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Forceps probing a bright flower held by a hand in a medical glove

Advancing the science to support the safe use of fragrances

12.15.20

The scientists who work at the Research Institute for Fragrance Materials (RIFM) have dedicated their careers to promoting human health and environmental safety.

Their primary commitment is to the RIFM Safety Assessment program, which follows the organization’s peer-reviewed 2015 Criteria Document to ensure that consumers can safely enjoy their favorite fragranced products.

RIFM’s Safety Assessment program is supported by research that enhances and expands the set of tools used to evaluate the safe use of fragrance ingredients.

This year has marked a watershed for RIFM’s Research program. RIFM’s scientists published five groundbreaking, peer-reviewed papers in 2020 that enhance our understanding of fragrance ingredients’ safety, providing insights and methodologies to help further avoid expensive, time-consuming, and unethical animal and human testing.

Clustering and Read-across

Organizing chemicals into structurally similar groups, also known as “clustering,” has helped RIFM scientists evaluate thousands of ingredients without testing them on animals.

RIFM Computational Chemist Mihir Date, PhD, and fellow scientists from RIFM and the Expert Panel for Fragrance Safety published a paper detailing RIFM’s use of chemical clustering and read-across (using data from one substance to help understand another, similar substance).

Published in Chemical Research in Toxicology.

The TTC

Consumers encounter most fragrance ingredients at extremely low exposure levels, even when adding up the total (or “aggregate”) of all fragranced products used.

The Threshold of Toxicological Concern, or TTC, is a level below which there is no appreciable risk of harm from a fragrance ingredient. The TTC provides an efficient, scientifically sound way to evaluate lower-exposure fragrance ingredients with limited toxicity data. Scientists compare these ingredients with other, similar ingredients for which there is a lot of data. RIFM’s use of the TTC has saved more than 265,000 animals.

RIFM Scientist Kaushal Joshi, PhD, and colleagues at RIFM and Procter & Gamble published a paper summarizing the fragrance material data that RIFM collected to add to the existing database supporting TTC values.

Published in Regulatory Toxicology and Pharmacology.

The DST

The Dermal Sensitization Threshold, or DST, borrows the TTC’s general principle when evaluating ingredients to ensure that they will not induce skin sensitization—the potential to cause an allergic skin reaction such as red, bumpy, or itchy skin in some people.

RIFM Vice President Anne Marie Api, PhD, and a group of international academics analyzed the use of DST in fragrance ingredients classified as “high potency,” which have a more significant potential for sensitization.

Published in Regulatory Toxicology and Pharmacology.

Confirming a safe-use level

When previous skin studies suggest that a fragrance ingredient has the potential to induce skin sensitization, RIFM must confirm a safe-use level with an ethical trial in humans.

The CNIH (short for “Confirmation of No Induction in Humans”) is a confirmatory human patch study that RIFM performs to confirm an already determined safe use level for fragrance ingredients.

CNIHs have been used by RIFM scientists for more than three decades to ethically confirm exposure levels below which there is no appreciable risk for skin sensitization to occur.

RIFM Scientist Mihwa Na, PhD, and a team of dermal experts outline what they discovered in analyzing the last 30 years of CNIH studies.

Published in Dermatitis.

Quantitative risk assessment

A quantitative risk assessment (QRA) is a science-based method of using large amounts of verifiable data to predict risk.

In 2008, RIFM Vice President Anne Marie Api, PhD, and an international team of skin experts published a paper defining a dermal sensitization QRA approach for fragrance ingredients. The QRA paper guided the scientists responsible for setting maximum concentration levels for fragrance ingredients in consumer products. These maximum concentration levels, in turn, informed the International Fragrance Association (IFRA) Standards for Safe Use.

This year, Dr. Api and an expanded team, including data scientists, updated the QRA paper with an improved method for establishing safe levels for potentially sensitizing fragrance ingredients.

Published in Regulatory Toxicology and Pharmacology.

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