In Vitro Irritation Testing of Alcohol-based Hand Rubs Using the Three-dimensional (3D) Human Skin Model

Abstract

[Background] The selection of alcohol-based hand sanitizers that cause minimal skin irritation is essential for the prevention of dryness and other skin problems in healthcare professionals. We used a three-dimensional (3D) skin model to perform skin irritation testing and to compare the results among seven alcohol-based hand sanitizers (class 3 OTC pharmaceuticals).

[Methods] The tests were conducted based on the OECD test guidelines (TG439). Cell viability was determined to be less than 50%, and IL-8 expression rates were determined to be irritating if they were a higher percentage than those of the negative controls. Ethanol concentrations were 78.89 vol% for reagent 1, 72 vol% for reagents 2 and 3, 76.9-81.4 vol% for reagents 4 and 5, and 83 vol% for reagents 6 and 7. Reagents 1-5 were ethanol-only, alcohol-based skin sanitizers, whereas reagents 6 and 7 were 0.2 w/v% chlorhexidine gluconate (CHG) -containing skin sanitizers containing alcohol. Reagents 1-3 had a pH range of 6.0-9.0, reagents 4 and 5 had a pH range of 2.6-4.0, and reagent 7 had a pH range of 5.5-7.0. The pH of reagent 6 was not disclosed.

[Results] The mean cell viability was 88%, 110%, and 79% for the ethanol-only formulations of reagents 1-3, and 68% and 61% for the two low-pH formulations of reagents 4 and 5.

The mean cell viability was 2.1% and 1.8% for the two formulations with 0.2 w/v% CHG, comprising reagents 6 and 7, and was determined, therefore, to be irritative.

Increased IL-8 expression was observed with both the low-pH formulations of reagents 4 and 5 (183% and 141%) and with reagent 6 (118%), one of the two 0.2 w/v% CHG-containing formulations.

[Conclusions] Skin irritation testing using a 3D skin model showed that ethanol-only, alcohol-based skin sanitizers were the least irritative to the skin.