{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:00:04Z","timestamp":1760576404519,"version":"build-2065373602"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["2U01FD004246\u201006"],"award-info":[{"award-number":["2U01FD004246\u201006"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Twenty\u2010four pure fragrance ingredients of concern as potential skin sensitizers were previously subjected to degradation studies and evaluated using the high throughput with dansyl cysteamine (HTS\u2010DCYA) method. The experimental results showed that two\u2010thirds of the 24 fragrance ingredients underwent chemical degradation. In some cases, such degradation was accompanied by an increase in thio\u2010reactivity. These results prompted us to investigate the reactivity of the same ingredients using the direct peptide reactivity assay (DPRA). In the present work, the 24 chemicals were subjected to forced degradation for 150\u00a0days, and evaluated with both DPRA and HTS\u2010DCYA methods. At the end of the study, four and eight compounds remained non\u2010reactive in the DPRA and DCYA assay, respectively. Coumarin, benzyl salicylate, benzyl cinnamate and hexyl cinnamal were found unreactive in both assays, while cinnamal, cinnamyl alcohol, hydroxycitronellal and lilial were found negative in the DCYA but positive in the DPRA method. The incongruity in reactivity of these four compounds was attributed to a possible role of pro\u2010oxidants formed upon degradation, resulting in depletion of peptide without formation of apparent covalent adducts with the test chemical. To validate this hypothesis, the effect of hydrogen peroxide as model pro\u2010oxidant on both lysine\u2010 and cysteine\u2010heptapeptide depletion in the DPRA method was thus investigated. The obtained results showed little effect of oxidative conditions on lysine depletion, while cysteine depletion was significantly affected by concentrations above 1.1\u00a0mg\/L of hydrogen peroxide. Overall, both in chemico methods confirmed chemical instability should be considered when assessing the skin sensitization potential of (un)known chemicals with alternative methods.<\/jats:p>","DOI":"10.1002\/jat.3732","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T06:59:20Z","timestamp":1539673160000},"page":"398-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-6813","authenticated-orcid":false,"given":"Cristina","family":"Avonto","sequence":"first","affiliation":[{"name":"National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy The University of Mississippi  University, MS 38677 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy The University of Mississippi  University, MS 38677 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-5373","authenticated-orcid":false,"given":"Amar G.","family":"Chittiboyina","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy The University of Mississippi  University, MS 38677 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislav","family":"Vukmanovic","sequence":"additional","affiliation":[{"name":"Office of Cosmetics and Colors, Center for Food Safety and Applied Nutrition Food and Drug Administration  College Park MD 20740 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-4643","authenticated-orcid":false,"given":"Ikhlas A.","family":"Khan","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy The University of Mississippi  University, MS 38677 USA"},{"name":"Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy The University of Mississippi  University, MS 38677 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.09.027"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5b00530"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.09.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2012.05.013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700638"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx960087v"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cosmetics3020019"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5b00098"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700017v"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.08.014"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0536.2011.01962.x"},{"key":"e_1_2_9_13_1","unstructured":"ICH. (1998).Guideline Q1B: Photostability testing of new active substances and medicinal products."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.12127"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ffj.3210"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2007.03.016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2868"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.12009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx400428f"},{"key":"e_1_2_9_20_1","unstructured":"OECD. (2012).The adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins. Part 1: Scientific Evidence. OECD Environment Health and Safety publications Series on Testing and Assessment No. 168."},{"key":"e_1_2_9_21_1","unstructured":"OECD. (2015a).Test No. 442C: In chemico skin sensitisation: direct peptide reactivity assay (DPRA). OECD Guidelines for the Testing of Chemicals Section 4. Paris: OECD Publishing."},{"key":"e_1_2_9_22_1","unstructured":"OECD. (2015b).Test No. 442D: In vitro skin sensitisation: ARE\u2010Nrf2 luciferase test method.https:\/\/doi.org\/10.1787\/9789264229822\u2010en"},{"key":"e_1_2_9_23_1","unstructured":"OECD. (2017).Test No. 442E: in vitro skin sensitisation: human cell line activation test (h\u2010CLAT).https:\/\/doi.org\/10.1787\/9789264264359\u2010en"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3479"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201200855"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201300843"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2000.9025"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3127"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2014.12.008"},{"key":"e_1_2_9_30_1","first-page":"302","article-title":"Cross\u2010sensitization patterns in guinea pigs between cinnamaldehyde, cinnamyl alcohol and cinnamic acid","volume":"69","author":"Weibel H.","year":"1989","journal-title":"Acta Dermato\u2010Venereologica."}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:05:44Z","timestamp":1760555144000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/jat.3732"],"URL":"https:\/\/doi.org\/10.1002\/jat.3732","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"type":"print","value":"0260-437X"},{"type":"electronic","value":"1099-1263"}],"subject":[],"published":{"date-parts":[[2018,10,16]]},"assertion":[{"value":"2018-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}