{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:46:17Z","timestamp":1790520377041,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T00:00:00Z","timestamp":1465516800000},"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":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It is widely accepted that substances must have a molecular weight (MW)\u00a0&lt;\u00a0500 to penetrate effectively through the skin to induce sensitization. Roberts <jats:italic>et al<\/jats:italic>. (2012. <jats:italic>Contact Dermatitis<\/jats:italic> 68: 32\u201341) evaluated a data set of 699 substances taken from the TIMES\u2010SS expert system and identified that of the 13 substances with a MW\u00a0&gt;\u00a0500, five were sensitizers. This provided good evidence to refute such a MW 500 threshold. While Roberts <jats:italic>et al<\/jats:italic>. (2012) made a convincing case that the MW\u00a0&gt;\u00a0500 cut\u2010off was not a true requirement for sensitization, the number of counter examples identified were too few to draw any statistical conclusions. This updated analysis systematically interrogated a large repository of sensitization information collected under the EU REACH regulation. A data set of 2904 substances that had been tested for skin sensitization, using guinea pigs and\/or mice were collected. The data set contained 197 substances with a MW\u00a0&gt;\u00a0500; 33 of these were skin sensitizers. Metal containing complexes, reaction products and mixtures were excluded from further consideration. The final set of 14 sensitizers substantiated the original findings. The study also assessed whether the same reaction chemistry principles established for low MW sensitizers applied to chemicals with a MW\u00a0&gt;\u00a0500. The existing reaction chemistry considerations were found appropriate to rationalize the sensitization behaviour of the 14 sensitizers with a MW\u00a0&gt;\u00a0500. The existence of the MW 500 threshold, based on the widespread misconception that the ability to penetrate efficiently the stratum corneum is a key determinant of skin sensitization potential and potency, was refuted. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3348","type":"journal-article","created":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T02:21:51Z","timestamp":1465525311000},"page":"105-116","source":"Crossref","is-referenced-by-count":34,"title":["What determines skin sensitization potency: Myths, maybes and realities. The 500 molecular weight cut\u2010off: An updated analysis"],"prefix":"10.1002","volume":"37","author":[{"given":"Jeremy M.","family":"Fitzpatrick","sequence":"first","affiliation":[{"name":"National Center for Computational Toxicology (NCCT) US Environmental Protection Agency (US EPA)  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Pharmacy Liverpool John Moores University  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-9689","authenticated-orcid":false,"given":"Grace","family":"Patlewicz","sequence":"additional","affiliation":[{"name":"National Center for Computational Toxicology (NCCT) US Environmental Protection Agency (US EPA)  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-011-0693-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.11.013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2000.009003165.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1965.01600080079017"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.01.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00420-002-0418-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004200050407"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10915810591000631"},{"key":"e_1_2_7_10_1","unstructured":"EC.2006.Regulation (EC) No. 1907\/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration Evaluation Authorisation and Restriction of Chemicals (REACH) establishing a European Chemicals Agency amending Directive 1999\/45\/EC and repealing Council Regulation (EEC) No. 793\/93 and Commission Regulation (EC) No. 1488\/94 as well as Council Directive 76\/769\/EEC and Commission Directives 91\/155\/EEC 93\/67\/EEC 93\/105\/EC and 2000\/21\/EC. 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