The Continued Implementation of the Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients
Anne Marie Api—Research Institute for Fragrance Materials, Inc., Woodcliff Lake, NJ (www.rifm.org)
Matthias Vey—International Fragrance Association, Brussels, Belgium (www.ifraorg.org)
Significant developments have recently been incorporated in the way dermal sensitization risk assessments are conducted for fragrance ingredients. This, in turn, will have a substantial impact on the way that International Fragrance Association (IFRA) ingredient use restrictions based on dermal sensitization are implemented in the future. For more than a year an expert group, which included representatives from the fragrance and consumer products industries and Research Institute for Fragrance Materials, Inc. (RIFM), worked on refining this risk assessment methodology for fragrance ingredients. Details about the method for use with fragrance ingredients can be found on RIFM’s and IFRA’s Web sites (www.rifm.org/pub/publications.asp and www.ifraorg.org/news.asp).
This new methodology is a major improvement over the former approach because it specifically addresses the elements of exposure-based risk assessment that are unique to the induction of dermal sensitization, while being consistent with the principles of general toxicology risk assessment. The risk management strategies used in the past by IFRA for fragrance ingredients identified as allergens limited the use of the fragrance ingredient to the same concentration across all product types that involved skin contact. In the new QRA approach there are 10 different product categories for skin contact products. Category 11 is designated for non-skin or incidental skin contact products. Since exposure is a key element of category determination, this enables maintenance of relevant exposure and therefore safety, while providing greater flexibility to the perfumer because the limit is no longer the same across all skin contact applications. This means that, in some product applications, a higher fragrance ingredient concentration will be possible, while in others, a lower level may be specified, compared to what has been used in the past.
In brief, the key steps of the dermal sensitization QRA process for fragrance ingredients are:
- determination of benchmarks (no expected sensitization induction level, or NESIL);
- application of sensitization assessment factors (SAF) and
- calculation of consumer exposure (CEL) through product use.
Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the consumer exposure level (CEL). The ratio of the AEL to CEL must be favorable to support the safe use of the skin sensitizer. This ratio must be calculated for each fragrance ingredient identified as a potential skin sensitizer in each product type. (For more details, see the paper on the RIFM or IFRA websites written by the QRA Expert Group, Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, Technical Dossier, March 15, 2006, www.rifm.org/pub/publications.asp and www.ifraorg.org/news.asp).1). The principles and practical applications of this new methodology for fragrance ingredients continue to be presented at both fragrance and consumer product industry meetings as well as at toxicology and dermatology scientific meetings.2,3,4
Based on the RIFM Expert Panel’s recommendation, RIFM and IFRA have formally adopted the QRA approach, refined for fragrance ingredients identified as contact allergens, as the core strategy for primary prevention of dermal sensitization to these materials in consumer products. This methodology will be used to determine global fragrance industry product management practices (IFRA Standards) for potentially sensitizing fragrance ingredients, the first of which was implemented in May 2006 with the 40th Amendment to the IFRA Code of Practice. It contained the first four IFRA Standards based on the QRA and limited the use of the material for the 11 individual product categories. (For IFRA/RIFM information, see reference 5.)
The implementation of the QRA approach will continue with the publication of the 42nd Amendment to the IFRA Code of Practice. The 42nd Amendment will include all modifications to the existing Standards based on dermal sensitization for which there are adequate data to allow QRA review (approximately 20 Standards, covering about 30 materials). In addition, approximately 15 new IFRA Standards (covering about 20 materials) will be introduced, which cover most of the fragrance ingredients that require “allergen labeling” in Europe. As with previous Amendments, some of these new IFRA Standards restrict fragrance ingredients that can be found in other sources such as essential oils, so this needs to be taken into account.
The timing for implementation of this Amendment in existing formulae will be extended to 25 months due to the extensive number of Standards that are being revised. To view diagrams for regular timing for Amendments and timing for the 42nd Amendment only, click here.
QRA Implementation Workshop
RIFM and IFRA held a QRA Implementation Workshop for all (member and non-member) supplier and client companies on January 23, 2007. Due to the many changes anticipated with the 42nd Amendment, another workshop will be held on Monday, June 4, 2007. This workshop is being designed to provide continued guidance to both the supplier and client industries. As such, the workshop will once again be open to all member and non-members and will again be made available via webinar. More details will be provided in the coming weeks on the RIFM and IFRA Web sites.
- QRA Expert Group (Anne Marie Api, David A. Basketter, Peter A. Cadby , Marie-France Cano, Graham Ellis, G. Frank Gerberick, Peter Griem, Pauline M. McNamee, Cindy A. Ryan and Bob Safford), Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, Technical Dossier, revised June 22, 2006, www.rifm.org/pub/publications.asp and www.ifraorg.org/news.asp.
- AM Api, DA Basketter, PA Cadby, M-F Cano, G Ellis, GF Gerberick, P Griem, PM McNamee, CA Ryan and B Safford, Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, The Toxicologist, 90(S-1): 465 (2006).
- AM Api, Application of the Dermal Sensitization Quantitative Risk Assessment for Fragrance Ingredients—Practical Examples, European Society Contact Dermatitis, September 13, 2006, Berlin, Germany (2006).
- PM McNamee, Dermal Sensitization Quantitative Risk Assessment (QRA) For Fragrance Ingredients: What’s New? European Society Contact Dermatitis, September 13, 2006, Berlin, Germany (2006).
- IFRA/RIFM Informational Booklet, May 12, 2006, www.rifm.org/pub/publications.asp and www.ifraorg.org/news.asp.