A comparison of the effects of prenatal exposure of CD-1 mice to three imidazolium-based ionic liquids

Ionic liquids (ILs; salts with melting points below 100 degrees C) exhibit wide liquid ranges, non-flammability, and thermal stability among other properties. These unique salts are best known as "green" alternatives to traditional volatile organic solvents, which are utilized in both academia and industry. Our current study compares the developmental toxicity potential of three representative ionic liquids, with various chain lengths: 1-ethyl-3-methylimidazolium chloride ([C(2)mim]Cl), 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl), and 1-decyl-3methylimidazolium chloride ([C(10)mim]Cl).

This study indicates that [C(4)mim]Cl and [C(10)mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium-based ILs is influenced by alkyl chain length.

From gestation days (GD) 6-16, mated CD-1 mice were orally dosed with one of the following: 1,000, 2,000, or 3,000 mg/kg/day [C(2)mim]Cl; 113, 169, or 225 mg/kg/day [C(4)mim]Cl; 50, 75, or 100 mg/kg/day [C(10)mim]Cl; or the vehicle only. Dams were sacrificed on GD 17, and their litters were examined for adverse effects.

Fetal weight was significantly decreased in the two highest dosage groups exposed to [C(4)mim]Cl and [C(10)mim]Cl in comparison with their controls, but the [C(2)mim]Cl treated groups were not affected. An apparent teratogenic effect was associated with both [C(4)mim]Cl and [C(10)mim]Cl, as the offspring exhibited certain uncommon morphological defects. However, the incidences of malformations were low and no correlation between incidence and dosage could be made. No morphological defects were observed in any of the [C(2)mim]Cl-treated groups, despite maternal morbidity at the highest dosage level. Conclusions: This study indicates that [C(4)mim]Cl and [C(10)mim]Cl may have adverse effects on development at high maternal exposures and strongly supports the supposition that the toxicity of imidazolium-based ILs is influenced by alkyl chain length.