Nicomenthyl Skin Penetration

Skin Penetration Study Protocol: this test method has been designed to provide information on absorption of a test substance applied to the surface of a skin sample separating the two chambers (a donor chamber and a receptor chamber) of a diffusion cell. In vivo viable human skin has been used. The skin has been shown to have the capability to metabolize some chemicals during percutaneous absorption. In this case, metabolites of the test chemical in the epidermis and under epidermis may be analyzed by appropriate methods. A quantity of 3000 µg of Nicomenthyl (in Caprylic Capric Triglyceride) is used as test substance and applied to the test system (HRE). This application should mimic a human exposure of 6000 µg/cm2. The temperature must be constant because it affects the passive diffusion of chemicals. The absorption of a test substance during a given time period (24h) is measured by HPLC analysis of the receptor fluid and the distribution of the test substance and its main metabolite (Niacin) in the test system and their absorption profiles with time are presented in appropriate graphic formats at 15 min, 30 min, 1h, 2h, 4h, 8h, 24 h after application.


A quantity of 3000 μg of Nicomenthyl was applied to a sample of HRE (in vitro Human Reconstructed Epidermis). A very high rate of penetration through the stratum corneum was observed, reaching an amount of 53.8% of the applied dose in only 30 minutes. The whole process of absorption and hydrolysis into its two components, Menthol and Niacin, gets practically completed in a period of 24 hours after application.


While Nicomenthyl penetrates through the skin barrier, it gets hydrolyzed into Menthol and Niacin (Vitamin B3). The Niacin so released gets immediately distributed both in the epidermis and under the epidermis.

HPLC analysis revealed a total amount of 254 μg of released Niacin having penetrated the skin barrier (from the initial 1413 μg contained in the 3000 μg applied dose of Nicomenthyl), i.e. a Niacin absorption rate of approx. 18% of the applied dose in 24 hours (= 0.75% per hour). These results are very significant, especially if compared to the absorption rate of the commonly used Niacinamide (another form of Vit. B3), which is only 11% of the applied dose in 120 hours (0.09% per hour); or to the absorption rate of pure Niacin itself, which is less than 1% of the applied dose in 120 hours (less than 0.008% per hour).*

The Journal of Investigative Dermatology – © 1970 The Williams & Wilkins Co.