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Human exposure occurs through dermal or oral routes. In rodents, several ILs were reported to induce dermal toxicity, irritation, and sensitization. Due to the potential for occupational exposure, and industrial use as nonvolatile solvents, 1\u2010ethyl\u20103\u2010methylimidazolium chloride (EMIM, 6.25% to 50% v\/v), 1\u2010butyl\u20103\u2010methylimidazolium chloride (BMIM, 3.12% to 12.5% v\/v), 1\u2010butyl\u20101\u2010methylpyrrolidinium chloride (BMPY, 0.825% to 6.25% v\/v), and <jats:italic>N<\/jats:italic>\u2010butylpyridinium chloride (NBuPY, 0.825% to 12.5% v\/v) were nominated to the National Toxicology Program and evaluated for skin sensitization. The test compound was applied to the ears of female BALB\/c mice daily for 3\u2009days in a primary irritancy (IRR)\/local lymph node assay (LLNA). Sensitization was assessed in vitro in the direct peptide reactivity assay (DPRA), KeratinoSens\u2122 assay, and human cell line activation test (h\u2010CLAT). In the LLNA, the butylated ILs, BMIM, and BMPY were more potent than NBuPY (butylated) or EMIM (ethylated), which was neither an irritant nor a sensitizer. NBuPY induced skin irritation in vivo at \u22653.12% (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.01), and sensitization in vitro in the KeratinoSens\u2122 assay and h\u2010CLAT, but was negative for sensitization in vivo and in the DPRA. Although SI3 was not achieved, dermal treatment with 12.5% BMIM or 6.25% BMPY increased (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.01) lymph node cell proliferation in the LLNA. In vitro, BMIM was positive for sensitization in the h\u2010CLAT, and BMPY was positive in the h\u2010CLAT and KeratinoSens\u2122 assay; both were negative in the DPRA. Integrated data analyses, weighted toward in vivo data, suggested that BMIM and BMPY may induce weak to mild sensitization.<\/jats:p>","DOI":"10.1002\/jat.4224","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T07:49:08Z","timestamp":1630136948000},"page":"392-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of skin sensitization induced by four ionic liquids"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-8240","authenticated-orcid":false,"given":"Rachel P.","family":"Frawley","sequence":"first","affiliation":[{"name":"Division of the National Toxicology Program National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dori R.","family":"Germolec","sequence":"additional","affiliation":[{"name":"Division of the National Toxicology Program National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Burleson Research Technologies, Inc.  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Gulledge","sequence":"additional","affiliation":[{"name":"Burleson Research Technologies, Inc.  Morrisville North Carolina USA"},{"name":"StrideBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wimolnut","family":"Manheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Kimber","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Shockley","sequence":"additional","affiliation":[{"name":"Division of Intramural Research National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn F.","family":"Harris","sequence":"additional","affiliation":[{"name":"DLH Corporation  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hooth","sequence":"additional","affiliation":[{"name":"Division of the National Toxicology Program National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Ryan","sequence":"additional","affiliation":[{"name":"Division of the National Toxicology Program National Institute of Environmental Health Sciences  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b01463"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271141"},{"key":"e_1_2_8_4_1","first-page":"492","article-title":"Integration of primary irritation with the LLNA","volume":"72","author":"Anderson P.","year":"2003","journal-title":"The Toxicologist"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2011.07.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15569520701556647"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0536.2008.01444.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2012.05.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.3.761"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2013.10.019"},{"key":"e_1_2_8_11_1","unstructured":"Chemical Effects in Biological Systems (CEBS)(2021a).(Genetic Toxicity Data). 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