{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:34:28Z","timestamp":1789929268796,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,10]],"date-time":"2017-12-10T00:00:00Z","timestamp":1512864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens\u2122 and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens\u2122, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES\u2010M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential.<\/jats:p>","DOI":"10.1002\/jat.3558","type":"journal-article","created":{"date-parts":[[2017,12,10]],"date-time":"2017-12-10T21:38:42Z","timestamp":1512941922000},"page":"514-526","source":"Crossref","is-referenced-by-count":44,"title":["Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens\u2122 and in silico structure alert parameter"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4110-5015","authenticated-orcid":false,"given":"Morihiko","family":"Hirota","sequence":"first","affiliation":[{"name":"Shiseido Global Innovation Center Shiseido Co. Ltd.  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama\u2010shi Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Ashikaga","sequence":"additional","affiliation":[{"name":"Shiseido Global Innovation Center Shiseido Co. Ltd.  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama\u2010shi Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kouzuki","sequence":"additional","affiliation":[{"name":"Shiseido Global Innovation Center Shiseido Co. Ltd.  2\u20102\u20101 Hayabuchi, Tsuzuki\u2010ku Yokohama\u2010shi Kanagawa 224\u20108558 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(99)00005-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271141"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2007.10.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2005.10.012"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2310\/6620.2008.07018","article-title":"Preservatives and skin sensitization quantitative risk assessment","volume":"19","author":"Basketter D. 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