Ask a RIFM Scientist: How is fragrance safety evaluated?


In late 1964, A. L. van Ameringen, Board Chair of International Flavor and Fragrances, Inc. (IFF), sent a letter to seven leaders in the fragrance industry inviting them and their top technical staff to a meeting to discuss product safety.

Van Ameringen and his colleagues realized that pooling their resources together would have a more significant impact on ensuring the safe use of fragranced products than by continuing to do their own siloed research. Their historic meeting led to the nonprofit incorporation of the Research Institute for Fragrance Materials, Inc. (RIFM) in 1966.

For more than 50 years since then, RIFM has been at the forefront of the movement to ensure the safe use of fragrance ingredients. As science and our understanding of the ethical treatment of animals has evolved, RIFM has moved away from in vivo (animal) testing, pioneering the use of rigorous and now globally accepted animal-alternative methodologies and scientifically proven computer models.

RIFM’s Safety Assessment Manager, Danielle Botelho, PhD, oversees the Safety Assessment process and the team of scientists and post-docs who evaluate fragrances, helping to ensure consumers that they can safely enjoy their favorite fragranced products.

Q: In late 2014, RIFM published a fully-revised, peer-reviewed update to its criteria for evaluating the safety of fragrance materials, resulting in a new series of Safety Assessments. What scientific improvements led to this significant change?

The Criteria Document outlines the latest risk assessment methodologies, including alternatives to animal testing. We can better leverage our knowledge of the chemical similarity between fragrance materials. If we do not have data for a material of interest, but we know enough about a sufficiently similar one, we can bypass unnecessary testing and confidently assess the safety of the material of interest. This “read-across” strategy is a critical piece of our process.

The launch of the Creme RIFM Aggregate Exposure Model, which estimates a person’s total potential exposure to a fragrance material from all fragranced products, significantly improves exposure information. In turn, this enhanced exposure data helps us make fuller use of the threshold of toxicological concern (TTC), a method used to determine if the current level of exposure to a fragrance material is safe in the absence of any available studies.

RIFM’s use of read-across and TTC has saved over 450,000 animals.

Q: When RIFM started this refined series, how did it decide which materials to evaluate first?

RIFM has been writing about fragrance materials since the early 1970s, first as simple monographs, and then, in the early 2000s, as group summaries covering several materials in a single overview. (All of RIFM’s published research and assessments can be downloaded for free at

In 2013, RIFM realized the need for a new set of criteria that would take advantage of the latest science, including alternatives to animal testing. The Criteria Document shifted the focus from group summaries to assessments of individual (“discrete”) materials.

At first, RIFM started reevaluating materials with the highest volume of use, according to the International Fragrance Association’s (IFRA’s) Volume of Use survey. Because we focused on the volume of use, RIFM has now assessed and has been granted Expert Panel approval of Safety Assessments for more than 85% of the single component fragrance materials currently in use. (See below for more about the Expert Panel for Fragrance Safety.)

That’s a significant milestone, but the process wasn’t efficient in terms of the number of materials being evaluated. So, in 2016, RIFM pivoted to evaluating chemically similar materials at the same time, which resulted in an increase in output of 800% when comparing 2013-2015 to 2016­­-2019.

Q: How does RIFM evaluate the impact of fragrances on human health and the environment?

RIFM has a team of 16 scientists specializing in various areas of human health and environmental sciences. They come from biology, chemistry, engineering, and toxicology programs across the globe.

RIFM’s scientists work as a team to evaluate data and consumer exposure to determine conditions of safe use. We have the largest database for fragrance materials in the world. But we also make use of more than a dozen other database options to help ensure that we exhaust all available data before doing any testing—always prioritizing non-animal methods.

Q: How does RIFM ensure that its work is objective?

First, our safety evaluation criteria are based on rigorous, internationally accepted methodologies.

n addition, every Safety Assessment must be reviewed and approved by the Expert Panel for Fragrance Safety, an independent, international team of academic scientists with no ties to the fragrance industry. Once the Expert Panel has approved a Safety Assessment, RIFM submits it to a reputable scientific journal for a thorough peer-review before it will be accepted for publication.

The Expert Panel and independent, peer-review processes provide two layers of objectivity on top of RIFM’s science-based evaluations.

Q: When will RIFM’s work evaluating fragrance materials be complete?

Science is always evolving, and consumer use of products is continually changing. Because of this, RIFM must periodically reexamine the materials used by the industry.

Safety assessments are dynamic, “living” documents, and RIFM reevaluates materials on a rolling five-year basis to help ensure safe conditions of use.

Q: What’s next on RIFM’s safety evaluation horizon?

Complex mixtures are the materials of focus as we move into 2020 and beyond. We have been preparing new evaluation protocols since 2018 and are partnering with collaborators across the globe to integrate the latest science into our safety assessment process of complex mixtures.