A research group led by Associate Professor Kosuke Kuroda and doctoral student Yusuke Kubota (concurrently a researcher at Suntory Holdings Limited) of Faculty of Biological Science and Technology, Institute of Science and Engineering of Kanazawa University, in a joint study with Suntory Holdings Limited, has discovered that by using the low-toxicity, cell-friendly zwitterionic liquid, OE₂imC₃C. OE₂imC₃C enabled to carry out in vitro (cell) testing of food additives, which was previously difficult to do using conventional dimethyl sulfoxide (DMSO).

Ellagic acid is used as a dietary supplement due to its anticancer, antioxidant, and antidiabetic properties. On the other hand, its insolubility in water and DMSO poses a technical challenge for toxicity testing. In fact, in vivo studies showed no hepatotoxicity, while in vitro studies showed hepatocellular damage at high concentrations, and the reason for this discrepancy was unknown. In this study, it was clarified that the toxicity observed in vitro was due to physical damage to cells caused by ellagic acid crystals that did not dissolve in DMSO or precipitated. Furthermore, we confirmed that the use of a new solvent, OE₂imC₃C (Figure 1), developed by Kuroda et al. improved the solubility of ellagic acid (Table 1) and the reliability of in vitro tests.

Based on the results obtained in this study, the in vitro test method using OE₂imC₃C is a useful technique that not only enables the evaluation of poorly soluble substances in the food and pharmaceutical fields, but also contributes to the reduction of animal experiments, and is expected to be put to practical use in the future and to expand its application areas.

The results of this research were published online in “The Journal of Toxicological Sciences“ on March 1, 2026 at 00:00 (JST).

_{Figure 1: Chemical structures of OE₂imC₃C (developed by Kuroda’s group) and DMSO (a commercially available low‑toxicity organic solvent)  　
Kubota Y. et al.,J. Toxicol. Sci.(2026), DOI:10.2131/jts.51.227（CC BY 4.0)}

_{Table 1: Comparison of the solubility of ellagic acid in OS and DMSO
Kubota Y. et al.,J. Toxicol. Sci.(2026), DOI:10.2131/jts.51.227（CC BY 4.0)}

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Journal : The Journal of Toxicological Sciences
Researcher’s Information： Kosuke Kuroda