A remarkable year for the science supporting fragrance safety
This year, scientists at the Research Institute for Fragrance Materials (RIFM) worked relentlessly to ensure that everyone can safely enjoy their favorite fragranced products. As a result, RIFM moved the science supporting fragrance safety assessment forward considerably, completing a record-breaking 11 research papers that provide insights and methodologies to expand our understanding and further avoid expensive, time-consuming, and unethical animal and human testing.
We’ll provide more details for many of these publications in the new year. Meanwhile, here is an overview of what RIFM accomplished in 2021.
An NCS “Criteria Document”
Natural Complex Substances (NCS) are fragrance ingredients extracted from plants and are complex mixtures of many components. The safety assessment of NCS is similar to and just as robust as the stepwise process that RIFM uses to assess discrete fragrance ingredients. The same endpoints are evaluated via the latest science and animal-testing alternatives to ensure the ethical, safe use of fragranced products.
RIFM plans to submit its first NCS Safety Assessments guided by this NCS criteria document in the coming weeks. Watch out for a free Elsevier-hosted webinar covering this paper in early February.
The RIFM approach to evaluating Natural Complex Substances (NCS) was published in Food and Chemical Toxicology. (An open-source version will be available via the Fragrance Safety Resource Center soon.)
A Criteria Document for Photoirritation
Photoirritation is a skin reaction that occurs when an exogenous (not something your body made) substance is applied to the skin and exposed to ultraviolet (UV) rays. In photoirritation, the affected area of the skin may resemble an exaggerated sunburn. These one-time effects go away over time and occur in anyone given enough of the substance combined with UV light.
For a substance to be photoirritating, it must absorb UV rays. However, of the more than 1800 ingredients with no photoirritation data, some 94% do not absorb UV rays, meaning they pose no concern for photoirritation. This paper, which provides an update for photoirritation to the original Criteria Document, looks at case studies of 108 ingredients that do absorb, outlining RIFM’s tiered approach to assessing their safe use with no reliance on animal testing.
The Use of Alternative Test Methods in a Tiered Testing Approach to Address Photoirritation Potential of Fragrance Materials has been peer-reviewed and accepted for publication in Regulatory Toxicology and Pharmacology.
Animal-Alternative Assays and Screening Tools for Genotoxicity—and a Rare Case Study
RIFM’s Genotoxicity team has focused on verifying two animal alternatives for assessing a fragrance ingredient’s potential to compromise DNA, the carrier of genetic information.
When in vitro (in Petri dish or test-tube) studies show results for DNA mutations or chromosome breaks and alterations, an animal follow-up study was once necessary to confirm these results. RIFM, however, can ensure the results with:
- the EpiDerm 3D Reconstructed Skin Micronucleus assay; and
- an ethical chicken egg model that follows similar guidelines to confirmation animal studies.
RIFM’s Genotoxicity Team and colleagues recently published a paper verifying the use of the EpiDerm 3D Skin assay in Oxford Academic’s peer-reviewed journal Mutagenesis. Their report confirming the use of the chicken egg model is being completed with a planned submission to a peer-reviewed journal in January 2022.
In rare cases where existing methods cannot verify a material’s genetic safety, RIFM publishes its findings in the peer-reviewed literature. That material will then be banned for use as a fragrance ingredient. For example, this was recently the case with mintlactone; the findings were published in Food and Chemical Toxicology.
The Genotoxicity Team completed two other research papers this year. The first evaluates the effectiveness of the BlueScreen HC, a mammalian cell-based assay for measuring genotoxicity. RIFM uses the assay as a screening tool to prioritize fragrance ingredients for higher-tier testing. This report compared the BlueScreen results of 371 ingredients with in vitro and historical in vivo (animal) data and found that the BlueScreen tool did not produce false-negative results. The paper is currently in the revision stage at Mutagenesis, with peer-reviewed publication expected to follow.
The final research paper shows how the Toxtree assay can provide RIFM scientists with information needed to identify the most appropriate animal alternative follow-up assay for those testing positive in BlueScreen, such as the 3D skin assay or the chicken egg model, thus eliminating the need to run both tests. RIFM’s Genotoxicity Team will submit this paper for peer-reviewed publication by the end of this year.
A Criteria Document and Supporting Evidence for Skin Sensitization—Plus Two Collaborations
RIFM’s Skin Team has published an update for Skin Sensitization to the Criteria Document. The paper details how RIFM derives the NESIL, short for “no expected sensitization induction level,” using all available data. The NESIL is used to help identify maximum acceptable concentrations of an ingredient in fragranced products, which in turn inform the International Fragrance Association (IFRA) Standards. (Published in Food and Chemical Toxicology.)
RIFM’s Skin Team also completed research showing that using all available data (e.g., human, historical animal, Petri dish, test tube, and computer modeling) provides a weight of evidence for the most robust understanding of an ingredient’s potency. Potency refers to the amount of a substance required to initiate an allergic skin reaction in a previously unsensitized person and is critical to deriving the NESIL. This paper has been accepted for publication in the American Contact Dermatitis Society’s journal Dermatitis.
RIFM’s innovative, science-based animal alternative methods in this area anticipated the new OECD Guideline 497: Defined Approaches on Skin Sensitization. In a collaborative paper, RIFM, along with L’Oréal and Charles River Laboratories, report on the results of using the U-SENS assay, which performs as well as an earlier assay included in OECD Guideline 497, the human Cell Line Activation Test, or h-CLAT. RIFM anticipates that the U-SENS assay will be added to the OECD Guideline as one of the “me too” assays. This paper has been peer-reviewed and accepted for publication by Elsevier’s Toxicology In Vitro.
Finally, RIFM collaborated with Procter & Gamble (P&G) on a report on using the animal-alternative SENS-IS assay to determine the sensitization potential for fragrance ingredients. SENS-IS uses the reconstructed human skin model to determine hazard and potency of potential skin sensitizers. RIFM and P&G compared SENS-IS results to the weight of evidence (see above). They found that SENS-IS provides a useful approximation of skin potency to help identify ingredients for further testing. This paper was recently submitted to Elsevier’s Regulatory Toxicology and Pharmacology.
Congratulations to all of RIFM’s scientists on this most productive of years.