Review of the toxic effects of ionic liquids.

Interest in ionic liquids (ILs), called green or designer solvents, has been increasing because of their excellent properties such as thermal stability and low vapor pressure; thus, they can replace harmful organic chemicals and help several industrial fields e.g., energy-storage materials production and biomaterial pretreatment. However, the claim that ILs are green solvents should be carefully considered from an environmental perspective. ILs, given their minimal vapor pressure, may not directly cause atmospheric pollution. However, they have the potential to cause adverse effects if leaked into the environment, for instance if they are spilled due to human mistakes or technical errors. To estimate the risks of ILs, numerous ILs have had their toxicity assessed toward several micro- and macro-organisms over the past few decades. Since the toxic effects of ILs depend on the method of estimating toxicity, it is necessary to briefly summarize and comprehensively discuss the biological effects of ILs according to their structure and toxicity testing levels. This can help simplify our understanding of the toxicity of ILs. Therefore, in this review, we discuss the key findings of toxicological information of ILs, collect some toxicity data of ILs to different species, and explain the influence of IL structure on their toxic properties. In the discussion, we estimated two different sensitivity values of toxicity testing levels depending on the experiment condition, which are theoretical magnitudes of the inherent sensitivity of toxicity testing levels in various conditions and their changes in biological response according to the change in IL structure. Finally, some perspectives, future research directions, and limitations to toxicological research of ILs, presented so far, are discussed.

Ionic liquid-assisted cellulose coating of chitosan hydrogel beads and their application as drug carriers.

The present study proposes a simple yet effective method of cellulose coating onto chitosan (CS) hydrogel beads and application thereof as drug carriers. The beads were coated with cellulose dissolved in 1-ethyl-3-methylimidazolium acetate, an ionic liquid (IL) via a one-pot one-step process. Water molecules present in the CS beads diffused outward upon contact with the cellulose-IL mixture and acted as an anti-solvent. This allowed the surface of the beads to be coated with the regenerated cellulose. The regenerated cellulose was characterized by FE-SEM, FT-IR, and XRD analyses. To test potential application of the cellulose-coated CS hydrogel beads as a drug carrier, verapamil hydrochloride (VRP), used as a model drug, was impregnated into the beads. When the VRP-impregnated beads were immersed in the simulated gastric fluid (pH 1.2), the VRP was released in an almost ideal linear pattern. This easily fabricated cellulose-coated CS beads showed the possibility for application as carriers for drug release control.

A clinic-based direct real-time fluorescent reverse transcription loop-mediated isothermal amplification assay for influenza virus.

Seasonal influenza virus causes acute respiratory tract infections, which can be severe in children and the elderly. At present, rapid influenza diagnostic tests (RIDTs) are popular at clinical sites because they enable early diagnosis and avoid unnecessary use of antibiotics; in addition, high risk patients with underlying disease can be given antiviral drugs. However, the sensitivity and specificity of some of those tests are relatively poor. To overcome these problems, nucleic acid-based molecular point-of-care tests have been developed; however, they are significantly more expensive than RIDTs. Previously, the authors developed real-time reverse transcription loop-mediated isothermal amplification (rRT-LAMP) assays using a quenching primer to detect influenza viruses. However, the assay is limited to laboratory use because it requires a nucleic acid purification step and preparation of reaction mixtures on ice. Therefore, the authors developed and validated direct rRT-LAMP assays that require no nucleic acid purification steps using commercial RNA isolation kits, and no storage and handling of reagents on ice. These assays can be performed within 10-30 min and require only mixing a clinical specimen with extraction reagent followed by addition of a lyophilized detection reagent. The established assay showed high sensitivity and specificity when validated using 310 clinical specimens. Thus, the assay is a powerful tool for molecular diagnosis of seasonal influenza virus infection in the clinic.

Environmental Concerns Regarding Ionic Liquids in Biotechnological Applications.

Ionic liquids provide challenges and opportunities for sustainable industrial developments. However, the toxic impacts of ionic liquids reported by many researchers cannot be overlooked. Therefore, in this chapter, we introduce the antimicrobial activities of ionic liquids in bioprocesses and, in greater detail, we discuss their environmental impacts, including the toxicity, biodegradability, bioaccumulation, and mobility of ionic liquids. We believe that this presented information will support colleagues engaged in ionic liquid-related fields. Graphical Abstract.

Three degradation pathways of 1-octyl-3-methylimidazolium cation by activated sludge from wastewater treatment process.

The biodegradability and degradation pathways of 1-octyl-3-methylimidazolium cation [OMIM](+) by microbial community of wastewater treatment plant in Jeonju city, Korea were investigated. It was found that [OMIM](+) could be easily degraded by the microbial community. New degradation products and pathways of [OMIM](+) were identified, which are partially different from previous results (Green Chem. 2008, 10, 214-224). For the analysis of the degradation pathways and intermediates, the mass peaks observed in the range m/z of 50-300 were screened by using a tandem mass spectrometer (MS), and their fragmentation patterns were investigated by MS/MS. Surprisingly, we found three different degradation pathways of [OMIM](+), which were separated according to the initially oxidized position i.e. middle of the long alkyl chain, end of the long alkyl chain, and end of the short alkyl chain. The degradation pathways showed that the long and short alkyl chains of [OMIM](+) gradually degraded by repeating oxidation and carbon release. The results presented here shows that [OMIM](+) can be easily biodegraded through three different degradation pathways in wastewater treatment plants.

Structural effects of ionic liquids on microalgal growth inhibition and microbial degradation.

In the present study, we investigated structural effects of various ionic liquids (ILs) on microalgal growth inhibition and microbial biodegradability. For this, we tested pyridinium- and pyrrolidinium-based ILs with various alkyl chain lengths and bromide anion, and compared the toxicological effects with log EC50 values of imidazolium-based IL with the same alkyl chains and anion from literature. Comparing determined EC50 values of cationic moieties with the same alkyl chain length, pyridinium-based ILs were found to be slightly more toxic towards the freshwater green alga, Pseudokirchneriella subcapitata, than a series of pyrrolidinium and imidazolium except to 1-octyl-3-methylimidazolium bromide. Concerning the biodegradation study of 12 ILs using the activated sludge microorganisms, the results showed that the pyridinium derivatives except to 1-propyl-3-methylpyridinium cation were degraded. Whereas in case of imidazolium- and pyrrolidinium-based compounds, only n-hexyl and n-octyl substituted cations were fully degraded but no significant biodegradation was observed for the short chains (three and four alkyl chains).

Food waste-to-energy conversion technologies: current status and future directions.

Food waste represents a significantly fraction of municipal solid waste. Proper management and recycling of huge volumes of food waste are required to reduce its environmental burdens and to minimize risks to human health. Food waste is indeed an untapped resource with great potential for energy production. Utilization of food waste for energy conversion currently represents a challenge due to various reasons. These include its inherent heterogeneously variable compositions, high moisture contents and low calorific value, which constitute an impediment for the development of robust, large scale, and efficient industrial processes. Although a considerable amount of research has been carried out on the conversion of food waste to renewable energy, there is a lack of comprehensive and systematic reviews of the published literature. The present review synthesizes the current knowledge available in the use of technologies for food-waste-to-energy conversion involving biological (e.g. anaerobic digestion and fermentation), thermal and thermochemical technologies (e.g. incineration, pyrolysis, gasification and hydrothermal oxidation). The competitive advantages of these technologies as well as the challenges associated with them are discussed. In addition, the future directions for more effective utilization of food waste for renewable energy generation are suggested from an interdisciplinary perspective.

Heterogeneous catalyst-assisted thermochemical conversion of food waste biomass into 5-hydroxymethylfurfural.

A novel thermochemical conversion route has been developed that yields 5-hydroxymethylfurfural (HMF) from food waste biomass (FWB) in the presence of a heterogeneous catalysts (zirconium phosphate (ZrP)). The ZrP catalyst was prepared by precipitation followed by calcination at 400 (ZrP-400) and 600 °C (ZrP-600) and was characterized by SEM, XRD, XPS, N2 sorption and NH3-TPD. The optimized reaction conditions were identified to maximize HMF yield by varying the type of catalyst, the catalyst loading and the reaction time. The highest HMF yield achieved was 4.3%. On average 33% higher yield for ZrP-600 was obtained compared to that for ZrP-400, which might be due to higher number of acid sites on ZrP-600. The ZrP catalyst was easily regenerated by thermal treatment and showed stable activity upon its reuse. Preliminary calculations of the "minimum selling price" of HMF suggest that it is economically attractive to make this industrially-relevant chemical from FWB.

Knowledge, attitudes, practices and emotional reactions among residents of avian influenza (H5N1) hit communities in Vietnam.

BACKGROUND: Awareness of individuals' knowledge and predicting their behavior and emotional reactions is crucial when evaluating clinical preparedness for influenza pandemics with a highly pathogenic virus. Knowledge, attitude, and practice (KAP) relating to avian influenza (H5N1) virus infection among residents in communities where H5N1 patients occurred in Vietnam has not been reported. METHODS AND PRINCIPAL FINDINGS: Face-to-face interviews including KAP survey were conducted in Bac Kan province, located in the northeast mountainous region of Vietnam. Participants were residents who lived in a community where H5N1 cases have ever been reported (event group, n = 322) or one where cases have not been reported (non-event group, n = 221). Data on emotional reactions of participants and healthcare-seeking behavior after the event in neighboring areas were collected as well as information on demographics and environmental measures, information sources, and KAP regarding H5N1. These data were compared between two groups. Higher environmental risk of H5N1 and improper poultry-handling behaviors were identified in the event group. At the time of the event, over 50% of the event group sought healthcare for flu-like symptoms or because they were scared. Awareness of the event influenced KAP scores. Healthcare-seeking behavior and attention to H5N1 poultry outbreaks diminished in the event group as time passed after the outbreak compared with the non-event group. Factors that motivated participants to seek healthcare sooner were knowledge of early access to healthcare and the risk of eating sick/dead poultry, and perception of the threat of H5N1. CONCLUSIONS: Awareness of H5N1 patients in neighboring areas can provoke panic in residents and influence their healthcare-seeking behavior. Periodic education to share experiences on the occurrence of H5N1 patients and provide accurate information may help prevent panic and infection and reduce mortality. Local conditions should be taken into account when emphasizing the need for early access to healthcare.

Impact of education and network for avian influenza H5N1 in human: knowledge, clinical practice, and motivation on medical providers in Vietnam.

BACKGROUND: Knowledge, clinical practice, and professional motivation of medical providers relating to H5N1 infection have an important influence on care for H5N1 patients who require early diagnosis and early medical intervention. METHODS/PRINCIPAL FINDINGS: Novel educational programs including training and workshops for medical providers relating to H5N1 infection in Vietnam were originally created and implemented in 18 provincial hospitals in northern Vietnam between 2008 and 2010. A self-administered, structured questionnaire survey was conducted in 8 provincial hospitals where both educational training and workshops were previously provided. A total of 326 medical providers, including physicians, nurses, and laboratory technicians who attended or did not attend original programs were enrolled in the survey. Knowledge, clinical attitudes and practice (KAP), including motivation surrounding caring for H5N1 patients, were evaluated. The study indicated a high level of knowledge and motivation in all professional groups, with especially high levels in laboratory technicians. Conferences and educational programs were evaluated to be the main scientific information resources for physicians, along with information from colleagues. The chest radiographs and the initiation of antiviral treatment in the absence of RT-PCR result were identified as gaps in education. Factors possibly influencing professional motivation for caring for H5N1 patients included healthcare profession, the hospital where the respondents worked, age group, attendance at original educational programs and at educational programs which were conducted by international health-related organizations. CONCLUSIONS: Educational programs provide high knowledge and motivation for medical providers in Vietnam caring for H5N1 patients. Additional educational programs related to chest radiographs and an initiation of treatment in the absence of RT-PCR are needed. Networking is also necessary for sharing updated scientific information and practical experiences. These enhanced KAPs by educational programs and integrated systems among hospitals should result in appropriate care for H5N1 patients and may reduce morbidity and mortality.

Impact of educational intervention concerning awareness and behaviors relating to avian influenza (H5N1) in a high-risk population in Vietnam.

BACKGROUND: Early initiation of treatment is essential for treatment of avian influenza A/H5N1 viral infection in humans, as the disease can lead to rapid development of severe pneumonia which can result in death. Contact with infected poultry is known to be a significant risk factor for contraction of H5N1 infection. However, handling and encountering poultry are a part of most peoples' daily lives, especially in rural communities in Vietnam where epidemic outbreaks among poultry have been continuously reported. Enhancing proper knowledge relating to H5N1 and to the importance of early initiation of treatment are crucial. The aim of this study was to develop an effective educational program to enhance awareness of H5N1 and motivate people to access to health care earlier when H5N1 infection is suspected or likely. METHODOLOGY AND PRINCIPAL FINDINGS: A study was conducted in two agricultural communities (intervention and control groups) in the Ninh Binh province in Vietnam, where epidemic outbreaks of avian influenza have recently occurred in birds. A unique educational intervention was developed and provided to the intervention group, and no intervention was provided to the control group. A knowledge, attitude and practice (KAP) survey was conducted in both groups with a face-to-face interview by trained local healthcare workers at time points before and after the educational intervention. KAP scores were compared between the different time points and between the groups. How educational intervention influenced awareness relating to H5N1 and accessibility of healthcare in the population was analyzed. The study indicated an increased awareness of H5N1 and increased reliance on local health care workers. CONCLUSIONS: The novel educational program which was developed for this study impacted awareness of H5N1, and resulted in more people seeking early access to healthcare, and also resulted in earlier medical intervention for patients with H5N1 avian influenza infection in Vietnam.

Environmental fate and toxicity of ionic liquids: a review.

Ionic liquids (ILs) are organic salts with low melting point that are being considered as green replacements for industrial volatile organic compounds. The reputation of these solvents as "environmental friendly" chemicals is based primarily on their negligible vapor pressure. Nonetheless, the solubility of ILs in water and a number of literature documenting toxicity of ILs to aquatic organisms highlight a real cause for concern. The knowledge of ILs behavior in the terrestrial environment, which includes microbial degradation, sorption and desorption, is equally important since both soil and aquatic milieu are possible recipients of IL contamination. This article reviews the achievements and current status of environmental risk assessment of ILs, and hopefully provides insights into this research frontier.

Identification of metabolites involved in the biodegradation of the ionic liquid 1-butyl-3-methylpyridinium bromide by activated sludge microorganisms.

Ionic liquids (ILs) are low melting organic salts that potentially comprise wide application due to their fascinating properties and have emerged as promising "green" replacements for volatile organic solvents. Despite their nonmeasurable vapor pressure, some quantities of ILs will soon be present in effluent discharges since they do have significant solubility in water. Recently, the toxic effects of ILs toward aquatic communities have been intensively investigated, but little information is available concerning the biodegradable properties of these compounds. The objective of this study was to identify the metabolites generated during the biotransformation of 1-butyl-3-methylpyridinium by microorganisms in aerobic activated sludge. The obtained results revealed that the alkylpyridinium salt was metabolized through the sequential oxidization in different positions of the alkyl side chains. High-performance liquid chromatography and mass-spectrometry analyses demonstrated that this biodegradation led to the formation of 1-hydroxybutyl-3-methylpyridinium, 1-(2-hydroxybutal)-3-methylpyridinium, 1-(2-hydroxyethyl)-3-methylpyridinium, and methylpyridine. On the basis of these intermediate products, biodegradation pathways were also suggested. These findings provide the basic information that might be useful for assessing the factors related to the environmental fate and behavior of this commonly used pyridinium IL.

Alkyl-chain length effects of imidazolium and pyridinium ionic liquids on photosynthetic response of Pseudokirchneriella subcapitata.

The toxicities of imidazolium- and pyridinium-based ionic liquids with various alkyl-chain lengths were investigated on the photosynthetic activity of the alga Pseudokirchneriella subcapitata. Our results show that an imidazolium compound with four carbons in the alkyl chain was the least toxic salt, and should be preferred over pyridinium entity.

Effect of imidazolium-based ionic liquids on the photosynthetic activity and growth rate of Selenastrum capricornutum.

Ionic liquids (ILs) are low-melting organic salts that are being researched intensively as possible environmentally friendly replacements for volatile organic solvents. Despite their nonmeasurable vapor pressure, some quantities of ILs soon will be present in effluent discharges because solubility of ILs in water is small, but far from negligible. Therefore, it is important to understand how ILs will influence aquatic ecosystems. In the present study, the toxic effects of imidazolium-based ILs (1-butyl-3-methylimidazolium cation associated with bromide [BMIM] [Br] and tetrafluoroborate [BMIM] [BF4]) to the freshwater green alga Selenastrum capricornutum were investigated. Two approaches were followed to quantify toxicity of these compounds: Analyses of photosynthetic activity and cell proliferation. The obtained data showed that the relative declines of growth rates generally were more pronounced than those of photosynthetic activity. The ecotoxicity of a range of common organic solvents also was examined. It was revealed that both imidazolium-based ILs studied were some orders of magnitude more toxic than methanol, isopropanol, and dimethylformamide. In addition, with respect to IL incorporating perfluorinated anion, EC50 values (concentrations which lead to a 50% reduction of the exposed organisms relative to control) of the previously prepared stock solution were significantly lower compared to those of the freshly made one. This might be due to hydrolytic effects of [BMIM][BF4] leading to fluoride formation, which was confirmed by ion chromatography analysis. This indicates that, after ILs are discharged into the aqueous system, they can become more toxic than expected by laboratory data with fresh ILs.

Microalgal photosynthetic activity measurement system for rapid toxicity assessment.

A systematic biosensor is constructed for the estimation of toxic compounds based on photosynthetic activity measurement in Selenastrum capricornutum cells. The photosynthetic response was evaluated as a function of light intensity, cell concentration and initial dissolved oxygen. The inhibitory effect of some toxicants (1-butyl-3-methylimidazolium tetrafluoroborate, methanol) on dissolved oxygen production was also determined. In all cases, a toxic response was detected (i.e. a dose-related inhibition of photosynthetic activity was observed). For the present system, a time of only 2 h was needed to predict EC50 values as compared to 96 h for a conventional algal assay based on algal growth rate. Thus, the developed biosensor was proved to be useful as a rapid and simple test method in environmental toxicity assessment.

The ecotoxicity of ionic liquids and traditional organic solvents on microalga Selenastrum capricornutum.

In this study, the effects of several ionic liquids and traditional organic solvents on the growth of the green microalga, Selenastrum capricornutum, were investigated. The toxicities were strongly related to the incubation time and chemical structures of the ionic liquids. The toxicities of tetrabutylphosphonium and tetrabutylammonium containing bromide anion were observed to decrease when the incubation time was raised from 48 to 96 h. Conversely, the toxicities of 1-butyl-3-methylimidazolium and 1-butyl-3-methylpyridinium containing bromide anion were found to increase with increasing incubation time. Of the ionic liquids tested, 1-butyl-1-methylpyrrolidinium bromide was found to be the least toxic, which is similar in toxicity level of dimethylformamide. In general, the toxicities of the ionic liquids were estimated to be two and four orders of magnitude greater than those of the organic solvents examined, although ionic liquids are being considered as green solvents.

Toxicity of imidazolium salt with anion bromide to a phytoplankton Selenastrum capricornutum: effect of alkyl-chain length.

Room-temperature ionic liquids are regarded as environmentally benign alternatives to volatile organic solvents. However, the product designs for this promising group of compounds should take account, not only the technological needs, but also the eco-toxicological hazards. Therefore, this study aimed to evaluate the toxicity of some important ionic liquids on the growth of the freshwater alga, Selenastrum capricornutum. The ionic liquids examined in this study included 1-propyl-3-methylimidazolium [PMIM], 1-butyl-3-methylimidazolium [BMIM], 1-hexyl-3-methylimidazolium [HMIM] and 1-octyl-3-methylimidazolium [OMIM] with a bromide anion. The susceptibility of alga to ionic liquids was strongly dependent on the alkyl-chain length. According to our results, a longer alkyl-chain resulted in stronger inhibition of algal growth. In general, the toxicity could be summarized as decreasing in the following order: [OMIM]>[HMIM]>[BMIM]>or=[PMIM]. Among the ionic liquids examined, [OMIM] [Br] was found to be most toxic to S. capricornutum, with EC(50) values ranging from 26.3 microM to 54.9 microM after an incubating time of 96 h. Although [BMIM] [Br] and [PMIM] [Br] was relatively less toxic than [OMIM] and [HMIM], their toxicity increased as increasing the incubation time from 48 h to 96 h. This fact indicates that these kinds of ionic liquids may become more toxic after being released and contacted to freshwater ecosystem.