Pioneering non-animal testing for photoallergy in fragrances: A Q&A with RIFM's Gretchen Ritacco
As the demand for safer and more sustainable beauty products grows, the cosmetics and personal care industry is increasingly looking for innovative solutions that minimize the need for animal testing while ensuring consumer safety. One of the key areas of focus is the evaluation of photoallergy potential in fragrance ingredients.
Earlier this year, Gretchen Ritacco, the Research Institute for Fragrance Materials (RIFM) Principal Scientist for Dermatotoxicology, presented critical research in collaboration with the Institute for In Vitro Sciences (IIVS) at the 2024 Biennial Meeting of the American Society for Photobiology. The presentation highlighted new assays developed to detect photoallergens and shared promising results on known photoallergens.
As the field of photobiology proliferates, Ritacco's work represents a significant step toward advancing non-animal testing alternatives, with the potential to transform regulatory compliance and safety assessments for the cosmetics and personal care industries.
In this CosmeticsDesign Q&A, Ritacco sheds light on the collaborative efforts with the Institute for In Vitro Sciences (IIVS), challenges in this field, and how these advancements are shaping the future of safety testing in the fragrance industry.
CDU: Can you elaborate on the significance of developing non-animal tests to evaluate the photoallergy potential of fragrances? What are the key challenges these tests aim to address?
Gretchen Ritacco (GR): For more than a decade, RIFM has focused its significant Safety Assessment and Research investments on pioneering rigorous and globally accepted animal-alternative methodologies to eliminate the reliance on animal testing while ensuring consumers continue to enjoy fragranced products safely. RIFM does not perform animal testing for any of its human health endpoints, including photoirritation/photoallergy.
But we need more options when evaluating a material for its photoallergenic potential. We can determine whether a material absorbs in the UV/Vis range using the OECD test guideline 101, and we can address photoirritation, but we still lack in vitro assays specific for photoallergy. That lack is the issue this research aims to tackle.
One of the challenges to this research has been that it is a relatively small field. For years, there were not many labs seemingly interested in working on photoallergy. There are also only a few known photoallergenic materials to build the assays and confirm that they work as designed.
In addition, in vitro systems often struggle to survive irradiation. There have been plenty of additional challenges along the way, and the pandemic occurred just as we were getting started on this research, which obviously slowed things down.
CDU: Why was the collaboration with the Institute for In Vitro Sciences (IIVS) important for this research, and what role did they play in developing the new assays?
GR: The collaboration with the Institute for In Vitro Sciences (IIVS) was crucial for this research. Together with RIFM and Shiseido, we brought newly developed assays for photoallergy in-house at IIVS. The scientists at Shiseido played a significant role in training and transferring the technology to IIVS.
These in vitro assays, originally designed for skin sensitization and with OECD guidelines, have been modified to include UV exposure. This modification allows us to use them to identify potential photoallergens.
RIFM has long partnered with IIVS to expand their assay offerings to tackle critical questions concerning photosafety. IIVS already offer the photo-Direct Peptide Reactivity Assay (photo-DPRA) and are working towards providing the photo-Keratinosens™ and photo-human Cell Line Activation Test (photo-h-CLAT).
CDU: What are the most significant findings from your study on known photoallergens that you presented at the American Society for Photobiology’s Biennial Meeting?
GR: When we tested known photoallergens in these new assays for photoallergy, the assays worked, and they were able to detect the photoallergens. This tells us that the assays are doing what they were designed to do, which is an important initial step in our research.
CDU: How might the feedback from experts at the Biennial Meeting influence the future direction of your research?
GR: In this relatively small field, we value and are open to any feedback from experts. Their insights and suggestions can significantly contribute to the advancement of our research.
One of the biggest challenges we face with the development of new photoallergy assays is that there are not a lot of known or “reference” photoallergens. Reference photoallergens are necessary to tell us if the new assays are detecting what they were designed to detect. We have a small pool of reference photoallergens that we have been using as positive controls for these new assays.
Feedback from other experts in the field might include materials to incorporate into our list of reference photoallergens to provide further proof of concept for the new assays. We are currently working on a manuscript on a weight-of-evidence approach for classifying photoallergens in which we will identify reference materials with compelling evidence for photoallergenicity.
CDU: How do you see the adoption of these new approach methodologies (NAMs) for photoallergy testing impacting the cosmetics and personal care product industries, particularly regarding regulatory compliance and safety assessments?
GR: The adoption of these NAMs for photoallergy testing could significantly impact the cosmetics and personal care product industries. If we can demonstrate that these assays work as designed and can provide us with information on the potential for a material to cause photoallergy, two important outcomes can be expected.
First, once the Expert Panel approves them, we can test any fragrance ingredient that has yet to be fully evaluated for photoallergy. This information would be included in RIFM’s fragrance ingredient safety assessments.
Secondly, the assays could become more widely available at contract labs, gain regulatory acceptance, and be used by others in the cosmetics and personal care products industries to address photosafety.
CDU: In the absence of OECD-guidelined in vitro assays for photoallergy, how do you think your research could contribute to the development of standardized testing protocols in the future?
GR: RIFM has pioneered, refined, and substantiated animal-alternative methodologies for over a decade through our research program while simultaneously evaluating all materials in use by the fragrance industry. Our safety assessments reflect and apply the latest data and objective test methodologies.
Because we make all of our peer-reviewed safety assessments and research available open access, scientists worldwide have easy access to information on reliable methods they can apply in real-time to advance consumer safety. All of RIFM’s work is reviewed and guided by the Expert Panel for Fragrance Safety.
They provide independent, unbiased scientific support for the safe use of fragrance materials. Down the road, this could lead to new OECD guidelines.
CDU: What are the next steps for RIFM and IIVS in advancing non-animal testing methods for photoallergenicity? Are there any upcoming studies or collaborations that you are particularly excited about?
GR: The future for RIFM and IIVS in advancing non-animal testing methods for photoallergenicity is promising. We continue to collaborate on the photo-DPRA, photo-Keratinosens, and photo-h-CLAT assays. We have recently signed agreements to test even more reference chemicals, which is a significant step forward.
We are also working with SenzaGen, a lab in Sweden, on modifying their Genomic Allergen Rapid Detection (GARD) dose-response assay with UV exposure for use in detecting photoallergens. Like the work with IIVS and Shiseido, this is an important collaboration based on an assay developed for skin sensitization. That research is also moving forward with testing more reference photoallergens.
Once we have full confidence in the assays and the support and approval of the Expert Panel for Fragrance Safety, we will start to test some of the fragrance materials we have not fully evaluated for photoallergy. We are particularly excited about these upcoming studies and collaborations and believe they hold great potential for the future of our research.
CDU: How can the cosmetics and personal care industry leverage your findings to improve product safety and consumer trust, particularly with the growing demand for non-animal testing alternatives?
GR: Fragrance safety stakeholders can easily access our findings and those that leverage our approaches can assess photosafety with the most objective, reliable science available. RIFM continues to integrate the latest, evolving methodologies while scanning for all available, reliable data (including exposure and the latest consumer habits & practices), so the world can enjoy fragrance safely.
CDU: Given that photobiology is a relatively small field, what other research areas do you believe hold the most potential for advancing the science of photoallergy and related skin sensitivities?
GR: We have already borrowed a lot from the field of skin sensitization since photoallergy is analogous to skin sensitization, but UV exposure is required for the reaction to occur. Most of the methods we are researching started as assays for skin sensitization. RIFM also leverages the collective expertise of our staff chemists and the Expert Panel for Fragrance Safety who have published extensively on the RIFM read-across approach.
This work has been invaluable in confirming structurally similar “read-across materials” when the materials we are evaluating lack photosafety data. This toxicologically sound strategy helps save time and money on unnecessary testing.
CDU: Given these advancements, what advice would you give to companies in the cosmetics and personal care industry looking to stay ahead of the curve in terms of safety testing and regulatory compliance?
GR: To avoid any potential photosafety issues, it makes sense to consider photosafety in both raw materials and finished products.
To this end, I recommend making sure you have ruled out photoirritation. Photoallergy is more of a challenge, but we are making progress on that front, and I hope we will soon have in vitro methods for photoallergy. Your commitment to safety and consumer trust is crucial, and our research is aimed at supporting and enhancing this commitment.
