October 9, 2007

Evaluation of sensory irritation using irritant
receptors: novel method development in the cosmetics
industry by Mandom to develop gentler skin products- Envisioning cosmetics free of uncomfortable “tingling” and “stinging”-

The Mandom Corporation (Head Office: Osaka, President Executive Officer: Motonobu Nishimura, hereafter“Mandom”) has
focused its research on establishing an “evaluation technique for elucidating pleasantness and unpleasantness” to develop“comfortable” products for customers. As part of this research, Mandom has developed an evaluation method for unpleasant“tingling” and “stinging” sensations felt on rare occasions when using cosmetics. We hope to utilize these findings at Mandom toevaluate a wide variety of products.
Furthermore, we have presented the results of this study at the “6th International Conference on Alternatives to Animal Testing(Tokyo)” held in Japan on August 25.
1. Background of the study
In recent years, consumers have become increasingly conscious of safety and security, based on the fact that 60-90% of all
women report having a sensitive skin. Despite recent improvements in manufacturing, and fewer cosmetics resulting in “tingling,”“stinging” or other unpleasant sensations during use, there are customers that cease using cosmetics due to sensory irritations. Inaddition, there are increasing number of cases where in consumers can no longer use cosmetics they have long used without problems
due to sudden irritation from seasonal changes or physical conditions. Thus, sensory irritation is a major factor not only for a
comfortable use of cosmetics by consumers, but also in deciding whether to use or not. However, the mechanism of sensory irritation
is often not understood, and thus meaningful solutions are not proposed. Evaluation of sensory irritation has mostly involved stinging
tests of human subjects. Accuracy of human-based evaluations may be improved depending on the test sites and application methods,
but nevertheless, there are drawbacks, as inconsistencies are common. Also, it is difficult to increase the number of tests within ashort period of time. In order to develop a technique for reducing unpleasant sensory irritations, we first require a method for
precisely evaluating sensory irritation that allows for numerous tests to be conducted.
Therefore, at Mandom, we have conducted a study to develop an evaluation method for sensory irritation that does not use
human skin.
* Stinging test: a method for evaluating sensory irritation in people by applying a sample of the cosmetic to human skin.

Contact

mandom corp.
Public Relations Div.
mail: press@mandom.co.jp

URL: https://www.mandom.co.jp/en/

Please contact us in Japanese or English.

-1-Heat!
Cold!
Pain!

2. Perception of “pain” and “heat”
How do people sense “pain” and “heat”? People perceiveBacknoxious stimuli and temperature on the surface of the body. This

Brain

Electricalsignals aretransmitted

information is transmitted to the brain in the form of electricalsignals, and we perceive feelings of “pain” or “heat” (Fig. 1) In thesuperficial layer of the skin, chemical substances that cause

Cold temperature
stimulation ICE

Spinalchord

temperature and noxious stimuli are converted to electrical signalsFoot

present in the sensory nerves (Fig. 2).

Hot temperature stimulation

Fig. 1 Transmission of “pain” information
The mechanism by which people sense noxious stimuli andtemperature was not identified several decades ago. Human irritant
receptors and temperature reception are very closely related. Thiswas discovered based on receptors that were activated byPain irritation

Sodium ions
Calcium ionsTemperature
irritation

ICE

Outside cellstimulation from capsaicin, the alkaloid in chili pepper. It is also
activated by high temperature that causes pain. Amongst these, we Sensory nerve cell Inside cell
have chosen to focus on a group of membrane proteins called “TRP

Sodium ions
Calcium ions

(Transient Receptor Potential) channels,” which play a major role in
the perception of noxious stimuli and temperature in humans

Nerve cell
excitation(Fig. 3).
* Noxious stimuli: A stimulation caused by irritants from outside

Fig. 2 Irritant receptor (receptor)

the body.
3. Evaluation utilizing irritant receptors
TRP channels have recently been in the spotlight asa receptor for capsaicin (the alkaloid in chili pepper),and TRPM8, a receptor for menthol (the alkaloid inCapsaicin

Mentholsensory receptors in the skin and sensory nerves. TRPV1,WarmColdHotmint), are typical representatives.
In general, many of the ingredients added tocosmetics that cause sensory irritation activate the TRPchannels. Examples of these include preservatives such as
parabens, citric acid, lactic acid, alcohols and camphor.

Fig. 3 Temperature and irritation-sensing TRP channels

Based on these facts, we spent several years working on
establishing how to evaluate irritation using TRP channels. This had led to the first discovery in the cosmetics industry of a method
for evaluating irritation based on these irritant receptors. This method involves transfected cultured cells to express the irritantreceptors. These cells were then treated with irritants and calcium-specific fluorescent indicators were used to measure the changes incalcium concentration. By adopting the so-called “calcium imaging” technique, elevated calcium levels could be observed with highsensitivity as fluorescence intensity increased when the receptors were activated by compounds assessed for irritation. In other words,
substances that cause unpleasant “tingling” and “stinging” sensations could be detected with high accuracy.

-2-By continuing this research, we at Mandom hope to assess ingredients that may cause unpleasant “tingling” and “stinging”
sensations, which are a nuisance to many women. By seeking substances that may suppress these unpleasant sensations, we hope toensure comfortable women’s cosmetics are developed. In addition, we intend to use this technique to assess several marketableproducts, including hair coloring products that have slight irritation issues, and deodorants with long-lasting comfortable coolness.
We will attempt to thoroughly explore what “comfort” means to consumers, and determine how to further improve.
END-3-