title: Evaluation of combinations of in vitro sensitization test descriptors for the artificial neural network-based risk assessment model of skin sensitization.
abstract: The skin sensitization potential of chemicals has been determined with the use of the murine local lymph node assay (LLNA). However, in recent years public concern about animal welfare has led to a requirement for non-animal risk assessment systems for the prediction of skin sensitization potential, to replace LLNA. Selection of an appropriate in vitro test or in silico model descriptors is critical to obtain good predictive performance. Here, we investigated the utility of artificial neural network (ANN) prediction models using various combinations of descriptors from several in vitro sensitization tests. The dataset, collected from published data and from experiments carried out in collaboration with the Japan Cosmetic Industry Association (JCIA), consisted of values from the human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA), SH test and antioxidant response element (ARE) assay for chemicals whose LLNA thresholds have been reported. After confirming the relationship between individual in vitro test descriptors and the LLNA threshold (e.g. EC3 value), we used the subsets of chemicals for which the requisite test values were available to evaluate the predictive performance of ANN models using combinations of h-CLAT/DPRA (N = 139 chemicals), the DPRA/ARE assay (N = 69), the SH test/ARE assay (N = 73), the h-CLAT/DPRA/ARE assay (N = 69) and the h-CLAT/SH test/ARE assay (N = 73). The h-CLAT/DPRA, h-CLAT/DPRA/ARE assay and h-CLAT/SH test/ARE assay combinations showed a better predictive performance than the DPRA/ARE assay and the SH test/ARE assay. Our data indicates that the descriptors evaluated in this study were all useful for predicting human skin sensitization potential, although combinations containing h-CLAT (reflecting dendritic cell-activating ability) were most effective for ANN-based prediction.
authors.affiliation: Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa, 224-8558, Japan.
authors.forename: Morihiko
authors.initials: M
authors.lastname: Hirota
authors.affiliation: Kanebo Cosmetics Inc., 3-28, Kotobukicho 5-chome, Odawara, Kanagawa, 250-0002, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Fukui
authors.affiliation: Kanebo Cosmetics Inc., 3-28, Kotobukicho 5-chome, Odawara, Kanagawa, 250-0002, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Kose Corporation, 1-18-4 Azusawa, Itabashi-ku, Tokyo, 174-0051, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kurotani
authors.affiliation: Kose Corporation, 1-18-4 Azusawa, Itabashi-ku, Tokyo, 174-0051, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Imai
authors.affiliation: Cosmos Technical Center Co., Ltd., 3-24-3 Hasune, Itabashi-ku, Tokyo, 174-0046, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Cosmos Technical Center Co., Ltd., 3-24-3 Hasune, Itabashi-ku, Tokyo, 174-0046, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Kyotani
authors.affiliation: Nippon Menard Cosmetic Co., Ltd., 2-7, Torimi-cho, Nishi-ku, Nagoya, 451-0071, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Fujifilm Corporation, 210, Nakamura, Minamiashigara-shi, Kanagawa, 250-0193, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kasahara
authors.affiliation: Fujifilm Corporation, 210, Nakamura, Minamiashigara-shi, Kanagawa, 250-0193, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Pola Chemical Industries, Inc., 560 Kashio-cho, Totsuka-ku, Yokohama, 244-0812, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Toyoda
authors.affiliation: Lion Corporation, 100, Tajima, Odawara, Kanagawa, 256-0811, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sekiya
authors.affiliation: Lion Corporation, 100, Tajima, Odawara, Kanagawa, 256-0811, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: P&G Japan K.K., 1-17, Koyo-cho Naka, Higashinada-ku, Kobe, 658-0032, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Seto
authors.affiliation: Kao Corporation, 2606, Akabane, Ichikai-Machi, Haga-Gun, Tochigi, 321-3497.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takenouchi
authors.affiliation: Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa, 224-8558, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ashikaga
authors.affiliation: Kao Corporation, 2606, Akabane, Ichikai-Machi, Haga-Gun, Tochigi, 321-3497.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D023441:Local Lymph Node Assay; D016571:Neural Networks, Computer; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012867:Skin / Q000378:metabolism*; D012882:Skin Tests / Q000379:methods*
keywords: ARE; DPRA; JCIA; SH test; artificial neural network; h-CLAT; risk assessment; skin sensitization