A Step-by-Step Approach for Assessing Human Skin Irritation Without Animal Testing for Quasi-Drugs and Cosmetic Products

Abstract

Introduction: Animal tests of cosmetic ingredients and products have been banned in the EU since 2013. However, in Japan, the application of new quasi-drugs requires the generation of 24-hour data on primary and cumulative skin irritation by animal testing. Such data are unreliable because an ingredient predicted as nonirritating after short exposure (4 hours), based on the Organization for Economic Co-operation and Development (OECD) test guidelines (TG)404, may cause irritation after a longer application period in human skin irritation tests. With insufficient data to draw conclusions about the irritation potential of an ingredient, there remains a high probability of skin irritation occurrence after extended exposure to the ingredient. Materials and Methods: This study assessed whether the skin irritation caused by quasi-drugs and cosmetic products can be evaluated in a step-by-step manner. Results: A workflow was developed considering several key steps such as the component characteristics based on physicochemical properties or the ingredient category based on existing information from animal tests and human patch test results, and its utility was assessed using the reconstructed human epidermis (RhE) test (OECD TG439), animal testing, the human patch test, and the human cumulative skin irritation test. Conclusion: The RhE test and the aforementioned human skin tests can be employed to evaluate test substances that cause weak or nonskin irritation categorized as “harmless ingredients”—thereby avoiding animal testing.