December 6, 2010

Discovery of reduced hair coloring sensory irritation
using carbonate ions by Mandom-Identifying the mechanism of “alkali” sensory irritation for the firsttime in the worldMandom Corporation (Head Office: Osaka, President Executive Officer: Motonobu Nishimura, hereafter“Mandom”) has been developing products offering “superior feel and function” and that are of “reliable and safequality.” In particular, we have been developing a technique to offer customers with “reliable” products while
completely assuring gentler effects on the skin.
As part of this research, Mandom has identified the mechanism of sensory irritation caused by “alkali” jointlywith Professor Makoto Tominaga of the National Institutes of Natural Sciences. Furthermore, using this mechanism
we discovered the possibility of reducing sensory irritation from hair coloring by using carbonate ions.
At Mandom, we are adopting this technique to reduce sensory irritation for “GATSBY Bubble Bleach HairColor” and “LUCIDO-L Bubble Hair Color,” which will likely be available this spring.
Mandom is attempting to further explore this technique to improve the product “reliability” from a consumerperspective.
Furthermore, we presented the results of this study at the “The 26th Congress of the International Federation ofSocieties of Cosmetic Chemists (IFSCC)” held from September 20 to 23, 2010 in Argentina.
1. “Alkali” are the cause of sensory irritation from using hair color
Many people experience “tingling” and “stinging” sensory irritation on their scalps when using hair coloring.
Mandom discovered that it is often caused by “alkali” (ingredients to increase pH) that are normally added to haircoloring (excluding manicures, etc.). “Alkali” are needed, both for color removal by breakdown of melanin in thehair, and coloring through dye polymerization, which are essential for hair coloring. Previously, addition ofexcessive “alkali” was considered to augment the dyeing effect, but it also simultaneously increases the sensory
irritation of the scalp. In addition, the mechanism of sensory irritation from “alkali” is unknown, and therefore,
there has been no definitive approach to reducing it.
* “Alkali” are medically known to cause pain, including the “tingling” pain from illnesses as the blood alkalizes
due to hyperventilation (hyperventilation alkalosis) and nasal mucosal pain caused by ammonia gas.

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-1-2. Identifying the mechanism of “alkali” sensory irritation for the first time in the world
Mandom has focused on “TRP channels”. Recent research confirms that these are receptors of chemical
irritants and temperature. Exploiting these receptors, Mandom has developed an alternative technique forevaluating sensory irritation. Mandom is pursuing various studies to reduce the slightest unpleasant “sensoryirritation” caused in rare instances by “safe” cosmetics that do not trigger inflammation. Among the TRPchannels, we identified that TRPA1, a receptor for spicy ingredients in wasabi and pepper, is activated by“alkali” (Fig. 1). Furthermore, the mode of action is identical to the activation of TRPA1 due to intracellular
alkalization by “alkali” (especially ammonia) (Fig. 2).
3. Discovery of carbonate ions for reducing sensory irritation from hair coloring
Mandom hypothesized that sensory irritation from hair coloring could be reduced by preventing intracellularalkalization. Therefore, the quest for ingredients capable of inhibiting intracellular alkalization due to “alkali”
commenced. We discovered that “carbonate ions” are able to inhibit intracellular alkalization (Fig. 3). So, we first,
confirmed the ability of “carbonate ions” to reduce sensory irritation using a sensory irritation evaluation method
for hair coloring involving sensitive subjects recruited by Mandom. Based on the results, we confirmed that sensory
irritation caused by hair coloring could be reduced by adding “carbonate ions” (Fig. 4).

-2-4. Application of carbonate ion-based sensory irritation reduction to new spring 2011 products
At Mandom, we are applying this sensory irritation reducing technique to “GATSBY Bubble Bleach HairColor” and “LUCIDO-L Bubble Hair Color,” which will be available by spring 2011. We shall continue refining
this technique so many more consumers are able to enjoy hair coloring without experiencing unpleasant “tingling”
or “stinging” sensory irritation.

Low←TRPA1 activation→HighLow←TRP channel activation→High<Reference material>

TRP channels involved in sensory irritation

Neutral ← Intracellular pH → Alkaline

Ammonia
Ammonia+carbonate ions

Low←Alkali concentration→HighFig. 3．Effect of carbonate ions on intracellularalkalization

Fig. 2. Effect of intracellular alkali on TRPA1
Low←Sensory irritation→HighNeutral←Intracellular pH→Alkaline

Fig. 1. Effect of alkali on TRP channels

Low←Carbonate ions concentration→HighFig. 4．Suggested sensory irritation withcarbonate ions-3-<Mechanism of sensory irritation>
Thanks to the recent progress in life sciences that has
led to the identification of “irritation sensors” in nerve cells
in the skin. These sensors detect chemical substances andtemperature, convert the sensory signal to electrical signal,
which is key to sensory irritation (Fig. 4) cascade.
“Tingling” and “stinging” irritation partly resembles
temperature perception. It has been reported that irritatingsensations and temperature perception are perceived via thesame sensor, namely the “TRP channels” (Fig. 5).

Temperature atwhich painful heat

Chili pepper Garlic

Warm tocool temperatures
Mint
Temperature atwhich painful cold
is feltWasabi Cinnamon(Sodium ions)(Calcium ions)
Outer cell side

Inner cell side
Sensory nerve cell

Irritation sensor
Nerve cell excitation

Fig. 4. Irritation sensors in sensory nerves

TRP channels have recently gained attention as
receptors present in the skin and sensory nerves
functioning as sensors. Typical examples include
TRPV1, the receptor for capsaicin (main ingredient inchili pepper) and TRPM8, the receptor for menthol(main ingredient in mint). Many ingredients added tocosmetics generally cause sensory irritation andactivate the TRP channels. Examples include citric acid,lactic acid, alcohols and camphor.

GarlicFig. 5 TRP channels receiving temperature and irritation-4-