Evaluation of (eco)toxicity and biodegradability of short aliphatic protic ionic liquids

Abstract

Ionic liquids (ILs) are a fairly new and very promising group of compounds. They are often considered as environmentally benign substitutes for traditional volatile organic solvents due to their attractive properties and physicochemical characteristics (e.g. non-volatility, high thermal stability and very good and versatile solving capacity). The ILs are salts composed entirely of ions (cations and anions) with a melting point below 100°C and they are liquid in a wide range of temperatures. The ILs are usually described as "green", but they are chemical products, and as such have to fulfill the requirements of the European Community regulation on chemicals and their safe use called Registration, Evaluation, Authorization, and Restriction of Chemical Substances (REACH). Due to their immeasurably low vapor pressure ILs cannot be found in the atmosphere, but their water solubility is often high and they are stable, so they can end up in industrial and laboratory effluents and consequently cause water and soil contamination. The analyzed ILs include representatives of a new family of protic ionic liquids (PILs) derived from mono-, di- and triethanolamine and aliphatic organic acids, and some of the most frequently used imidazolium and pyridinium based aprotic ionic liquids (AILs). In order to evaluate the environmental impact of these ILs, various (eco)toxicity tests were performed. The aquatic ecotoxicity tests included target organisms: marine bacteria Vibrio fischeri, green algae Pseudokirchneriella subcapitata and aquatic plant Lemna minor. The terrestrial ecotoxicity tests evaluated the toxic effects on terrestrial plants (onion Allium cepa, grass Lolium perenne and radish Raphanus sativus) and soil microorganisms involved in carbon and nitrogen transformation. Two additional test systems with an enzyme (acetylcholinesterase inhibition) and isolated leukemia rat cells IPC-81 (cytotoxicity) were performed in order to provide a more in-depth evaluation of toxicity. Ready biodegradability in water and soil was also studied. The number of combinations of cations and anions forming ionic liquids is practically infinite, so they can be custom designed in order to suite the desired application. But the complete information on their environmental impact is still not available. The quantitative structure-activity relationship (QSAR) modelling can allow reliable prediction of toxicity and it helps to avoid unnecessary animal experiments, which is why the use of in silico models and QSAR is strongly encouraged by European Chemicals Agency (ECHA) and REACH. As it is clearly impossible to analyze the toxicity of so many compounds, the application of QSAR models could speed up the process of ecotoxicological evaluation and indicate the potential toxicity of new ILs before they are considered for commercialization. In this thesis, a group contribution QSAR model was used in order to predict the (eco)toxicity of eight previously untested PILs that belong to the new family. The prediction was made for five (eco)toxicity tests (Microtox®, Pseudokirchneriella subcapitata and Lemna minor growth inhibition test, and Acetylcholinestherase inhibition and Cell viability assay with IPC-81 cells). The PILs proved to be non-toxic in most of the performed tests. The EC50 values for AILs are up to several orders of magnitude lower than the ones for the PILs and they show much lower biodegradation potential. The most toxic ILs are the most complex ones in both of the analyzed groups. The findings of the thesis indicate that the PILs with simpler and lineal structure can be considered as environmentally safer than the AILs predominately used up to date, which have bulky organic anions with long alkyl chain substituents.

Els líquids iònics (ILs) són un grup de compostos bastant nou i molt prometedor. Sovint són considerats com a substituts ambientalment benignes de dissolvents orgànics volàtils tradicionals a causa de les seves propietats fisicoquímiques atractives. Encara que els ILs tenen un perfil potencialment "verd", són bàsicament productes químics, i com a tal, han de complir amb els requisits de la legislació vigent sobre productes químics de la Unió Europea anomenada Registre, Avaluació, Autorització i Restricció de Substàncies Químiques (REACH). La informació completa sobre l’impacte ambiental d’ILs encara no està disponible. Els líquids iònics analitzats inclouen representants d'una nova família de líquids iònics pròtics (PILs) derivats de mono-, di- i trietanolamina i àcids orgànics alifàtics, i alguns representants freqüentment utilitzats de la família de líquids iònics apròtics (AILs), derivats de l’imidazoli i del piridini. Per tal de determinar l'impacte mediambiental es van realitzar els assaigs d'ecotoxicitat aquàtica (amb Vibrio fischeri, Pseudokirchneriella subcapitata i Lemna minor) i terrestre (amb Allium cepa, Lolium perenne i Raphanus sativus, i amb els microorganismes del sòl participants en els cicles de carboni i nitrogen). Per obtenir una avaluació més detallada de la toxicitat, es van realitzar dues proves de toxicitat addicionals: inhibició de l'acetilcolinesterasa i citotoxicitat. La biodegradabilitat en aigua i sòl es va determinar també. Es va utilitzar un model de relació estructura-activitat quantitativa (QSAR) de contribució de grups per predir l’(eco)toxicitat dels PILs de la nova família que no s’havien analitzat prèviament. Els PILs van resultar ser no tòxics en la majoria de les proves realitzades. Els AILs analitzats van ser més tòxics que els PILs, amb valors de CE50 diversos ordres de magnitud inferiors i van manifestar un baix potencial de biodegradabilitat. Els ILs amb l’estructura més complexa van ser els més tòxics en ambdós grups analitzats. Els resultats d'aquesta tesi indiquen que els ILs amb estructura més simple i lineal poden ser considerats com a més segurs per al medi ambient que els habitualment utilitzats fins ara, que contenen cations més voluminosos i substituents de cadena alquílica llarga.