Safety study of protic ionic liquids to human health: an alternative to conventional solvents.
Ionic liquids. Protic ionic liquids. Toxicity. Cells. Wound healing.
Ionic liquids are non-volatile organic salts that, under standardized conditions, remain in a liquid state and are composed of organic cations and organic or inorganic anions. They have a wide industrial application and sustainable profile and, generally, they are called as "green solvents", however, despite this denomination, there is insufficient information about their aspects related to their toxicity to the environment and to humans. In this context, this work aimed to evaluate the toxicological aspects of some ionic liquids through in vitro bioassays, inaddition to trying to understand their effects on cells, seeking possible biological applications. For this purpose, seventeen protic ionic liquids were synthesized and analyzed by in vitro assays of: cytotoxicity in metabolizing cells (HepG2) and skin cells (HaCat and HDFa); morphological observation of HaCat cells exposed to these liquids; and eye irritation in chicken egg's chorioallantoic membrane (HET-CAM). In order to study a possible biological application, the wound healing potential in HDFa cells was also evaluated. The results obtained were promising, since, in general, the ionic liquids showed a low cytotoxic effect, obtaining IC50 values between 8 and 390 mM, approximately. In addition, it was possible to observe its effect on cells, causing an increase or decrease in volume and/or rupture of cell membrane in HaCat cells, due to osmotic pressure. The eye irritation test showed that the ionic liquids composed of citric acid did not cause eye irritation, while thirteen of them were characterized as mild or moderate irritants, and it is possible to suggest, based on this test, their safe use in living organisms, although there are reservations. It was also confirmed, from a quantitative analysis by the ImageJ software, the classification of eye irritation by the analysis of grayscale images. In addition, no sample tested was able to prevent the healing process evaluated in vitro, which is another indication of safety and, still, the ionic liquid based on oxalic acid stands out for being able to improve cell migration. Therefore, it was possible to conclude that the protic ionic liquids evaluated in this work are, in general, safe, less toxic to human cells than conventionally used solvents and the collected results contribute significantly to science, as they indicate safety parameters of these compounds, related to their chemical characteristics and concentrations and reinforce the need to continue these studies. Also, in this work, a new direction of research is suggested using protic ionic liquids, seeking biological effects for them.