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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.

Author information

1
College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
2
Department of Public Health Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
3
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: kitaek@yuhs.ac.
4
College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address: kmlim@ewha.ac.kr.

Abstract

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.

KEYWORDS:

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

PMID:
28958837
DOI:
10.1016/j.tiv.2017.09.025
[Indexed for MEDLINE]

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