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Toxicol In Vitro. 2018 Feb;46:194-202. doi: 10.1016/j.tiv.2017.09.025. Epub 2017 Sep 25.

Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models.

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College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
Department of Public Health Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:
College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address:


Ionic liquids have gained increasing attention in the chemical industry as potential green substitutes for traditional solvents. However, little is known about toxicity of ionic liquids on the skin, a major exposure portal to toxic substances. Here, we evaluated dermal toxicity of ionic liquids using human keratinocyte and fibroblast cell line, 3D reconstructed human epidermis, and full-thickness model to investigate underlying mechanisms. Cytotoxicity of ionic liquids was evaluated for representative anions, [TFSI], [PF6], [BF4], and [DCA], as well as for cations, [EMIM], [BMPY], [TBA] and [Zn], in human keratinocyte cell line, HaCaT, and human dermal fibroblasts. In our results, significant cytotoxicity was induced by ionic liquids with [TFSI] in both cell lines. Notably, cytotoxicity of [TFSI] containing ionic liquids was comparable to xylene, a toxic conventional organic solvent. Fluorescent and flow cytometric analysis revealed that [TFSI]-exposed cells underwent necrotic cell death. Reactive oxygen species (ROS) was increased while the amount of glutathione was decreased by [TFSI] in dose-dependent manner, which was reversed by antioxidant, N-acetylcysteine. In 3D reconstructed human epidermis and full-thickness model, a single application of [TFSI] induced toxicity although it was minimal and largely limited to epidermal layer. Collectively, these results demonstrated potential dermal toxicity of ionic liquids.


3D skin model; Bis(trifluoromethanesulfonyl)imide, TFSI; Dermal toxicity; Ionic liquid; ROS

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