{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:34:26Z","timestamp":1760574866083,"version":"build-2065373602"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing that focuses on protein binding. The ADRA is a skin sensitization test that solves problems associated with the direct peptide reactivity assay. However, when utilizing the ADRA to evaluate highly hydrophobic substances with octanol\/water partition coefficients (logKow) of &gt;6, the test substances may not dissolve in the reaction solution, which can prevent the accurate assessment of skin sensitization. Therefore, we developed the ADRA\u2013organic solvent (ADRA\u2010OS) reaction system, which is a novel skin sensitization test that enables the assessment of highly hydrophobic substances with a logKow of &gt;6. We discovered that the organic solvent ratio, the triethylamine concentration, and the ethylenediaminetetraacetic acid disodium salt dihydrate concentration participate in reactions with the nucleophile <jats:italic>N<\/jats:italic>\u2010(2\u2010(1\u2010naphthyl)acetyl)\u2010<jats:sc>l<\/jats:sc>\u2010cysteine (NAC) and sensitizers that are used in ADRA and in stabilizing NAC. Thus, we determined the optimal reaction composition of the ADRA\u2010OS according to L<jats:sub>9<\/jats:sub> (3<jats:sup>3<\/jats:sup>) orthogonal array experiments. Using this test, we assessed 14 types of highly hydrophobic substances. When we compared the results with ADRA, we found that ADRA\u2010OS reaction system has high solubility for highly hydrophobic substances and that it has a high predictive capacity (sensitivity: 63%, specificity: 100%, accuracy: 79%). The implication of the results is that the novel ADRA\u2010OS reaction system should provide a useful method for assessing the skin sensitization of highly hydrophobic substances with a logKow of &gt;6.<\/jats:p>","DOI":"10.1002\/jat.4152","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T12:54:14Z","timestamp":1614344054000},"page":"1634-1648","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Amino acid derivative reactivity assay\u2013organic solvent reaction system: A novel alternative test for skin sensitization capable of assessing highly hydrophobic substances"],"prefix":"10.1002","volume":"41","author":[{"given":"Hiroaki","family":"Yamaga","sequence":"first","affiliation":[{"name":"Safety Science Research Laboratories Lion Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Safety Science Research Laboratories Lion Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Fujita","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Safety Evaluation Center Fujifilm Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Safety Science Research Laboratories Lion Corporation  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"57","article-title":"Problems and countermeasures of alternative methods of skin sensitization test","volume":"9","author":"Aiba S.","year":"2020","journal-title":"Fragrance Journal"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3948"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0536.2007.00944.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2016.07.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19280610879"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","unstructured":"European Parliament(2016).Consolidated Version of the REACH Regulation. 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