{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:55:29Z","timestamp":1790564129050,"version":"4.1.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Research Institute for Fragrance Materials, Inc"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2015,8]]},"DOI":"10.1016\/j.yrtph.2015.03.001","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T03:36:12Z","timestamp":1425872172000},"page":"683-693","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":408,"title":["Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied"],"prefix":"10.1016","volume":"72","author":[{"given":"David W.","family":"Roberts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Api","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Safford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon F.","family":"Lalko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yrtph.2015.03.001_b0005","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1021\/tx0256634","volume":"16","author":"Alvarez-S\u00e1nchez","year":"2003","journal-title":"Chem. Res. Toxicol."},{"issue":"1","key":"10.1016\/j.yrtph.2015.03.001_b0010","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.yrtph.2007.10.008","article-title":"Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients","volume":"52","author":"Api","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0015","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1021\/tx0601004","article-title":"Mechanistic applicability domains for nonanimal-based prediction of toxicological end points: general principles and application to reactive toxicity","volume":"19","author":"Aptula","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0020","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1021\/tx050075m","article-title":"Skin sensitization: reaction mechanistic applicability domains for structure\u2013activity relationships","volume":"18","author":"Aptula","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0025","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1021\/tx9000336","article-title":"Chemical mechanisms for skin sensitization by aromatic compounds with hydroxy and amino groups","volume":"22","author":"Aptula","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0030","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-0536.2006.00913.x","article-title":"Hydroperoxides form specific antigens in contact allergy","volume":"55","author":"Brared Christensson","year":"2006","journal-title":"Contact Dermatitis"},{"issue":"3","key":"10.1016\/j.yrtph.2015.03.001_b0035","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0015-6264(76)80522-6","article-title":"Estimation of toxic hazard \u2013 a decision tree approach","volume":"16","author":"Cramer","year":"1978","journal-title":"Food Cosmet. Toxicol."},{"issue":"5","key":"10.1016\/j.yrtph.2015.03.001_b0040","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1021\/tx4000655","article-title":"Predicting skin sensitization potency for Michael acceptors in the LLNA using quantum mechanics calculations","volume":"26","author":"Enoch","year":"2013","journal-title":"Chem. Res. Toxicol."},{"issue":"2","key":"10.1016\/j.yrtph.2015.03.001_b0045","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1021\/tx700322g","article-title":"Quantitative and mechanistic read across for predicting the skin sensitization potential of alkenes acting via Michael addition","volume":"21","author":"Enoch","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0050","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1006\/rtph.2001.1498","article-title":"ICCVAM evaluation of the murine local lymph node assay. III. Data analyses completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods","volume":"34","author":"Haneke","year":"2001","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0055","series-title":"Physical Organic Chemistry","author":"Hine","year":"1962"},{"key":"10.1016\/j.yrtph.2015.03.001_b0060","series-title":"Physical Organic Chemistry","author":"Isaacs","year":"1995"},{"key":"10.1016\/j.yrtph.2015.03.001_b0065","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1021\/tx7002239","article-title":"Allergic contact dermatitis \u2013 formation, structural requirements, and reactivity of skin sensitizers","volume":"21","author":"Karlberg","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0070","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/cod.12127","article-title":"Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers: prehaptens and prohaptens","volume":"69","author":"Karlberg","year":"2013","journal-title":"Contact Dermatitis"},{"key":"10.1016\/j.yrtph.2015.03.001_b0075","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1600-0536.2011.01899.x","article-title":"Clinical and experimental studies of octocrylene\u2019s allergenic potency","volume":"64","author":"Karlsson","year":"2011","journal-title":"Contact Dermatitis"},{"issue":"1","key":"10.1016\/j.yrtph.2015.03.001_b0080","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.fct.2003.08.006","article-title":"Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet","volume":"42","author":"Kroes","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0085","first-page":"643","article-title":"Studies on the sensitization of animals with simple chemical compounds","volume":"64","author":"Landsteiner","year":"1936","journal-title":"J. Exp. Med."},{"issue":"9","key":"10.1016\/j.yrtph.2015.03.001_b0090","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0278-6915(96)00049-X","article-title":"Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern","volume":"34","author":"Munro","year":"1996","journal-title":"Food Chem. Toxicol."},{"issue":"12","key":"10.1016\/j.yrtph.2015.03.001_b0095","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1021\/tx1002707","article-title":"Chemical basis for the extreme skin sensitization potency of (E)-4-(ethoxymethylene)-2-phenyloxazol-5(4H)-one","volume":"23","author":"Natsch","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0100","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1021\/tx2003678","article-title":"Relating skin sensitizing potency to chemical reactivity: reactive Michael acceptors inhibit NF-kB signaling and are less sensitizing than SNAr- and SN2- reactive chemicals","volume":"24","author":"Natsch","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0105","unstructured":"NLM Toxnet HSDB. <http:\/\/toxnet.nlm.nih.gov\/cgi bin\/sis\/search\/a?dbs+hsdb:@term+@DOCNO+7730>."},{"key":"10.1016\/j.yrtph.2015.03.001_b0110","series-title":"The Chemistry of Cyanates and their Thio Derivatives","author":"Patai","year":"1977"},{"key":"10.1016\/j.yrtph.2015.03.001_b0115","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1600-0536.1975.tb05472.x","article-title":"Contact sensitization of guinea pigs with unsaturated and halogenated sultones","volume":"1","author":"Ritz","year":"1975","journal-title":"Contact Dermatitis"},{"key":"10.1016\/j.yrtph.2015.03.001_b0120","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.yrtph.2015.01.009","article-title":"Estimating skin sensitization potency from a single dose LLNA","volume":"71","author":"Roberts","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0125","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/jat.1289","article-title":"Determinants of skin sensitisation potential","volume":"28","author":"Roberts","year":"2008","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0130","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1021\/tx400355n","article-title":"Electrophilic reactivity and skin sensitization potency of SNAr electrophiles","volume":"27","author":"Roberts","year":"2014","journal-title":"Chem. Res. Toxicol."},{"issue":"3","key":"10.1016\/j.yrtph.2015.03.001_b0135","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1021\/tx800431x","article-title":"High throughput kinetic profiling approach for covalent binding to peptides: application to skin sensitization potency of Michael Acceptor electrophiles","volume":"22","author":"Roberts","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0140","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0022-5193(82)90199-0","article-title":"The derivation of quantitative correlations between skin sensitisation and physico-chemical parameters for alkylating agents and their application to experimental data for sultones","volume":"99","author":"Roberts","year":"1982","journal-title":"J. Theor. Biol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0145","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/tx060102o","article-title":"Mechanistic applicability domains for non-animal based toxicological endpoints. QSAR analysis of the Schiff Base applicability domain for skin sensitization","volume":"19","author":"Roberts","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0150","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1021\/tx060121y","article-title":"Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published dataset of 106 chemicals tested in the mouse local lymph node assay","volume":"20","author":"Roberts","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0155","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1021\/tx700024w","article-title":"Mechanistic applicability domain classification of a Local Lymph Node Assay dataset for skin sensitization","volume":"20","author":"Roberts","year":"2007","journal-title":"Chem. Res. Toxicol."},{"issue":"9","key":"10.1016\/j.yrtph.2015.03.001_b0160","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1021\/tx700169w","article-title":"TIMES-SS \u2013 a mechanistic evaluation of an external validation study using reaction chemistry principles","volume":"20","author":"Roberts","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0165","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1021\/tx600330u","article-title":"Electrophilic reactions of skin sensitizing sultones","volume":"20","author":"Roberts","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0170","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.yrtph.2008.02.010","article-title":"The dermal sensitisation threshold \u2013 a TTC approach for allergic contact dermatitis","volume":"51","author":"Safford","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0175","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.yrtph.2011.03.009","article-title":"Refinement of the dermal sensitisation threshold (DST) approach using a larger dataset and incorporating mechanistic chemistry domains","volume":"60","author":"Safford","year":"2011","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0180","article-title":"Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive","author":"Safford","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2015.03.001_b0185","series-title":"Organic Chemistry","author":"Wade","year":"2012"}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230015000483?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230015000483?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T11:31:27Z","timestamp":1537788687000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230015000483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["S0273230015000483"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2015.03.001","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2015,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2015.03.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}