Phosphonium-based ionic liquids as modifiers for biomedical grade poly(vinyl chloride).

This work reports and discusses the influence of four phosphonium-based ionic liquids (PhILs), namely trihexyl(tetradecyl) phosphonium dicyanamide, [P(6,6,6,14)][dca]; trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, [P(6,6,6,14)][Tf(2)N]; tetrabutyl phosphonium bromide, [P(4,4,4,4)][Br]; and tetrabutyl phosphonium chloride, [P(4,4,4,4)][Cl], on some of the chemical, physical and biological properties of a biomedical-grade suspension of poly(vinyl chloride) (PVC). The main goal of this work was to evaluate the capacity of these PhILs to modify some of the properties of neat PVC, in particular those that may allow their use as potential alternatives to traditional phthalate-based plasticizers in PVC biomedical applications. PVC films having different PhIL compositions (0, 5, 10 and 20 wt.%) were prepared (by solvent film casting) and characterised by Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, dynamical mechanical thermal analysis, scanning electron microscopy/energy-dispersive X-ray/electron probe microanalysis, X-ray diffraction, transmittance, permeability towards oxygen and carbon dioxide, thermal degradation, contact angle measurement, water and vapour uptake, leachability and biocompatibility (haemolytic potential, thrombogenicity and cytotoxicity). A conventional organic plasticizer (di-isononyl phthalate) was used for comparison purposes. The results obtained showed that it was possible to change the neat PVC hydrophobicity, and consequently its water uptake capacity and plasticizer leachability, just by changing the PhIL employed and its composition. It was also possible to significantly change the thermal and mechanical properties of PVC films by choosing appropriate PhIL cation/anion combinations. However, a specific PhIL may not always be capable of simultaneously keeping and/or improving both physical properties. In addition, ionic halide salts were found to promote PVC dehydrochlorination. Finally, none of the prepared materials presented toxicity against Caco-2 cells, though pure [P(6,6,6,14)][dca] decreased HepG2 cells viability. Moreover, PVC films with [P(6,6,6,14)][dca] and [P(4,4,4,4)][Cl] were found to be haemolytic and thus these PhILs must be avoided as PVC modifiers if biomedical applications are envisaged. In conclusion, from all the PhILs tested, [P(6,6,6,14)][Tf(2)N] showed the most promising results regarding blood compatibility, leaching and permeability to gases of PVC films. The results presented are a strong indicator that adequate PhILs may be successfully employed as PVC multi-functional plasticizers for a wide range of potential applications, including those in the biomedical field.

Nickel response in function of temperature differences: effects at different levels of biological organization in Daphnia magna.

In this study, gene transcription profiling in combination with the assessment of systemic parameters at individual and population levels were applied to study the (toxic) effects induced through temperature stress in the presence or the absence of an additional chemical stressor (nickel) in Daphnia magna. It was illustrated that lower temperatures were mainly characterized by a reduction of growth and lipid content, while higher temperatures caused an increase of both endpoints. Many of the differentially regulated transcripts could be correlated with processes affected at higher hierarchical levels of biological organization. Gene clusters with probable roles in producing offspring (peak expression at 22°C), enhancing the metabolic rate (temperature related expression) and translational processes (increased expression at 14°C) were identified. However, it was not possible to pinpoint a specific subset of genes, exclusively responding to temperature or nickel and allowing a retrospective identification of the particular stressor. Overall, extreme temperatures caused a higher level of stress in the organisms in comparison to nickel exposure. Moreover, organisms subjected to the natural stressor appeared to be less capable of dealing with the additional chemical stressor and as a result activate or repress more gene pathways.

Is ultraviolet radiation a synergistic stressor in combined exposures? The case study of Daphnia magna exposure to UV and carbendazim.

The toxicological assessment of chemical compounds released to the environment is more accurate when mixtures of chemicals and/or interactions between chemicals and natural stressors are considered. Ultraviolet radiation can be taken as a natural stressor since the levels of UV are increasing due to the decrease of its natural filter, the stratospheric ozone concentration. Therefore, a combination of chemical exposures and increasing UV irradiance in aquatic environments is likely to occur. In the current study, combined effects of carbendazim and ultraviolet radiation were evaluated, using selected life traits as endpoints on Daphnia magna. To design combined exposures, first single chemical and natural stressor bioassays were performed: a reproduction test with carbendazim and a reproduction, feeding inhibition and Energy budget test with ultraviolet radiation. Following single exposures, the combinations of stressors included exposures to UV radiation and carbendazim for a maximum exposure time of 4h, followed by a post-exposure period in chemically contaminated medium for a maximum of 15 days, depending on the endpoint, where the effects of the combined exposures were investigated. Statistical analyses of the data set were performed using the MixTox tool and were based on the conceptual model of Independent Action (IA) and possible deviations to synergism or antagonism, dose-ratio or dose-level response pattern. Both ultraviolet radiation and carbendazim as single stressors had negative impacts on the measured life traits of daphnids, a decrease on both feeding rates and reproduction was observed. Feeding rates and reproduction of D. magna submitted to combined exposures of ultraviolet radiation and carbendazim showed a dose-ratio deviation from the conceptual model as the best description of the data set, for both endpoints. For feeding inhibition, antagonism was observed when the UV radiation was the dominant item in combination, and for reproduction, synergism was observed when UV radiation dominated the exposure. From these results, the combined exposure of ultraviolet radiation and chemical compounds should also be considered for risk assessment as this study has shown that more severe effect than expected by single chemical assessment might be observed.

The influence of natural stressors on the toxicity of nickel to Daphnia magna.

Global warming has become a source of awareness regarding the potential deleterious effects of extreme abiotic factors (e.g., temperature, dissolved oxygen (DO) levels) and also their influence on chemicals toxicity. In this work, we studied the combined effects of nickel and temperature (low and high levels) and nickel and low levels of DO to Daphnia magna, and concentration addition and independent action concepts as well as their deviations for synergism/antagonism, dose ratio and dose level dependency, were applied to survival and feeding rate data. Nickel single exposure showed an LC(50) value for 48 h of 7.36 mg l(-1) and an EC(50) value for feeding impairment at 2.41 mg l(-1). In the acute exposures to high and low temperatures, 50% of mortality was observed, respectively, at 30.7 degrees C and 4.2 degrees C whereas 50% reduction on the feeding activity was recorded at 22.6 degrees C and 16.0 degrees C. Relatively to low DO levels, a LC(50) value for 48 h of 0.5 mg l(-1) was obtained; feeding activity EC(50) value was 2 mg l(-1). On acute combined experiments, antagonism was observed for the combination of nickel and extreme temperatures, whereas a synergistic behaviour was observed in the combined exposure of nickel and low DO levels. At sublethal levels, nickel showed to be the main inducer of toxicity at high and low temperatures but not at low levels of dissolved oxygen. Toxicokinetics and toxicodynamics modelling studies should be made in the future to understand the toxicological pathways involved on complex combinations of stressors and to validate any conclusions.

Toxicity prediction of binary combinations of cadmium, carbendazim and low dissolved oxygen on Daphnia magna.

Environmental contamination is often characterised by a combination of stress factors of various sources (biological, physical and chemical). The predictability of their joint effects is an important stage in environmental risk assessment procedures. In this study, the two main conceptual models for mixture evaluation based on the effect of individual compounds, concentration addition (CA) and independent action (IA) and deviations to synergism/antagonism, "dose ratio" and "dose level" dependency were used. The single and combined effects of cadmium, carbendazim and low dissolved oxygen levels were assayed for life-cycle parameters (survival and feeding) of the water flea Daphnia magna Straus. The results of single exposures revealed an increase of acute and chronic toxicity as concentrations of cadmium and carbendazim increases. At low dissolved oxygen levels both survival and feeding parameters were significantly affected (P< or =0.05). In the acute mixture exposure of cadmium and carbendazim a "dose ratio" dependency was observed with a higher toxicity when cadmium was dominant whereas at high concentrations of carbendazim a lower effect on survival was observed. At chronic exposures an antagonistic deviation from IA model was observed for this mixture. The IA model showed to be adequate for toxicity prediction on acute exposure combinations with low DO levels where a synergistic behaviour was observed. However, at sublethal exposures IA and CA models failed by underestimation. Validation from toxicokinetic and toxicodynamic modelling studies should be made in the future as a way to understand toxicological pathways involved in complex mixture/combination exposures.