Skin sensitization risk assessment model using artificial neural network analysis of data from multiple in vitro assays.
The sensitizing potential of chemicals is usually identified and characterized using in vivo methods such as the murine local lymph node assay (LLNA). Due to regulatory constraints and ethical concerns, alternatives to animal testing are needed to predict skin sensitization potential of chemicals. For this purpose, combined evaluation using multiple in vitro and in silico parameters that reflect different aspects of the sensitization process seems promising. We previously reported that LLNA thresholds could be well predicted by using an artificial neural network (ANN) model, designated iSENS ver.1 (integrating in vitro sensitization tests version 1), to analyze data obtained from two in vitro tests: the human Cell Line Activation Test (h-CLAT) and the SH test. Here, we present a more advanced ANN model, iSENS ver.2, which additionally utilizes the results of antioxidant response element (ARE) assay and the octanol-water partition coefficient (LogP, reflecting lipid solubility and skin absorption). We found a good correlation between predicted LLNA thresholds calculated by iSENS ver.2 and reported values. The predictive performance of iSENS ver.2 was superior to that of iSENS ver.1. We conclude that ANN analysis of data from multiple in vitro assays is a useful approach for risk assessment of chemicals for skin sensitization.
Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
Kyoko
K
Tsujita-Inoue
Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan. Electronic address: morihiko.hirota@to.shiseido.co.jp.
Morihiko
M
Hirota
Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
Takao
T
Ashikaga
Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
Tomomi
T
Atobe
Shiseido Research Center, Shiseido Co. Ltd., 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
Hirokazu
H
Kouzuki
Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
Setsuya
S
Aiba
D000485:Allergens / Q000633:toxicity*; D061745:Antioxidant Response Elements; D001681:Biological Assay; D003877:Dermatitis, Contact / Q000276:immunology*; D006801:Humans; D016571:Neural Networks, Computer; D018570:Risk Assessment
D000485:Allergens
Antioxidant response element, ARE; Artificial neural network; Risk assessment; SH test; Skin sensitization; h-CLAT