Journal of Oral Tissue Engineering

ORIGINAL ARTICLE
Skin Sensitization Study by a New Qualitative Structure-toxicity Relationships (QSTR) Approach: K-step Yard Sampling (KY) Methods

Kazuhiro SATO1, Tomohiro UMEMURA1, Taro TAMURA1, Yukinori KUSAKA1, Kohji AOYAMA2, Atsushi UEDA3, Kohichi HARADA4, Keiko MINAMOTO3, Takemi OTSUKI5, Kunihiko YAMASHITA6, Masahiro HAITSUKA6, Tatsuya TAKESHITA7, Eiji SHIBATA8, Kunio DOBASHI9, Satomi KAMEO10, Muneyuki MIYAGAWA11, Masaaki KANIWA12, Takahiko YOSHIDA13, Tetsuhito FUKUSHIMA14 and Kohtaro YUTA15,16
1Department of Environmental Health, School of Medicine, University of Fukui, Fukui, Japan, 2Department of Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan,
3Department of Environ-mental Health, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan, 4Kumamoto University, Graduate School of Health Sciences, School of Health Sciences,
5Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan, 6Daicel Corporation, Ltd., Himeji, Japan, 7Department of Public Health, School of Medicine, Wakayama Medical University, Wakayama, Japan,
8Department of Hygiene, Aichi Medical University, Nagakute, Japan, 9School of Health Sciences, Faculty of Medicine, Gunma University, Maebashi, Japan, 10Department of Public Health, Gunma University Graduate School of Medicine, Maebashi, Japan,
11National Institute of Occupational Safety and Health, Kawasaki, Japan, 12Division of Medical Devices, National Institute of Health Sciences, Tokyo, Japan, 13Deaprtment of Health Science, School of Medicine, Asahikawa Medical University, Asahikawa, Japan,
14Department of Hygiene and Preventive Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan 15Fujitsu Limited, Tokyo, Japan, 16In Silico Data Ltd., Narashino, Japan


J Oral Tissue Engin 2011;9(3):167-173

SYNOPSIS
Skin sensitization is also related to the dental field. In addition, the regeneration of skin and mucous membranes of the lips may be consulted from the patient. In silico assessment of skin sensitization is increasingly needed owing to the problems concerning animal welfare, as well as excessive time consumed and cost involved in the development and testing of new chemicals. We could perfectly classify skin sensitizers (positive/negative) using a newly developed K-step Yard sampling (KY) methods (U.S. Patent No. 7725413, 2010). Therefore, the KY methods could be applied to qualitative structure-toxicity relationships (QSTR) study on classifying and predicting samples.
A total of 593 compounds (419 positive sensitizers and 174 negative sensitizers) were used in this study. Parameters were generated from 2-D and 3-D structures of compounds. All of the 1015 parameters generated were reduced by various feature selection methods. KY methods were performed using ADMEWORKS/ModelBuilder software. All 593 compounds were perfectly classified by 3 steps. Discriminant function of each step was a linear dicriminant function, the Iterative Least Squares linear discriminant (TILSQ). KY methods were referred to as a meta-algorithm approach because it requires ordinary data analysis methods to generate discriminant functions.
KY methods were the repetition of removal of gray zone of samples and reclassification of them to attain no gray zone (100% classification) at final step. This methods always attain perfect classification at final step, even though samples are large number, large of structural diversity or highly overlapped on the sample space.
KY methods are promising tool in QSTR technology.

Key words: skin sensitization, qualitative structure-toxicity relationships (QSTR), K-step Yard sampling (KY) methods, animal study