 value from a mouse LLNA. In a sector where new animal testing is prohibited, the authors of QRA2 themselves identified a potential future issue with NESIL derivation using only in vitro and/or in silico data.

The use of uncertainty or modifying factors is a cornerstone of risk assessment. However, QRA2 appears to have a wide and confusing array of such sensitisation assessment factors (SAFs) and their application is not entirely clear. There is no justification given for the use of an inter-individual SAF of 10 (the same as is used in other industry sectors) when the evidence suggests greater human variability for susceptibility to induction of skin sensitisation, or for the product-specific SAF which ranges from 0.3 to 3 depending on the extent of dermal penetration of the substance. When considering the impact of skin condition, SAFs of 1, 3 or 10 have been proposed for 18 specific body sites – the SCCS calls for an explanation as to why these sites each need to be considered separately.

As far as exposure is concerned, we humans typically use more than one product on the same area of skin (facewash, toner, serum and moisturiser anyone?) – or we may use multiple products containing the same fragrance allergen on different areas of our body. The methodology does not adequately explain how consumer exposure to fragrance allergens is determined, particularly in the case of aggregate exposures such as those described above (surely not shampoo and conditioner?).

QRA2 could well serve as the basis for the risk assessment of other substances causing skin sensitisation, a notoriously complex toxicity endpoint. Bibra awaits with interest the response of QRA2’s authors to the SCCS preliminary opinion, and further output from the IDEA project.

References

IDEA (2016). International Dialogue for the Evaluation of Allergens. Final report on the QRA2 skin sensitisation quantitative risk assessment for fragrance ingredients. September 30, 2016. http://www.ideaproject.info/uploads/Modules/Documents/qra2-dossier-final–september-2016.pdf

SCCS (2017). Scientific Committee on Consumer Safety. Preliminary opinion on skin sensitisation quantitative risk assessment for fragrance ingredients (QRA2). SCCS/1589/17. https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_211.pdf

 

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