Iodinated X-ray Contrast Agents Research Articles

Bubble-less photocatalytic ozonation with ceramic membranes and static mixers enhances the total organic carbon removal and degradation of iodinated X-ray contrast agents

Conventional bubble-based ozonation of wastewater creates several issues, e.g., the low degradation of certain micropollutants like X-ray contrast agents, mass transfer limitations due to inhomogeneous mixing, and the waste of undissolved ozone. In contrast, this work uses tubular ceramic membranes for bubble-free and bubble-less ozonation. Static mixers are placed around the membrane to enhance the radial mixing of ozone, creating homogeneous reaction conditions throughout the membrane contactor. Additionally, the ozone mass transfer significantly increases with static mixers. Furthermore, the membrane is made of a photocatalyst (TiO2) on the shell-side to improve the micropollutant degradation by photocatalytic ozonation. An ozone-stable hydrophobic treatment method is developed to use ceramic membranes as a membrane contactor for the ozonation of water. After hydrophobic treatment, the ozone mass transfer coefficient is in the order of 1.3 ⋅ 10−6 ms−1 using bubble-less operation resulting in an ozone concentration up to 4.0 mg L−1. Overall, bubble-less operation significantly increases the ozone mass transfer compared to bubble-free operation. Photocatalytic ozonation in a membrane contactor with static mixers increases the degradation of diatrizoate by 37% compared to sole ozonation in the same membrane contactor. Furthermore, this process increases the removal of total organic carbon in experiments with a water matrix consisting of four different micropollutants by 115% compared to sole ozonation.

Antibacterial Effects of X-ray and MRI Contrast Media: An In Vitro Pilot Study.

Some radiological contrast agents have been shown to have effects on bacterial growth. In this study, the antibacterial effect and mechanism of action of iodinated X-ray contrast agents (Ultravist 370, Iopamiro 300, Telebrix Gastro 300 and Visipaque) and complexed lanthanide MRI contrast solutions (MultiHance and Dotarem) were tested against six different microorganisms. Bacteria with high and low concentrations were exposed to media containing different contrast media for various lengths of time and at pH 7.0 and 5.5. The antibacterial effect of the media was examined in further tests using agar disk diffusion analysis and the microdilution inhibition method. Bactericidal effects were found for microorganisms at low concentrations and low pH. Reductions were confirmed for Staphylococcus aureus and Escherichia coli.

Enhanced degradation of iohexol in water by CuFe2O4 activated peroxymonosulfate: Efficiency, mechanism and degradation pathway

Iohexol as an iodinated X-ray contrast agent is widely used, and it is the potential precursor for toxic iodinated disinfection by-products in the disinfection process. In this study, a series of CuFe2O4 catalysts were prepared by sol-gel method with different molar ratios of total metal cations to citric acid ([Men+]T/CA) and employed as heterogeneous catalysts to activate peroxymonosulfate (PMS) for the removal of iohexol. The catalysts were characterized by various technologies, and the effect of [Men+]T/CA molar ratio on the catalysts' properties was explored. The CuFe2O4 synthesized with [Men+]T/CA molar ratio of 1:1 showed the best catalytic activity to PMS, and 95.0% of 1.0 mg/L iohexol was removed within 15 min by using 50 mg/L CuFe2O4 and 20 mg/L PMS. The quenching experiment and electron spin resonance (ESR) spectra indicated the generation of SO4- and OH in the CuFe2O4/PMS system, and the quantity experiments revealed that the generation concentration of SO4- was ten times higher than that of OH. The generation mechanism of SO4- and ·OH were investigated by ATR-FTIR and X-ray photoelectron spectroscopy (XPS) spectra. The effects of catalyst dosage, PMS and iohexol concentration on the removal of iohexol were studied, and various water matrix factors including solution pH, natural organic matter (NOM) concentration and inorganic ions were also considered. Based on the twelve intermediate products of iohexol detected by UPLC-QTOF/MS, the degradation pathway was proposed. The high catalytic activity and reusability of CuFe2O4 indicated that CuFe2O4 activating PMS is an effective and sustainable way for the treatment of iohexol.

A nephroprotective iodinated contrast agent with cardioprotective properties: A pilot study.

Background and PurposeEvaluation and treatment of acute ischemic syndromes, in the heart and brain, require vessel visualization by iodinated X‐ray contrast agents. However, these contrast agents can induce injury, in both the kidneys and target organs themselves. Sulfobutylether beta cyclodextrin (SBECD) added to iohexol (SBECD‐iohexol) (Captisol Enabled‐iohexol, Ligand Pharmaceuticals, Inc, San Diego, CA) is currently in clinical trials in cardiovascular procedures, to determine its relative renal safety in high‐risk patients. Preclinical studies showed that SBECD‐iohexol reduced contrast‐induced acute kidney injury in rodent models by blocking apoptosis. The current study was undertaken to determine whether SBECD‐iohexol is also cardioprotective, in the male rat ischemia‐reperfusion model, compared to iohexol alone.MethodsAfter anesthesia, the left coronary artery was ligated for 30 min and the ligation released and reperfusion followed for 2 h prior to sacrifice. Groups 1–4 were injected in the tail vein 10 min prior to ischemia with: (1) vehicle; (2) iohexol; (3) SBECD; and (4) SBECD‐iohexol. Infarct size, hemodynamics, and serum markers were measured.ResultsAn eight‐fold increase in serum creatine kinase in the iohexol‐alone group was observed, compared with no increase in the SBECD‐iohexol group. The mean arterial pressure and rate pressure product were depressed in the iohexol‐alone group, but not in the SBECD‐iohexol group, or controls. No difference in infarct size or serum creatinine among the groups was observed.ConclusionThe results of this study suggest that SBECD‐iohexol is superior to iohexol alone, for both the preservation of cardiomyocyte integrity and preservation of myocardial function in myocardial ischemia.

Mechanochemistry Applied to the Synthesis of X-ray Contrast Agent

Mechanochemical activation in planetary ball mills generates energy that is effective for the efficient, solvent-free syntheses of several types of organic molecules, including active pharmaceutical ingredients and diagnostic agents. X-ray-based procedures are the most commonly used of all diagnostic imaging techniques, because they offer several advantages, such as deep penetration, high resolution, and low cost. Iodinated X-ray contrast agents have long been used in medicine to facilitate and improve the acquisition of images by radiographic modalities. Iopamidol was the first agent developed in the field of nonionic X-ray contrast agents for imaging diagnosis and is still one of the most frequently used worldwide. We herein report an experimental investigation aimed to design a mechanochemical synthesis of Iopamidol, with the double goals of process intensification and either the elimination or significant reduction of the use of the high-boiling-point and reprotoxic solvent N,N-dimethylacetamide. The greener wet milling protocol gave Iopamidol in higher yields using safer solvents such as acetonitrile and N,N-dimethyloctanamide.

The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water

The presence of iodinated X-ray contrast media (ICM) in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products (DBPs). The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron, OH were treated with five different ICMs, including iopamidol, iopromide, iohexol, diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs (iopromide, iohexol, diatrizoate, and iomeprol) expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water.

Automated thin-film microextraction coupled to a flow-through cell: somewhere in between passive and active sampling.

A prototype for the automated thin-film microextraction of pharmaceuticals from aqueous solutions has been developed and is presented here for the first time. With a software-controlled setup, extraction methods for ivermectin and iohexol have been developed. The widely used antiparasitic agent ivermectin is non-polar and has a high tendency to sorb to surfaces. In contrast to this, the nonionic but polar iodinated X-ray contrast agent iohexol is freely water soluble. With these two substances, a wide range of polarity is covered. Sorption kinetics and thermodynamics of ivermectin and iohexol were studied. With the presented passive sampling approach, it was possible to extract up to 96.2% ivermectin with a C18-phase within 1h and up to 74.6% of iohexol with a PS-DVB phase within 36h out of water. Using abamectin as internal standard, it was possible to quantitatively follow dissipation of ivermectin in a simulated surface water experiment. Predominantly, the newly developed prototype can be used for automated and time-resolved extraction of xenobiotics from waterbodies under field conditions, for the extraction of substances under laboratory conditions as an alternative to the elaborate solid-phase extraction, and for the automated control of chemical reaction kinetics.

Iodinated X-ray contrast agents: Photoinduced transformation and monitoring in surface water

Conventional wastewater treatment methods have shown to be unsuitable for a complete elimination of iodinated X-ray contrast agents (ICMs), which have thus been found in wastewater treatment plant (WWTP) effluent and in surface water. Once in the surface water, they could be transformed through different processes and form several transformation products that may need to be monitored as well. To this end, we studied the abatement and transformation of ICMs by combining laboratory experiments with in field analyses. We irradiated different aqueous solutions of the selected pollutants in the presence of TiO2 as photocatalyst, aimed to promote ICMs degradation and to generate photoinduced transformation products (TPs) similar to those occurring in the environment and effluent wastewater. This experimental strategy has been applied to the study of three ICMs, namely iopromide, iopamidol and diatrizoate. A total of twenty-four, ten, and ten TPs were detected from iopamidol, diatrizoate and iopromide, respectively. The analyses were performed using a liquid chromatography-LTQ-FT-Orbitrap mass spectrometer. The mineralization process and acute toxicity evolution were assessed as well over time and revealed a lack of mineralization for all ICMs and the formation of harmful byproducts.After characterizing these transformation products, WWTP effluent and surface water taken from several branches of the Chicago River were analyzed for ICMs and their TPs. HRMS with MS/MS fragmentation was used as a confirmatory step for proper identification of compounds in water and wastewater samples. All three of ICM were detected in the effluent and surface water samples, while no significant amount of TPs were detected.

Beyond TiO2: Cerium-Doped Zinc Oxide as a New Photocatalyst for the Photodegradation of Persistent Pollutants.

We prepared via hydrothermal synthesis zinc oxide samples doped with cerium. The samples were characterized via powder X Ray Diffraction measurements, Diffuse Reflectance UV Vis spectroscopy, Scanning Electron Microscopy and Transmission Electron Microscopy with EDX (Energy Dispersive X-Ray spectroscopy) analysis, and BET (Brunauer–Emmett–Teller) surface area analysis. XRD measurements reveal the formation of highly crystalline materials; wurtzite is the most important. All materials were tested using phenol as model molecule and their performances were compared with TiO2 P25. The material showing the best performance, namely Ce-doped ZnO, was then used to abate some emerging pollutants. We chose three iodinated X-ray contrast agent (ICM), iopromide, iopamidol and diatrizoate, known to be recalcitrant to traditional advanced oxidation processes. In the presence of TiO2 P25, all ICM exhibited a slow degradation, with t1/2 ranging from 30 min (iopamidol) to 120 min (diatrizoate) and several hours are required for their complete disappearance. The employment of Ce-doped ZnO leads to a sharp increase in their disappearance, with t1/2 obtained within 15 min (iopamidol) or 25 min (diatrizoate) and the complete abatement is achieved within 2 h.

Biodegradation of phenol, salicylic acid, benzenesulfonic acid, and iomeprol by Pseudomonas fluorescens in the capillary fringe

Mass transfer and biological transformation phenomena in the capillary fringe were studied using phenol, salicylic acid, benzenesulfonic acid, and the iodinated X-ray contrast agent iomeprol as model organic compounds and the microorganism strain Pseudomonas fluorescens. Three experimental approaches were used: Batch experiments (uniform water saturation and transport by diffusion), in static columns (with a gradient of water saturation and advective transport in the capillaries) and in a flow-through cell (with a gradient of water saturation and transport by horizontal and vertical flow: 2-dimension flow-through microcosm). The reactors employed for the experiments were filled with quartz sand of defined particle size distribution (dp=200…600μm, porosity ε=0.42). Batch experiments showed that phenol and salicylic acid have a high, whereas benzenesulfonic acid and iomeprol have a quite low potential for biodegradation under aerobic conditions and in a matrix nearly close to water saturation. Batch experiments under anoxic conditions with nitrate as electron acceptor revealed that the biodegradation of the model compounds was lower than under aerobic conditions. Nevertheless, the experiments showed that the moisture content was also responsible for an optimized transport in the liquid phase of a porous medium. Biodegradation in the capillary fringe was found to be influenced by both the moisture content and availability of the dissolved substrate, as seen in static column experiments. The gas–liquid mass transfer of oxygen also played an important role for the biological activity. In static column experiments under aerobic conditions, the highest biodegradation was found in the capillary fringe (e.g. βt/β0 (phenol)=0 after t=6 d) relative to the zone below the water table and unsaturated zone. The highest biodegradation occurred in the flow-through cell experiment where the height of the capillary fringe was largest.

Adverse skin reactions to iodinated x-ray contrast agents in healthy rats.

The aim of this preclinical study on healthy Sprague-Dawley rats was to determine whether differences exist in the induction of adverse skin reactions after the intravenous administration of a monomeric and 2 dimeric iodinated nonionic contrast agents. After intravenous injection of iopromide (monomeric), iodixanol (dimeric), and iotrolan (dimeric) at a dose of 4 g iodine/kg of body weight, mechanical ear volume measurements (10 minute after injection) and intravital microscopy (baseline, 5 minutes after injection) of the ear with the near-infrared dye indocyanine green were performed to determine the volume change and plasma extravasation. Histopathological analysis (20 minutes, 1 hour, and 3 hours after injection) was performed to diagnose alterations in the skin. Blood plasma was analyzed to identify elevated levels of histamine (5 minutes after injection) and inflammatory markers (a multianalyte profile of 58 markers; 1 hour and 3 hours after injection). Only iodixanol induced immediate angioedema formation, with a 100% incidence rate and with slight mast cell infiltration in the ear, muzzle, and paws. The ear showed a 53% volume increase and strong extravasation of plasma proteins into the interstitium, which correlated with highly (11-fold) increased plasma histamine levels 5 minutes after injection. Elevated levels of tumor necrosis factor-α (7.1-fold), macrophage inflammatory protein (MIP)-1α (3.2-fold), and MIP-2 (7.7-fold) were identified 1 hour after the iodixanol injection. Increased levels (fold-change) of MIP-1β (14; 6.3), monocyte chemotactic protein-1 (3.3; 3.7), monocyte chemotactic protein-3 (2.4; 3.0), stem cell factor (1.7; 2), vascular endothelial growth factor (2; 2.1), and interferon gamma-induced protein-10 (4.1; 39.1) were identified 1 hour and 3 hours after the iodixanol administration, respectively. The level of these molecules remained unchanged after the iopromide and iotrolan injections (except for stem cell factor). A reversible anaphylactoid-like reaction in healthy Sprague-Dawley rats was observed after the iodixanol administration but not after the monomeric iopromide or dimeric iotrolan injections. Therefore, we conclude that the induction of adverse skin reactions is not per se because of a class effect of dimeric contrast agent.

Utilization of nanoparticles as X‐ray contrast agents for diagnostic imaging applications

Among all the diagnostic imaging modalities, X-ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X-ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X-ray imaging. To date, clinically used X-ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X-ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X-rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X-ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X-ray contrast agents are discussed and the parameters that influence the efficacy of X-ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine-free NP-based X-ray contrast agents are then provided, emphasizing the studies performed to evaluate their X-ray attenuation capabilities and their toxicity in vitro and in vivo.

Study of the retention behavior of iodinated X-ray contrast agents in hydrophilic interaction liquid chromatography, comparing bare silica and zwitterionic stationary phases

Iodinated X-ray contrast media are the most widely used pharmaceuticals for intravascular administration in X-ray diagnostic procedures. The increasing concern of the fate of these compounds into the environment has led to the development of analytical methods to determine them. However, these methods present problems due to the polar character of these analytes. In this paper, hydrophilic interaction LC is presented as an alternative technique. The retention of iodinated X-ray contrast media was studied in two bare silica phases with different particle designs (i.e. porous and Fused Core™) and a zwitterionic sulfoalkylbetaine phase. The effect of the most important parameters of the mobile phase was studied for each stationary phase. It was observed that optimal mobile phase conditions included buffers with a high buffering capacity. Additionally, the retention mechanisms involved were studied in order to provide some insight into the possible occurring interactions. The contributions of partition and adsorption and the effect of the temperature on the retention of analytes were evaluated on all of the stationary phases.

Qualitative environmental risk assessment of photolytic transformation products of iodinated X-ray contrast agent diatrizoic acid

Recent studies have confirmed that the aquatic ecosystem is being polluted with an unknown cocktail of pharmaceuticals, their metabolites and/or their transformation products (TPs). Although individual chemicals are typically present at low concentrations, they can interact with each other resulting in additive or potentially even synergistic mixture effects. Therefore it is necessary to assess the environmental risk caused by these chemicals. Data on exposure is required for quantitative risk assessment of TPs and/or metabolites. Such data are mostly missing because of the non-availability of TPs and very often metabolites for experimental testing. This study demonstrates the application of different in silico tools for qualitative risk assessment using the example of photodegradation TPs (photo-TPs) of diatrizoic acid (DIAT), which itself is not readily biodegradable. Its photolytic transformation was studied and the photodegradation pathway was established. The aerobic biodegradability of photo-TPs under the conditions of an aquatic environment was assessed using standardized OECD tests. The qualitative risk assessment of DIAT and selected photo-TPs was performed by the PBT approach (i.e. Persistence, Bioaccumulation and Toxicity), using experimental biodegradation test assays, applying different QSAR models with several different toxicological endpoints and in silico read-across approaches. The qualitative risk assessment pointed out that the photo-TPs were less persistent compared to DIAT and none of them possessed any bioaccumulation threat. However, a few photo-TPs were predicted to be active for mutagenicity and genotoxicity, which indicate the need for further testing to confirm these predictions. The present study demonstrates that in silico qualitative risk assessment analysis can increase the knowledge space about the environmental fate of TPs.

Influence of different iodinated contrast media on the induction of DNA double‐strand breaks after in vitro X‐ray irradiation

The objective of this work was to examine differences in DNA double-strand break induction in peripheral blood lymphocytes after in vitro X-ray irradiation between iodinated contrast agents. Four different iodinated X-ray contrast agents--three of them with two different iodine concentrations--and mannitol (negative control; concentration of 150 mg mannitol per ml blood) were pipetted into blood samples so that there was a concentration of 0, 7.5 or 15 mg of iodine per ml blood in the samples. Negative controls without contrast medium (0 mg of iodine per ml blood) were also processed for every irradiation dose. The tubes were exposed to 0, 20 or 500 mGy in vitro X-ray irradiation. After that, the lymphocytes were separated by using density-gradient centrifugation. Fluorescence microscopy was applied to determine the average number of γH2AX-foci per lymphocyte in the presence or absence of different contrast media or mannitol. Differences in the number of γH2AX-foci were statistically analysed by one-way ANOVA and post-hoc Tukey's honestly significant difference test. Iodinated contrast agents led to a statistically significant increase in DNA double-strand breaks after in vitro irradiation. This effect increased statistically significant with rising radiation dose and appeared independent of the contrast agent used (iopromid, iodixanol, iomeprol, iopamidol). A statistically significant difference in DNA damage between the different tested contrast agents was not found. Therefore, the increase in DNA double-strand breaks depends solely on the amount of iodine applied. For evaluation of clinical consequences, our findings could be tested in further animal studies.

Determination of iodinated X-ray contrast agents in pharmaceutical formulations and artificial urine samples by differential pulse voltammetry

This manuscript shows how to quickly detect the concentration of three iodinated X-ray contrast agents (iopromide, iodixanol and amidotrizoic acid) using differential pulse voltammetry.

Dynamic Contrast-Enhanced Computed Tomography to Assess Antitumor Treatment Effects

Dynamic contrast-enhanced computed tomography (CT) is a sensitive method to evaluate functional changes of the tumor microvasculature after antitumor therapy by monitoring the kinetics of the contrast agent (CA) passage. Therefore, the pharmacokinetic properties of the CA possess a central role: iodinated x-ray CAs are small molecules that distribute rapidly within the extravascular extracellular space, whereas larger macromolecular compounds have a prolonged vascular phase and a restricted volume of distribution. The aim of this animal study was to compare the x-ray CA iopromide and the experimental gadolinium-based dendrimeric Gadomer in the assessment of early therapy response after a single dose of the novel multikinase inhibitor regorafenib. For the study, an experimental GS9L rat glioma model was used. For each CA, the animals were divided randomly into a therapy (n = 8) and a placebo group (n = 4). All animals underwent a baseline CT and a second examination 24 hours after therapy with regorafenib (10 mg/kg body weight, oral) and placebo, respectively. The CAs were administered intravenously at a dosage of 0.5 g I or Gd per kg body weight and dynamic CT scans (80 kV, 160 mAseff, no table feed) of the tumor region were performed up to 404 seconds post injection (p.i.). Image evaluation was done by analyzing tumor time-density curves, the area under the curve (AUC), and the results of the 2-compartment Patlak modeling. Significant differences in the time-density curves, the AUC, and the Patlak transfer constant (Ktrans) were observed 24 hours after the regorafenib therapy but not after the placebo treatment. The treatment effects visualized with iopromide were most pronounced at early time points (<100 seconds p.i.), whereas imaging with Gadomer was most effective at a later time window (300-404 seconds p.i.). Comparable reductions of the AUC to 0.69 ± 0.12 (iopromide) and 0.76 ± 0.11 (Gadomer) were found 24 hours after the therapy. A significant higher Ktrans was detected with iopromide (14.3 ± 2.7 mL per 100 mL/min) compared with Gadomer (1.8 ± 0.2 mL per 100 mL/min). However, the relative reduction in Ktrans to 67% ± 11% (iopromide) and to 68% ± 7% (Gadomer) 24 hours after the therapy was similar. Dynamic contrast-enhanced CT detects early treatment effects on tumor microvasculature after a single dose of regorafenib, independently of the used CA. Gadomer showed a later optimal imaging window than iopromide did. However, the efficacy of Gadomer- and iopromide-enhanced imaging is equivalent. The results demonstrate the potential of dynamic contrast-enhanced CT using clinically available x-ray CA in the assessment of early treatment response after administration of novel antitumor therapeutic agents.

EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents

In the year 2010, effluents from 90 European wastewater treatment plants (WWTPs) were analyzed for 156 polar organic chemical contaminants. The analyses were complemented by effect-based monitoring approaches aiming at estrogenicity and dioxin-like toxicity analyzed by in vitro reporter gene bioassays, and yeast and diatom culture acute toxicity optical bioassays. Analyses of organic substances were performed by solid-phase extraction (SPE) or liquid–liquid extraction (LLE) followed by liquid chromatography tandem mass spectrometry (LC-MS-MS) or gas chromatography high-resolution mass spectrometry (GC-HRMS). Target microcontaminants were pharmaceuticals and personal care products (PPCPs), veterinary (antibiotic) drugs, perfluoroalkyl substances (PFASs), organophosphate ester flame retardants, pesticides (and some metabolites), industrial chemicals such as benzotriazoles (corrosion inhibitors), iodinated x-ray contrast agents, and gadolinium magnetic resonance imaging agents; in addition biological endpoints were measured. The obtained results show the presence of 125 substances (80% of the target compounds) in European wastewater effluents, in concentrations ranging from low nanograms to milligrams per liter. These results allow for an estimation to be made of a European median level for the chemicals investigated in WWTP effluents. The most relevant compounds in the effluent waters with the highest median concentration levels were the artificial sweeteners acesulfame and sucralose, benzotriazoles (corrosion inhibitors), several organophosphate ester flame retardants and plasticizers (e.g. tris(2-chloroisopropyl)phosphate; TCPP), pharmaceutical compounds such as carbamazepine, tramadol, telmisartan, venlafaxine, irbesartan, fluconazole, oxazepam, fexofenadine, diclofenac, citalopram, codeine, bisoprolol, eprosartan, the antibiotics trimethoprim, ciprofloxacine, sulfamethoxazole, and clindamycine, the insect repellent N,N′-diethyltoluamide (DEET), the pesticides MCPA and mecoprop, perfluoroalkyl substances (such as PFOS and PFOA), caffeine, and gadolinium.

A novel approach for the direct determination of residual template molecules in molecularly imprinted polymer matrices

With inductively coupled plasma optical emission spectroscopy (ICP-OES), this article introduces an analysis method enabling the direct quantitative determination of residual template molecules in molecularly imprinted polymer (MIP) matrices. ICP-OES was applied for the determination of residual iodine in MIPs prepared against the iodinated X-ray contrast agent iohexol. Prior to analysis, a microwave-assisted acidic oxidative digestion method was developed simultaneously enabling the digestion of the polymer matrix and the exhaustive oxidation of organically bound iodine. Excellent recovery rates and a high accuracy confirm the feasibility and utility of a microwave-assisted digestion with subsequent ICP-OES analysis for the determination of residual iodine in MIPs, and indicate the potential of this combination as a widely applicable monitoring tool for the efficiency of template extraction from MIP matrices.

The presence of iodinated contrast agents amplifies DNA radiation damage in computed tomography

The purpose of this study was to determine the influence of iodinated contrast agents on the formation of DNA double-strand breaks in vitro in lymphocytes and to verify these results in patients undergoing diagnostic computed tomography examinations. Blood samples were irradiated in vitro in the presence of iodinated X-ray contrast agent. Controls were irradiated without contrast agent. Fourteen patients were investigated using contrast-enhanced computed tomography (CT), and 14 other patients with unenhanced CT. Blood samples were taken prior to and 5 min and 1, 2 and 24 h after the CT examination. In these blood samples the average number of γH2Ax-foci per lymphocyte was enumerated by fluorescence microscopy. Statistical differences between foci numbers developed in the presence and absence of contrast agent were tested using an independent sample t-test. In vitro foci numbers after irradiation were significantly higher when contrast agent was present during irradiation. In vivo, γH2Ax-foci levels were 58% higher in patients undergoing contrast-enhanced CT compared with those undergoing unenhanced CT. In the presence of iodinated contrast agents DNA, damage is increased and the radiation dose is not the only factor affecting the amount of DNA damage. Individual patient characteristics and biological dosimetry applications, e.g. the analysis of γH2Ax-foci, have to be considered.