Where is the fragrance industry with the QRA today?
First implemented by the fragrance industry in 2006, and since updated, the dermal sensitization Quantitative Risk Assessment (QRA) is considered an important step forward.
The QRA approach is considered by the industry as an important step forward in dermal sensitization risk assessment, and the method, first published in 2001 (Gerberick et al., Contact Dermatitis, 45:333-340) has been implemented by the fragrance industry since 2006. An update has been published in 2008 (Api et al., Regulatory Toxicology and Pharmacology, 52:3-23) and the QRA Expert Group* encourages further refinement to the QRA for fragrance ingredients. Some areas of improvement are considered below.
Improved exposure data (Hall, 2011) is being incorporated into the QRA methodology. In addition, RIFM has sponsored work to investigate the effects of aggregate dermal exposure. The outcome of this work is being accounted for in the methodology and we suggest that an open discussion be held on the validity of the QRA and on this initiative in particular.
A paper which specifically addresses the use of uncertainty factors in QRA for skin sensitization has been published (Felter, et al., Contact Dermatitis, 2003, 47:257-266). However it is acknowledged that further dialogue on SAFs would be appropriate. This would include better clarification of what the SAFs are applied to (e.g. not to clinically diseased skin).
A more detailed explanation of AELs and how they are applied should be provided. There also is a need for more details on the pragmatic approach and a review of aspects of having high calculated values in (mainly) rinse-off products.
While occupational exposures to consumer products can be an important source of exposure they are not considered in the current QRA. This mainly stems from a lack of adequate exposure data. Furthermore the QRA methodology does not cover aromatherapy (neither workers nor customers). These currently not reflected exposures remain a potential area of research.
Diagnostic patch test data from dermatology clinics are not used in the primary determination of safe use levels based on induction. This is because these data are a measure of elicitation of allergic contact dermatitis, not induction. Nevertheless, the diagnostic patch test data provide feedback on whether thresholds of used based on the QRA has been correctly established (see Task II.2).
A review of retrospective data for three fragrance ingredients has been published (Api et al., 2010). Retrospective review of other fragrance ingredients and other non-fragrance ingredients should also be considered.
Thus, clinical results from the dermatology community (including targeted studies) and company post-market surveillance data should be used to evaluate the effectiveness of QRA-based interventions.
The best way to address the validity of the QRA methodology and the possibilities of further refinement would be to organize an in-depth dialogue between experts. We recommend that a specific workshop be held on the QRA methodology.
The best way to address the validity of the QRA methodology and the possibilities of further refinement would be to organize an in-depth dialogue between experts. We recommend that a specific workshop be held on the QRA methodology.
Footnote
* The QRA Expert Group is a RIFM Task Force of ten toxicologists from the fragrance and the downstream users industry. This group worked on the adaptation of the QRA methodology to the Fragrance Industry and continues to watch the outcome of the QRA implementation in view to improve the model.