{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:51:58Z","timestamp":1780926718254,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T00:00:00Z","timestamp":1488240000000},"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":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dermal contact with chemicals may lead to an inflammatory reaction known as allergic contact dermatitis. Consequently, it is important to assess new and existing chemicals for their skin sensitizing potential and to mitigate exposure accordingly. There is an urgent need to develop quantitative non\u2010animal methods to better predict the potency of potential sensitizers, driven largely by European Union (EU) Regulation 1223\/2009, which forbids the use of animal tests for cosmetic ingredients sold in the EU. A Nearest Neighbours <jats:italic>in silico<\/jats:italic> model was developed using an in\u2010house dataset of 1096 murine local lymph node (LLNA) studies. The EC3 value (the effective concentration of the test substance producing a threefold increase in the stimulation index compared to controls) of a given chemical was predicted using the weighted average of EC3 values of up to 10 most similar compounds within the same mechanistic space (as defined by activating the same Derek skin sensitization alert). The model was validated using previously unseen internal (<jats:italic>n<\/jats:italic>\u2009=\u200945) and external (<jats:italic>n<\/jats:italic>\u2009=\u2009103) data and accuracy of predictions assessed using a threefold error, fivefold error, European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) and Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classifications. In particular, the model predicts the GHS skin sensitization category of compounds well, predicting 64% of chemicals in an external test set within the correct category. Of the remaining chemicals in the previously unseen dataset, 25% were over\u2010predicted (GHS 1A predicted: GHS 1B experimentally) and 11% were under\u2010predicted (GHS 1B predicted: GHS 1A experimentally). Copyright \u00a9 2017 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3448","type":"journal-article","created":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T03:22:52Z","timestamp":1488252172000},"page":"985-995","source":"Crossref","is-referenced-by-count":35,"title":["A quantitative <i>in silico<\/i> model for predicting skin sensitization using a nearest neighbours approach within expert\u2010derived structure\u2013activity alert spaces"],"prefix":"10.1002","volume":"37","author":[{"given":"Steven J.","family":"Canipa","sequence":"first","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn L.","family":"Chilton","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Hemingway","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-6722","authenticated-orcid":false,"given":"Donna S.","family":"Macmillan","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alun","family":"Myden","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Plante","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael E.","family":"Tennant","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Vessey","sequence":"additional","affiliation":[{"name":"Lhasa Limited  Granary Wharf House 2 Canal Wharf, Leeds LS11 5PS UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Steger\u2010Hartmann","sequence":"additional","affiliation":[{"name":"Bayer Pharma  Muellerstrasse 178 Wedding, Berlin D\u201013342 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Gould","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  1 Squibb Drive New Brunswick NJ 08903 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedd","family":"Hillegass","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  1 Squibb Drive New Brunswick NJ 08903 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Etter","sequence":"additional","affiliation":[{"name":"Firmenich S.A.  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