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Evaluation of combinations of in vitro sensitization test descriptors for the artificial neural network‐based risk assessment model of skin sensitization
Author(s) -
Hirota Morihiko,
Fukui Shiho,
Okamoto Kenji,
Kurotani Satoru,
Imai Noriyasu,
Fujishiro Miyuki,
Kyotani Daiki,
Kato Yoshinao,
Kasahara Toshihiko,
Fujita Masaharu,
Toyoda Akemi,
Sekiya Daisuke,
Watanabe Shinichi,
Seto Hirokazu,
Takenouchi Osamu,
Ashikaga Takao,
Miyazawa Masaaki
Publication year - 2015
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3105
Subject(s) - local lymph node assay , skin sensitization , sensitization , predictive value , medicine , immunology
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. Copyright © 2015 John Wiley & Sons, Ltd.

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