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Test battery with the human cell line activation test, direct peptide reactivity assay and DEREK based on a 139 chemical data set for predicting skin sensitizing potential and potency of chemicals
Author(s) -
Takenouchi Osamu,
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,
Hirota Morihiko,
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.3127
Subject(s) - potency , test (biology) , skin sensitization , reactivity (psychology) , test set , chemical compound , chemistry , computational biology , toxicology , medicine , biochemistry , computer science , in vitro , immunology , biology , toxicity , artificial intelligence , organic chemistry , pathology , paleontology , alternative medicine , sensitization
To develop a testing strategy incorporating the human cell line activation test (h‐CLAT), direct peptide reactivity assay (DPRA) and DEREK, we created an expanded data set of 139 chemicals (102 sensitizers and 37 non‐sensitizers) by combining the existing data set of 101 chemicals through the collaborative projects of Japan Cosmetic Industry Association. Of the additional 38 chemicals, 15 chemicals with relatively low water solubility (log Kow > 3.5) were selected to clarify the limitation of testing strategies regarding the lipophilic chemicals. Predictivities of the h‐CLAT, DPRA and DEREK, and the combinations thereof were evaluated by comparison to results of the local lymph node assay. When evaluating 139 chemicals using combinations of three methods based on integrated testing strategy (ITS) concept (ITS‐based test battery) and a sequential testing strategy (STS) weighing the predictive performance of the h‐CLAT and DPRA, overall similar predictivities were found as before on the 101 chemical data set. An analysis of false negative chemicals suggested a major limitation of our strategies was the testing of low water‐soluble chemicals. When excluded the negative results for chemicals with log Kow > 3.5, the sensitivity and accuracy of ITS improved to 97% (91 of 94 chemicals) and 89% (114 of 128). Likewise, the sensitivity and accuracy of STS to 98% (92 of 94) and 85% (111 of 129). Moreover, the ITS and STS also showed good correlation with local lymph node assay on three potency classifications, yielding accuracies of 74% (ITS) and 73% (STS). Thus, the inclusion of log Kow in analysis could give both strategies a higher predictive performance. Copyright © 2015 John Wiley & Sons, Ltd.