A Prevalidation Study for Three-dimensional Cultured Human Skin Models as Slternatives to Skin Irritation testing

Iwao Sonoda11, Hajime Kojima2, Atsushi Sato2, Matsumi Terasawa3, Maki Goda4, Michimasa Hori5, Hiroko Okamoto6, Makoto Mizuno6, Noriyasu Imai6, Mai Takei6, Nobuyuki Uetake7, Misako Goto8, Rumi Kawabata9, Yoshifumi Sasaki10, Kaoru Ukawa11, Noriyasu Ozawa12, Tamie Suzuki13, Masahito Usami14, Tomoko Kasahara15, Kyoko Goto16, Hisashi Torishima17, Hidekazu akahashi18, Takuya Ishibashi18, Noriyuki Morikawa19, and Isao Yoshimura1
1 Tokyo Univ. of Science, 2 Nippon Menard Cosmetic, Co., Ltd., 3 IVY Cosmetic Co., Ltd.,
4 AJINOMOTO Co., Inc., 5 ICHIMARU PHARCOS Co., Ltd., 6 KOSE Corporation,
7 KOWA Co., Ltd., 8 KONICA Corporation, 9 TAIHO Pharmaceutical Co., Ltd.,
10 TANABE Seiyaku Co. Ltd., 11 Japan Bayer Agrochem K.K., 12 PIAS Corporation,
13 FANCL Corporation, 14 HOYU Co. Ltd., 15 POLA Substance Industries Inc.,
16 HOKKO Chemical Industry Co., Ltd., 17 KURABO Industries Ltd., 18 TOYOBO Co., Ltd.,
19 GUNZE Ltd.

Correspondence: Iwao Sonoda, Dept. of Management Science, Faculty of Engineering, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Fax: 03-5228-8350, Email: sonoda@ms.kagu.tus.ac.jp

Original paper :AATEX 8(3-4):91-106
Abstract
Various cytotoxicity assays using cultured cells or physico-chemical tests are available as an alternative to testing skin irritation potential of substances on human subjects. Most, however, are unsatisfactory, having led to the development of three-dimensional cultured human skin models (3D skin models) that are closer to human skin. This paper presents results of a prevalidation study carried out to obtain data for designing future validation studies, being conducted in Japan using three 3D skin models (EPI-100, TESTSKIN, and Vitrolife-Skin).
Five substances including two vehicles are processed using these 3D skin models under masking the name of substances. Skin irritation potential is evaluated by the scores of the time (ET50) with 50% damage on the 3D-skin model used. The observed result was compared with scores on human bodies and animals obtained in the Research Labs., Nippon Menard Cosmetic Co., Ltd. The feasibility of the tested 3D-skin models as alternatives was suggested through the experiment, although inter-laboratory variation was not neglected. The study protocol should be improved for future studies concerning, for example, the number of time points to be measured and the method to get reliable ET50 scores.
Five masked substances including two vehicles were considered, with skin irritation potential being evaluated using time-dependent ET50 scores compared to rabbit and human scores obtained by a commercial laboratory. Experimental results suggest that the proposed 3D skin models are feasible alternatives, although inter-laboratory variation was clearly apparent. In addition, future validation studies should incorporate improved protocols, e.g., stating specific times and methods such that reliable ET50 scores can be obtained.

Keywords: skin irritation potential, human skin model, cytotoxicity assay alternative method, cosmetic testing, validation study


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