The mode of toxic action of ionic liquids: Narrowing down possibilities using high-throughput, in vitro cell-based bioassays.

Autor: Bae E; Institute of Water Chemistry, Dresden University of Technology, D-01062 Dresden, Germany., Beil S; Institute of Water Chemistry, Dresden University of Technology, D-01062 Dresden, Germany., König M; Department of Cell Toxicology, Helmholtz Centre for Environmental Research-UFZ, D-04318 Leipzig, Germany., Stolte S; Institute of Water Chemistry, Dresden University of Technology, D-01062 Dresden, Germany., Escher BI; Department of Cell Toxicology, Helmholtz Centre for Environmental Research-UFZ, D-04318 Leipzig, Germany; Environmental Toxicology, Department of Geosciences, Eberhard Karls University Tübingen, D-72076 Tübingen, Germany., Markiewicz M; Institute of Water Chemistry, Dresden University of Technology, D-01062 Dresden, Germany. Electronic address: marta.markiewicz@tu-dresden.de.
Jazyk: angličtina
Zdroj: Environment international [Environ Int] 2024 Nov; Vol. 193, pp. 109089. Date of Electronic Publication: 2024 Oct 20.
DOI: 10.1016/j.envint.2024.109089
Abstrakt: Growing concerns about the environmental impact of ionic liquids (ILs) have spurred research into their (eco)toxic effects, but studies on their mode of toxic action (MOA) still remain limited. However, understanding the MOA and identifying structural features responsible for enhanced toxicity is crucial for characterising the hazard and designing safer alternatives. Therefore, 45 ILs, with systematically varied chemical structures, were tested for cytotoxicity and two specific endpoints in reporter gene assays targeting the Nrf2-ARE mediated oxidative stress response (AREc32) and aryl hydrocarbon receptor activation (AhR-CALUX). While none of the ILs activated the reporter genes, cytotoxicity was high and markedly different between cell lines. Seven and 25 ILs proved more cytotoxic than predicted by baseline toxicity model in the AREc32 and the AhR-CALUX assays, respectively. The length of the side chain and headgroup structures of ILs altered the MOA of ILs. Cellular metabolism of the ILs, investigated by LC-MS/MS, showed side-chain oxidation of the long-chain quaternary ammonium compounds in AhR-CALUX cells and, to a lower extent, in AREc32 cells, however, this transformation could not explain the high cytotoxicity. Effect data for 72 ILs for ten endpoints retrieved from the Tox21 database identified the inhibition of aromatase activity and of mitochondrial membrane potential as potential MOAs. However, in vitro fluorimetric assays for these endpoints demonstrated that effects were activated in a non-specific manner, probably through cytotoxicity. Although many of the ILs tested induced cytotoxicity at concentrations lower than baseline toxicity, the specific MOAs responsible could not be identified. Alternatively, we suggest that the descriptors currently used may fail to define the affinity of ILs for cells. Testing of the affinity of ILs for a diverse range of biomolecules is needed to accurately describe their interactions with cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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