Report on the Assessment of Contact Hypersensitivity to 1-Ethyl-3-Methylimidazolium Chloride in Female BALB/c Mice (CAS No. 65039-09-0)
Report Date: July 2010
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
1-Ethyl-3-methylimidazolium chloride is classified as an ionic liquid, a class of compounds which are salts of organic cations with melting points generally below 100°C (Kulacki and Lamberti, 2008). Ionic liquids have been recognized as alternative solvents to replace volatile organic solvents (e.g., benzene and toluene) in catalysis, synthesis, and separation processes and in the manufacture of nanomaterials (Yu et al., 2009; Landry et al., 2005). These compounds are representative of the most common cation classes of ILs being investigated, are the starting materials for many other ILs, and are being produced commercially. Several of these ILs have been nominated to the NTP for a toxicological evaluation. Of these, EMI was selected for an evaluation of its irritant and sensitization potential. The LC50 of EMI is 100 mg/l in fish after 48 hr of exposure. Limited toxicity studies are available for EMI. There is no information available on the potential of EMI to induce sensitization. However, a related compound, ethyl-methyl-imidazolium ethylsulfate, was not considered to be a sensitizer or irritant when evaluated by a manufacturer.
The objective of this study was to determine the sensitizing potential of 1-ethy-3-methylimidazolium chloride when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the combined local lymph node assay and irritancy assay. Based upon the potential toxicity of the chloride moiety and on solubility tests completed by the sponsor, the highest achievable concentration of EMI in acetone: olive oil (4:1; AOO) was 50% (w/v). Accordingly, the concentrations of EMI used for the combined LLNA and IRR assays were 50%, 25%, 12.5%, and 6.25%. In the LLNA, EMI at concentrations of 6.25%-50% did not induce significant increases in lymph node cell proliferation when compared to the vehicle control. In addition, EMI was not an irritant at concentrations up to 50%, as demonstrated by a lack of effect on ear thickness at 24 hr following the last dermal exposure.
To further confirm the negative LLNA response, the Mouse Ear Swelling Test was performed following exposure to EMI. In the sensitization phase, two concentrations of EMI (25% and 50%) were used, and a concentration of 50% was applied during the challenge phase. There was no significant difference in the percent ear swelling at 24 and 48 hrs following challenge in mice treated with EMI when compared to the vehicle irritancy control.
In conclusion, under the experimental conditions utilized in this study of female BALB/c mice, EMI was negative in the LLNA, the irritancy assay, and the MEST.
Kulacki K.J., Lamberti G.A. (2008). Toxicity of imidazolium ionic liquids to fresh water algae. Green Chem 10: 104-110.
Yu Y-H, Soriano AN, Li M-H. (2009). Heat capacities and electrical conductivities of 1-ethyl-3-methylimidazolium-based ionic liquids. J. Chem. Thermodynamics 41: 103-108.
Landry T.D., Brooks K., Poche D., & Woolhiser M. (2005). Acute toxicity profile of 1-Butyl-3-Methylimidazolium Chloride. Bull. Environ. Conm. Toxicol. 74: 559-565.