title: 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.
abstract: 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.
authors.affiliation: Kao Corporation, Ichikai-Machi, Haga-Gun, Tochigi, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takenouchi
authors.affiliation: Kanebo Cosmetics Inc., Odawara, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Shiho
authors.initials: S
authors.lastname: Fukui
authors.affiliation: Kanebo Cosmetics Inc., Odawara, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: KOSE Corporation, Itabashi-ku, Tokyo, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kurotani
authors.affiliation: KOSE Corporation, Itabashi-ku, Tokyo, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Imai
authors.affiliation: Cosmos Technical Center Co., Ltd., Itabashi-ku, Tokyo, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Cosmos Technical Center Co., Ltd., Itabashi-ku, Tokyo, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Daiki
authors.initials: D
authors.lastname: Kyotani
authors.affiliation: Nippon Menard Cosmetic Co., Ltd., Nishi-ku, Nagoya, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Fujifilm Corporation, Minamiashigara-shi, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kasahara
authors.affiliation: Fujifilm Corporation, Minamiashigara-shi, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Pola Chemical Industries, Inc., Totsuka-ku, Yokohama, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Akemi
authors.initials: A
authors.lastname: Toyoda
authors.affiliation: Lion Corporation, Odawara, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sekiya
authors.affiliation: Lion Corporation, Odawara, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: P&G Japan K.K., Higashinada-ku, Kobe, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Seto
authors.affiliation: Shiseido Research Center, Shiseido Co. Ltd., Tsuzuki-ku, Yokohama-shi, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Morihiko
authors.initials: M
authors.lastname: Hirota
authors.affiliation: Shiseido Research Center, Shiseido Co. Ltd., Tsuzuki-ku, Yokohama-shi, Kanagawa, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Takao
authors.initials: T
authors.lastname: Ashikaga
authors.affiliation: Kao Corporation, Ichikai-Machi, Haga-Gun, Tochigi, Japan.|Working Group for In Vitro Skin Sensitization Evaluation in Japan Cosmetic Industry Association.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D002460:Cell Line; D003358:Cosmetics / Q000737:chemistry / Q000633:toxicity*; D023381:Endpoint Determination; D006801:Humans; D023441:Local Lymph Node Assay; D010455:Peptides / Q000737:chemistry; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012867:Skin / Q000187:drug effects*; D012882:Skin Tests; D012995:Solubility; D018675:Toxicity Tests; D014867:Water / Q000737:chemistry
chemical_list: D003358:Cosmetics; D010455:Peptides; D014867:Water
keywords: DEREK; DPRA; Skin sensitization; h-CLAT; in vitro test; integrated testing strategy; sequential testing strategy; test battery