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

Jee hyun Hwang, Hyeonji Park, Dal Woong Choi, Ki Taek Nam, Kyung Min Lim

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish
Pages (from-to)194-202
Number of pages9
JournalToxicology in Vitro
StatePublished - Feb 2018

Bibliographical note

Funding Information:
This work is supported by the National Research Foundation of Korea (Grant No. NRF-2015R1D1A1A01057931 ) and by the Ministry of Health &Welfare, Republic of Korea (Grant No. HN15C0102 ).

Publisher Copyright:
© 2017 Elsevier Ltd


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


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