Nicola Wood and Gill Stephens discuss the methods available for testing and predicting toxicity in ionic liquids.

Ionic liquids have numerous applications in industrial processes where they have been heralded as a green alternative to conventional solvents. They have low vapour pressures and are rarely flammable or explosive meaning that they present fewer hazards or environmental risks in closed processes. Unfortunately, the first generation of ionic liquids, based on imidazolium or pyridinium cations, turned out to be just as toxic as conventional solvents, and sometimes even worse. As ionic liquids are now increasingly finding use in consumer goods, such as batteries, textiles and cosmetics, a thorough understanding of potential health hazards and environmental impact is essential. 

The beauty of ionic liquids is that combining different cations and anions produces wholly new ionic liquids with their own unique structures and properties. Several million possible structures are available, which presents a great opportunity to engineer solvents with specific properties for different applications. But it also presents an unusual problem - synthesising, characterising and testing the seemingly limitless possibilities is a near impossible task.

A growing number of non-toxic and biodegradable ionic liquids have been discovered recently. Ionic liquids in this class are truly green, since their environmental impact is minimal. There can be no doubt that many more environmentally friendly structures remain to be discovered - the new challenge is to find them, as it is still very difficult to predict an ionic liquid's toxicity. 

Modelling of existing data coupled with high throughput screening of new ionic liquids are used to point the way to useful structures and have shown that toxicity can correlate very strongly with the lipophilicity of the cation. Recently, work has shown that changing the anion also has a very significant impact on toxicity. But many more structures will need to be tested for ecotoxicity before there are sufficient data to develop reliable models to predict toxicity. 

In the meantime, high throughput synthesis and screening is the main route to discover non-toxic ionic liquids. The toxicity screens need to be designed for maximum throughput, minimal costs, convenience and minimal use of materials to cope with the large numbers of structures. Many different types of toxicity screens are available and each test has to be done with a specific living organism. But different organisms respond differently to chemical toxicants so a number of complementary tests are needed to determine the likely environmental impact. A detailed ecotoxicity test battery was recently developed that begins with an initial high throughput screen, which selects the most promising results for further tests using a hierarchial system with increasing biological complexity. 

Commercially available cell viability text kits use smaller volumes of ionic liquid but can be expensive and require specialised equipment to read the results. More recently, the Agar diffusion test, which is widely used to test the effects of antibioitics on microorganisms has been adapted to measure ionic liquid toxicity. It is extremely easy to use, requires minimal experience of microbiological methods, and the apparatus is simple. Ionic liquid is added to a filter paper disc that is transferred to a prepare lawn of microbial cells. If a clear zone is formed around the paper, the ionic liquid is toxic and the size of the zone indicates the level of toxicity. It would be possible to use this simple test in synthetic chemistry labs which would make it possible to report preliminary data on toxicity alongside the more conventional characterisation protocols for new ionic liquids. As a result, it will become possible to select the most promising new ionic liquids for detailed ecotoxicity testing at a much earlier stage, accelerating the introduction of new non-toxic ionic liquids. 

Overall, the future of ionic liquids seems bright. The structural diversity is so large that, just like any other chemicals, some are toxic and some are benign. Non-toxic ionic liquids are out there - we just have to find them. 

Read more in the perspective 'Accelerating the discovery of biocompatible ionic liquids' in PCCP. 

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