The validation and regulatory acceptance of alternative methods in Japan

Except for the genotoxicity test, there are two regulatory guidelines in Japan for in vitro toxicity studies. One of them is a cytotoxicity test for the safety evaluation of extracts from plastic devices for medical use. The other is an in vitro endotoxin test (the Limulus test). These are included in the Japanese Pharmacopoeia. Japan also accepts data obtained from these tests conducted according to OECD guidelines. On the other hand, the Ministry of Health and Welfare (MHW) indicated in 1996 that they would accept alternatives to the Draize eye irritation test for safety evaluation of cosmetics if the method were appropriate. Therefore, the MHW/Japan Cosmetic Industry Association validation group conducted validation studies on alternative methods and indicated that the results of several cytotoxicity tests correlated very well with those of Draize scores obtained from rabbit tests. Based on the results, draft guidelines to evaluate the eye irritation potential of cosmetic ingredients were prepared and submitted to the MHW 1999, in which in vitro methods were incorporated. Validation requires a lot of resources and time. Therefore, we recently constructed an evaluation scheme for alternative methods with the support of the Ministry. This was based on the research, on published manuscripts, and on validation reports. We intended to clarify the performance of the method with its limitations. Without having this information, both regulators and industry persons would make big mistakes in evaluating the results of alternative methods. As a first trial of the project, research on the in vitro phototoxicity test was conducted.