Effect of Ionic Liquids on Zebrafish (Danio rerio) Viability, Behavior, and Histology; Correlation between Toxicity and Ionic Liquid Aggregation

Abstract

The effect of 11 common amidinium, imidazolium, and phosphonium based ionic liquids (ILs) on zebrafish (Danio rerio) and Chinese hamster ovary cells (CHO) was investigated with specific emphasis on the effect of anion and cation chain length and aggregation of phosphonium based ILs. Viability and behavioral alteration in the locomotor activity and place preference, after IL treatment of 5 days postfertilization larvae, was recorded. Behavior and histological damage evaluation was performed for adult fish in order to get insight into the long-term effects of two potential biomass-dissolving ILs, [DBNH][OAc] and [P4441][OAc]. To get an understanding of how IL aggregation is linked to the toxicity of ILs, median effective concentrations (EC50) and critical micelle concentrations (CMC) were determined. The long-chain ILs were significantly more toxic than the short-chain ones, and the anion chain length was shown to be less significant than the cation chain length when assessing the impact of ILs on the viability of the organisms. Furthermore, most of the ILs were as monomers when the EC50 was reached. In addition, the ILs used in the long-term tests showed no significant effect on the zebrafish behavior, breeding, or histology, within the used concentration range.

Effects of phosphonium-based ionic liquids on phospholipid membranes studied by small-angle X-ray scattering

“…Trioctylmethylphosphonium acetate ([P8881][OAc]; M=445.9 g·mol -1 ) was synthesized as described previously in (Holding et al, 2014;Labafzadeh et al, 2015 ), was synthesized as described in our previous article (Ruokonen et al, 2016).…”

“…Zeta potential measurements were conducted at 20 °C, and a dielectric constant of 80.4 (for water) and a viscosity value of 1.0031 cP (for water) were used in the calculations. The applied electric field strength was 150 V·cm (Dusa et al, 2015) and that of [P14444][OAc] is 0.89 mM in water and 0.32 mM in sodium phosphate buffer (pH 7.4; ionic strength 10 mM) (Ruokonen et al, 2016 [OAc] resulted in a decrease of the intensity, as seen when comparing the intensities of the first and second diffraction peak to the reference. Despite this, the size of the scattering 205 region (the correlation length in the direction of membrane normal), as determined from the FWHM of these peaks, changed only little in all the samples.…”

“…The toxicity results from human corneal epithelial cells and E. coli cells correlated with changes in the liposome surface charge and shape, indicating that the cytotoxicity is in part due to interactions between the ILs and the phospholipid bilayer. The concentration at which ILs start to form micelles (critical micelle concentration, CMC) correlates well with the concentration at which the ILs start to disrupt unilamellar vesicles (LUV) (Dusa et al, 2015;Ruokonen et al, 2016). Clearly, the effects 70 of ILs on lipid bilayers are more destructive at concentrations where IL micelles form.…”

“…The IL toxicity increases with increasing lipophilicity and thereby length of the 40 lipophilic cationic groups (Mikkola et al, 2015). However, the type of anion also plays a role, particularly for bulky anions with long and/or branched alkyl chains (Egorova and Ananikov, 2014;Petkovic et al, 2010;Ruokonen et al, 2016). The resulting effect is therefore a combination of the properties of the anion and cation.…”

Homogenous esterification of cellulose pulp in [DBNH][OAc]

“…Several recent articles have also assessed the toxicity of different biomass dissolving ionic liquids. Those with shorter anion and cation alkyl chain length are considered to be of lower toxicity (Ruokonen et al 2016;Witos et al 2017). This also corresponds with the better capability to dissolve cellulose as cellulose dissolution capability typically decreases as cation or anion volume gets too large (Isik et al 2014).…”