RESEARCH INSTITUTE FOR FRAGRANCE MATERIALS

Ask a RIFM Scientist: What is potency, and what does it tell us?


 


7/9/20
Among the natural and synthetic substances that scientists have identified as potential skin sensitizers, some are intrinsically more potent than others.

Skin sensitization refers to a substance’s potential to cause an allergic skin reaction (such as red, bumpy, or itchy skin) in some people. (Read more here.)

When assessing the safe use of a potentially sensitizing fragrance ingredient, RIFM’s skin sensitization team looks at both the ingredient’s potency and how much consumers may be exposed to the ingredient through fragranced products.

Isabelle Lee, PhD, joined RIFM as a Postdoctoral Researcher in January 2020. She aids the skin sensitization team in conducting safety assessments and research projects.

Q: What is potency, and why is it important to understand it?

A: Potency refers to the amount of a chemical that is required to initiate an allergic skin reaction in a previously unsensitized person. We refer to that very first skin reaction as “induction,” and our goal is to prevent that from ever occurring.

It is essential to understand potency because it informs the threshold level of chemical exposure below which skin sensitization will not occur in someone who was not previously sensitized. The more potent a chemical is, the less is needed to cause an induction in skin sensitization.

Scientists categorize the potency of skin sensitizers according to their skin sensitization potential. There are four categories: weak, moderate, strong, and extreme. The majority of sensitizers fall into the “weak” category.

Q: Why is potency so critical to assess the safety of a potential sensitizing ingredient?

Scientists have identified the majority of those fragrance ingredients that are sensitizers to be weak sensitizers. But, the no-effect level for a weak sensitizer may be 3000 µg/cm2 or 30,000 µg/cm2. So, it is essential to understand the specific potency for each weak sensitizer.

Once a fragrance ingredient is determined to be a skin sensitizer, its potency level informs the setting of a no-effect level, which RIFM uses to determine the maximum acceptable concentrations for ingredients. RIFM assigns maximum acceptable concentrations for use in specific products, based on how consumers use each product. The International Fragrance Association (IFRA) refers to these concentrations when they create their Standards.

Q: How does RIFM determine the potency of a potential skin sensitizing fragrance ingredient?

A: Historically, scientists have determined the skin sensitization induction potency for fragrance ingredients through animal tests with available OECD guidelines, such as the local lymph node assay (LLNA).

However, with the rise of ethical awareness and as improved technologies became available, RIFM pioneered the process of researching and validating new non-animal testing methods to be used to categorize sensitizers by potency. RIFM has not performed skin sensitization studies on animals in more than seven years.

Q: How does the determination of potency inform RIFM’s current Safety Assessments?

A: RIFM’s safety assessment for skin sensitization follows the general framework for toxicological evaluation.

First, we must identify a chemical’s potential hazard. Many elements of our lives present a hazard. For example, water is potentially hazardous, as drinking it in large quantities can disrupt the balance of electrolytes, leading to water intoxication, an often fatal condition.

But hazard is only half of the story. Next, we must determine whether the hazard poses an actual health risk, given specific conditions. We know, for instance, that drinking eight glasses of water in a day poses no risk to a person’s health.
Hazard identification for skin sensitization is a straightforward process and does not present a significant challenge because we have developed methods to do this.

Risk characterization for skin sensitization is more complicated. Characterizing a risk requires an understanding of chemical potency, which informs us of the potential of a chemical exposure to result in the induction of skin sensitization.

Q: What drew you to RIFM’s Postdoctoral Research Program?

A: I acquired my PhD in Pharmacology from the University of Pennsylvania, where I defended my dissertation on the role of polycyclic aromatic hydrocarbon metabolites in endometrial cancer.

In addition to the PhD program, I trained in Environmental Health Sciences, where I became interested in pursuing research on non-animal alternatives for chemical testing.

I was drawn to RIFM’s Postdoctoral Research Program because of RIFM’s pioneering innovation in the use of new in silico and in vitro methods in the assessment of the safety of fragrance ingredients, promoting the reduction of animal testing without compromising human health.