Journal
TOXICOLOGY IN VITRO
Volume 46, Issue -, Pages 194-202Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2017.09.025
Keywords
Ionic liquid; Bis(trifluoromethanesulfonyl)imide, TFSI; Dermal toxicity; ROS; 3D skin model
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Funding
- National Research Foundation of Korea [NRF-2015R1D1A1A01057931]
- Ministry of Health & Welfare, Republic of Korea [HN15C0102]
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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-acetyleysteine. 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.
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