A Vision for the Future: How NAMs will refine our understanding of respiratory safety
Because fragrances are all about appealing to the nose, there has long been a general misunderstanding about human exposure to them. Many may assume that the most significant exposure to fragrance ingredients is inhaling them, but this isn’t the case.
As this New York Times article points out, most fragrance-producing substances have an enormous aromatic impact, even in insignificant amounts. For example, writing about vanillin, the main component of vanilla extract, the Times author writes that “its odor detection threshold is probably around 0.1 or 0.2 micrograms per cubic meter … That means that one or two oil tankers full of vanillin could conceivably be used as an air freshener powerful enough to give the entire Earth a slight scent of vanilla.”
The Research Institute for Fragrance Materials, Inc. (RIFM) is committed to building universal acceptance and trust in the safe use of fragrance materials through applied science and research. The potential for local respiratory toxicity is one of the critical areas of human health evaluated in every RIFM Safety Assessment.
Because odor detection thresholds for fragrance ingredients are so low, evaluating the safety of an ingredient can often be done using the concept of exposure-based waiving. Exposure-based waiving involves comparing the chronic inhalation exposure values for the fragrance material of interest with its respective Threshold for Toxicological Concern (TTC) limit, the limit below which no concern for safety is expected to exist. About 99% of the fragrance ingredients in current use fall below the most conservative TTC limit. As such, exposure-based waiving is an essential and effective animal alternative for the safety evaluation of inhalation exposure to fragrances. To help bolster and enhance the data supporting the inhalation TTC limits, RIFM is working with the Fraunhofer Institute, the US Environmental Protection Agency, Proctor & Gamble, and Cosmetics Europe.
Due to the lack of standard and validated non-animal tests for local respiratory effects and respiratory sensitization, RIFM has favored using existing data or exposure-based waiving over generating new data. Meanwhile, RIFM is researching animal-alternative New Approach Methodologies (NAMs) to address this critical human health endpoint.
RIFM continues to partner with Rutgers University and the Institute for In Vitro Sciences (IIVS) to differentiate between respiratory irritants, respiratory sensitizers, and skin sensitizers using human precision-cut lung slices. (A respiratory irritant, such as ammonia, may cause one-time symptoms like sneezing or coughing. On the other hand, a respiratory sensitizer can lead to an immune-system hypersensitivity of the airways following repeated or high enough levels of inhalation of the substance. There are no known respiratory sensitizers among fragrance ingredients.)
With the same objective, RIFM is collaborating with Dr. Arno Gutleb (Invitrolize SARL), whose newly established in vitro (non-animal) co-culture model has shown promising data for differentiating respiratory irritants from respiratory sensitizers.
More recently, RIFM partnered with Charles River Laboratories, IIVS, and the Fraunhofer Institute for Toxicology and Experimental Medicine to evaluate three different human tissueculture models for local respiratory effects from inhalation exposure to compounds with complex physical and chemical properties.
Finally, RIFM and the Monell Chemical Senses Center are collaborating on updating the odor detection and irritation thresholds for various fragrance ingredients to refine our understanding of how little of an ingredient needs to be included in a fragranced product to work its magic.
As Senior Scientist Nikaeta Sadekar, PhD, explains: “Fragrances are extremely personal. Everyone has their favorite, which is not necessarily the same as others. But despite these differences, underlying human biology is the same, and that’s why RIFM is working on building NAMs in these collaborations using human tissue cultures for ensuring human health safety for fragrance use.”
Read more: If I can smell it, is it safe?