Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Evaluation of the accumulation of the iodinated contrast agents diatrizoic acid and iohexol in Dreissena polymorpha mollusks.

Mollusks are very sensitive to aquatic environmental alterations and then, are important bio-indicators for monitoring the contamination of water bodies. Iodinated X-ray contrast media (ICMs) are ubiquitously present in the aquatic environment, primarily due to their high consumption for diagnosis purposes, high injection levels, low biodegradability, and low removal rates by wastewater treatment plants. Although these compounds are assumed to be of low toxicity, aquatic organisms are continuously exposed to these agents, which may result in adverse effects as ICMs can act as iodine source and disrupt the endocrine system. Thus, the evaluation of their environmental risk, especially on aquatic fauna is of great interest. To this end, we first compared the accumulation behavior, based on iodine analysis, of two ICM exhibiting different osmolality, diatrizoic acid and iohexol in Dreissena polymorpha bivalves exposed under laboratory conditions at concentrations of 0, 100, and 1000 µg/L during 4 and 7 days. This study was the first to provide information on iodine concentration in whole soft tissues and several organs in control zebra mussels. Moreover, it showed, after exposure, an increase of iodine content mainly in the digestive glands, followed by gills and gonads, highlighting that ICMs actually enter the organisms. Thus, bioaccumulation of ICMs studies were then performed, by liquid chromatography coupled to tandem mass spectrometry, on entire mollusks and digestive glands of organisms exposed at 0, 10, 100, and 1000 µg/L of both ICMs during 21 days, followed by 4 days of depuration. These first data on ICMs concentrations in zebra mussels, showed a clear accumulation of ICMs in mussels as a function of relative exposure level, as well as a rapid depuration. Osmolality did not seem to have a significant impact on the accumulation level, but a slight difference was observed on the accumulation pattern between both ICMs.

Assessing the skin irritation and sensitizing potential of concentrates of water chlorinated in the presence of iodinated X-ray contrast media.

Chemical disinfection of water provides significant public health benefits. However, disinfectants like chlorine can react with naturally occurring materials in the water to form disinfection byproducts (DBPs). Natural levels of iodine have been reported to be too low in some source waters to account for the levels of iodinated DBPs detected. Iodinated X-ray contrast media (ICM) have been identified as a potential source of iodine. The toxicological impact of ICM present in source water at the time of disinfection has not been fully investigated. Iopamidol, iohexol, iopromide, and diatrizoate are among the ICM most frequently detected in water. In this study, source water containing one of these four ICM was chlorinated; non-chlorinated ICM-containing water samples served as controls. Reactions were conducted at an ICM concentration of 5 µM and a chlorine dose of 100 µM over 72 hr. Water concentrates (20,000-fold) were prepared by XAD-resin/ethyl acetate extraction and DMSO solvent exchange. We used the MatTek® reconstituted human epithelial skin irritation model to evaluate the water concentrates and also assessed the dermal irritation and sensitization potential of these concentrates using the LLNA:BrdU ELISA in BALB/c mice. None of the water concentrates tested (2500X) resulted in a skin irritant response in the MatTek® skin irritation model. Likewise, none of the concentrates (2500X, 1250X, 625X, 312.5X, 156.25X) produced a skin irritation response in mice: erythema was minimal; the maximum increase in ear thickness was less than 25%. Importantly, none of the concentrates produced a positive threshold response for allergic skin sensitization at any concentration tested in the LLNA:BrdU ELISA. We conclude that concentrates of water disinfected in the presence of four different ICM did not cause significant skin irritation or effects consistent with skin sensitization at the concentrations tested.

A direct injection liquid chromatography tandem mass spectrometry method for the kinetic study on iodinated contrast media (ICMs) removal in natural water.

Iodinated contrast media (ICMs) are a class of X-ray contrast media worldwide utilized for radiographic procedures. Since they cannot be removed efficiently during water treatment, they can be found in surface and groundwater. In this work, a rapid and sensitive direct injection liquid chromatography-tandem (LC-MS/MS) method for the simultaneous analysis of seven ICMs media (iopamidol, ioxitalamic acid, diatrizoic acid, iothalamic acid, iohexol, iomeprol and iopromide) in complex aqueous matrices has been developed and validated. The MDLs for the analytes ranged from 0.7 to 21 ng L-1 in ultrapure water, and recoveries ranged from 86 to 100% in drinking water, 85-103% in groundwater and 84-105% in WWTP effluent. A stereo-isomer for iopromide was separated. This analytic method was applied to investigate the removal of target ICMs by low pressure ultra violet light (LPUV) advanced oxidation processes with three oxidants, hydrogen peroxide, free chlorine and monochloramine in groundwater. Results showed that the addition of oxidants did not enhance attenuation of ICMs, since fluence-based decay apparent rate constants were similar (KUV = 3.2 × 10-3, KUV-Cl2 = 3.6 × 10-3 and KUV-NH2 = 3.4 × 10-3 10-3 cm2 mJ-1). This yielded direct photolysis is the main mechanism to attenuate target ICMs.

Detection of artificial sweeteners and iodinated X-ray contrast media in wastewater via LC-MS/MS and their potential use as anthropogenic tracers in flowing waters.

The detection of wastewater impact on stream chemistry is often hindered by high background concentrations of ubiquitous solutes. In the present study we tested the applicability of artificial sweeteners (AS) and iodinated X-ray contrast media (ICM) as tracers to detect this impact by examining wastewater treatment plant (WWTP) effluents and surface water samples. The developed direct injection LC-MS/MS method enabled the detection of these anthropogenic micropollutants in aqueous samples down to trace level concentrations. The 2-h-composite sampling of WWTP effluent revealed fluctuating ICM concentrations between and within days with highest concentrations at the end of the week. Diatrizoic acid (DTZ) and iopromide (IOP) were the predominant ICM with concentrations up to 7 µg/L. Concentrations of the AS acesulfame (ACE) fluctuated between 0.5 µg/L and 1 µg/L. Concentrations of AS and ICM in surface water were both associated with wastewater impact. DTZ contamination was more widespread whereas some sampling points exhibited a more pronounced contamination with non-ionic ICM. Surface water was frequently contaminated with AS. Particularly ACE was detected in every surface water sample indicating that it is chemically stable and that inputs to the aquatic environment via WWTP effluents are widespread. The broad application of ACE as food additive enables its application as a tracer throughout Germany. Furthermore, the developed LC-MS/MS method enables rapid detection of ACE down to the low ng/L-range. Nonetheless, DTZ or IOP could be used in addition to ACE to verify anthropogenic influences on natural waters.

A New Platform for Profiling Degradation-Related Impurities Via Exploiting the Opportunities Offered by Ion-Selective Electrodes: Determination of Both Diatrizoate Sodium and Its Cytotoxic Degradation Product.

Although the ultimate goal of administering active pharmaceutical ingredients (APIs) is to save countless lives, the presence of impurities and/or degradation products in APIs or formulations may cause harmful physiological effects. Today, impurity profiling (i.e., the identity as well as the quantity of impurity in a pharmaceutical) is receiving critical attention from regulatory authorities. Despite the predominant use of spectroscopic and chromatographic methods over electrochemical methods for impurity profiling of APIs, this work investigates the opportunities offered by electroanalytical methods, particularly, ion-selective electrodes (ISEs), for profiling degradation-related impurities (DRIs) compared with conventional spectroscopic and chromatographic methods. For a meaningful comparison, diatrizoate sodium (DTA) was chosen as the anionic X-ray contrast agent based on its susceptibility to deacetylation into its cytotoxic and mutagenic degradation product, 3,5-diamino-2,4,6 triiodobenzoic acid (DTB). This cationic diamino compound can be also detected as an impurity in the final product because it is used as a synthetic precursor for the synthesis of DTA. In this study, four novel sensitive and selective sensors for the determination of both DTA and its cytotoxic degradation products are presented. Sensors I and II were developed for the determination of the anionic drug, DTA, and sensors III and IV were developed for the determination of the cationic cytotoxic impurity. The use of these novel sensors not only provides a stability-indicating method for the selective determination of DTA in the presence of its degradation product, but also permits DRI profiling. Moreover, a great advantage of these proposed ISE systems is their higher sensitivity for the quantification of DTB relative to other spectroscopic and chromatographic methods, so it can measure trace amounts of DTB impurities in DTA bulk powder and pharmaceutical formulation without a need for preliminary separation.

Monitoring of the degradation kinetics of diatrizoate sodium to its cytotoxic degradant using a stability-indicating high-performance liquid chromatographic method.

The X-ray diagnostic agent sodium diatrizoate (DTA) was studied for chemical degradation. The 3,5-diamino derivative was found to be the alkaline and acidic degradation product. The 3,5-diamino degradate is also the synthetic precursor of DTA and it is proved to have cytotoxic and mutagenic effects. A sensitive, selective and precise high-performance liquid chromatographic stability-indicating method for the determination of DTA in the presence of its acidic degradation product and in pharmaceutical formulation was developed and validated. Owing to the high toxicity of the degradation product, the kinetics of the acidic degradation process was monitored by the developed RP-HPLC method. The reaction was found to follow pseudo-first order kinetics. The kinetic parameters such as rate constant (K) and half-life (t½ ) were calculated under different temperatures and acid concentrations; activation energy was estimated from the Arrhenius plot. The developed RP-HPLC method depends on isocratic elution of a mobile phase composed of methanol-water (25:75 v/v; pH adjusted with phosphoric acid), and UV detection at 238 nm. The method showed good linearity over a concentration range of 2-100 µg/mL with mean percentage recovery of 100.04 ± 1.07. The selectivity of the proposed method was tested using laboratory-prepared mixtures. The proposed method has been successfully applied to the analysis of DTA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with the official USP method. Validation of the proposed method was performed according to International Conference on Harmonization guidelines.

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.

Degradation of the long-resistant pharmaceutical compounds carbamazepine and diatrizoate using mixed microbial culture.

The microbial degradation of two recalcitrant pharmaceutical compounds, carbamazepine (CBZ) and diatrizoate (DTZ), was studied in laboratory batch experiments. We used a defined mixed microbial culture comprising four distinct microbial species that were previously known to have high decomposition capacity toward recalcitrant substances. Biological decomposition in liquid phase cultures for either CBZ or DTZ, or in a combination of the two, was conducted for 12 days. DTZ and CBZ were degraded by 43.2% and 60%, respectively from an initial concentration of 100 µg L(-1). When degradation was assessed using a mixture of the two compounds, the initial degradation rates of CBZ and DTZ were lower than those observed in the single-compound study. However, the final cumulative removal efficiency was very similar. The extent of dissolved organic carbon (DOC) removal was correlated with the degradation of the pharmaceuticals.

Overall adsorption rate of metronidazole, dimetridazole and diatrizoate on activated carbons prepared from coffee residues and almond shells.

This study analyzed the overall adsorption rate of metronidazole, dimetridazole, and diatrizoate on activated carbons prepared from coffee residues and almond shells. It was also elucidated whether the overall adsorption rate was controlled by reaction on the adsorbent surface or by intraparticle diffusion. Experimental data of the pollutant concentration decay curves as a function of contact time were interpreted by kinetics (first- and second-order) and diffusion models, considering external mass transfer, surface and/or pore volume diffusion, and adsorption on an active site. The experimental data were better interpreted by a first-order than second-order kinetic model, and the first-order adsorption rate constant varied linearly with respect to the surface area and total pore volume of the adsorbents. According to the diffusion model, the overall adsorption rate is governed by intraparticle diffusion, and surface diffusion is the main mechanism controlling the intraparticle diffusion, representing >90% of total intraparticle diffusion.

Stability indicating spectrophotometric and spectrodensitometric methods for the determination of diatrizoate sodium in presence of its degradation product.

Three sensitive, selective, and precise stability indicating methods for the determination of the X-ray contrast agent, diatrizoate sodium (DTA), in the presence of its acidic degradation product (highly cytotoxic 3,5 diamino metabolite) and in pharmaceutical formulation were developed and validated. The first method is a first derivative (D1) spectrophotometric one, which allows the determination of DTA in the presence of its degradate at 231.2 nm (corresponding to zero crossing of the degradate) over a concentration range of 2-24 µg/mL with mean percentage recovery 99.95±0.97%. The second method is the first derivative of the ratio spectra (DD1) by measuring the peak amplitude at 227 nm over the same concentration range as D1 spectrophotometric method, with mean percentage recovery 99.99±1.15%. The third method is a TLC-densitometric one, where DTA was separated from its degradate on silica gel plates using chloroform:methanol:ammonium hydroxide (20:10:2 by volume) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of DTA at 238 nm over a concentration range of 4-20 µg/spot, with mean percentage recovery 99.88±0.89%. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DTA in pharmaceutical dosage forms without interference from other dosage form additives. The results were statistically compared with the official US pharmacopeial method. No significant difference for either accuracy or precision was observed.

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.

Removal of the X-ray contrast media diatrizoate by electrochemical reduction and oxidation.

Due to their resistance to biological wastewater treatment, iodinated X-ray contrast media (ICM) have been detected in municipal wastewater effluents at relatively high concentrations (i.e., up to 100 µg L(-1)), with hospitals serving as their main source. To provide a new approach for reducing the concentrations of ICMs in wastewater, electrochemical reduction at three-dimensional graphite felt and graphite felt doped with palladium nanoparticles was examined as a means for deiodination of the common ICM diatrizoate. The presence of palladium nanoparticles significantly enhanced the removal of diatrizoate and enabled its complete deiodination to 3,5-diacetamidobenzoic acid. When the system was employed in the treatment of hospital wastewater, diatrizoate was reduced, but the extent of electrochemical reduction decreased as a result of competing reactions with solutes in the matrix. Following electrochemical reduction of diatrizoate to 3,5-diacetamidobenzoic acid, electrochemical oxidation with boron-doped diamond (BDD) anodes was employed. 3,5-Diacetamidobenzoic acid disappeared from solution at a rate that was similar to that of diatrizoate, but it was more readily mineralized than the parent compound. When electrochemical reduction and oxidation were coupled in a three-compartment reactor operated in a continuous mode, complete deiodination of diatrizoate was achieved at an applied cathode potential of -1.7 V vs SHE, with the released iodide ions electrodialyzed in a central compartment with 80% efficiency. The resulting BDD anode potential (i.e., +3.4-3.5 V vs SHE) enabled efficient oxidation of the products of the reductive step. The presence of other anions (e.g., chloride) was likely responsible for a decrease in I(-) separation efficiency when hospital wastewater was treated. Reductive deiodination combined with oxidative degradation provides benefits over oxidative treatment methods because it does not produce stable iodinated intermediates. Nevertheless, the process must be further optimized for the conditions encountered in hospital wastewater to improve the separation efficiency of halide ions prior to the electrooxidation step.

Trace detection of meglumine and diatrizoate from Bacillus spore samples using liquid chromatography/mass spectrometry.

Following the September 11, 2001 terrorist attacks, letters containing Bacillus anthracis were distributed through the United States postal system killing five people. A complex forensic investigation commenced to identify the perpetrator of these mailings. A novel liquid chromatography/mass spectrometry protocol for the qualitative detection of trace levels of meglumine and diatrizoate in dried spore preparations of B. anthracis was developed. Meglumine and diatrizoate are components of radiographic imaging products that have been used to purify bacterial spores. Two separate chromatographic assays using multiple mass spectrometric analyses were developed for the detection of meglumine and diatrizoate. The assays achieved limits of detection for meglumine and diatrizoate of 1.00 and 10.0 ng/mL, respectively. Bacillus cereus T strain spores were effectively used as a surrogate for B. anthracis spores during method development and validation. This protocol was successfully applied to limited evidentiary B. anthracis spore material, providing probative information to the investigators.

Biogenic palladium enhances diatrizoate removal from hospital wastewater in a microbial electrolysis cell.

To decrease the load of pharmaceuticals to the environment, decentralized wastewater treatment has been proposed for important point-sources such as hospitals. In this study, a microbial electrolysis cell (MEC) was used for the dehalogenation of the iodinated X-ray contrast medium diatrizoate. The presence of biogenic palladium nanoparticles (bio-Pd) in the cathode significantly enhanced diatrizoate removal by direct electrochemical reduction and by reductive catalysis using the H(2) gas produced at the cathode of the MEC. Complete deiodination of 3.3 µM (2 mg L(-1)) diatrizoate from a synthetic medium was achieved after 24 h of recirculation at an applied voltage of -0.4 V. An equimolar amount of the deiodinated metabolite 3,5-diacetamidobenzoate (DAB) was detected. Higher cell voltages increased the dehalogenation rates, resulting in a complete removal after 2 h at -0.8 V. At this cell voltage, the MEC was also able to remove 85% of diatrizoate from hospital effluent containing 0.5 µM (292 µg L(-1)), after 24 h of recirculation. Complete removal was obtained when the effluent was continuously fed at a volumetric loading rate of 204 mg diatrizoate m(-3) total cathodic compartment (TCC) day(-1) to the MEC with a hydraulic retention time of 8 h. At -0.8 V, the MEC system could also eliminate 54% of diatrizoate from spiked urine during a 24 h recirculation experiment. The final product DAB was demonstrated to be removable by nitrifying biomass, which suggests that the combination of a MEC and bio-Pd in its cathode offers potential to dehalogenate pharmaceuticals, and to significantly lower the environmental burden of hospital waste streams.

Degradation mechanisms and kinetic studies for the treatment of X-ray contrast media compounds by advanced oxidation/reduction processes.

The presence of iodinated X-ray contrast media compounds (ICM) in surface and ground waters has been reported. This is likely due to their biological inertness and incomplete removal in wastewater treatment processes. The present study reports partial degradation mechanisms based on elucidating the structures of major reaction by-products using gamma-irradiation and LC-MS. Studies conducted at concentrations higher than observed in natural waters is necessary to elucidate the reaction by-product structures and to develop destruction mechanisms. To support these mechanistic studies, the bimolecular rate constants for the reaction of OH and e(-)(aq) with one ionic ICM (diatrizoate), four non-ionic ICM (iohexol, iopromide, iopamidol, and iomeprol), and the several analogues of diatrizoate were determined. The absolute bimolecular reaction rate constants for diatrizoate, iohexol, iopromide, iopamidol, and iomeprol with OH were (9.58 +/- 0.23)x10(8), (3.20 +/- 0.13)x10(9), (3.34 +/- 0.14)x10(9), (3.42 +/- 0.28)x10(9), and (2.03 +/- 0.13) x 10(9) M(-1) s(-1), and with e(-)(aq) were (2.13 +/- 0.03)x10(10), (3.35 +/- 0.03)x10(10), (3.25 +/- 0.05)x10(10), (3.37 +/- 0.05)x10(10), and (3.47 +/- 0.02) x 10(10) M(-1) s(-1), respectively. Transient spectra for the intermediates formed by the reaction of OH were also measured over the time period of 1-100 micros to better understand the stability of the radicals and for evaluation of reaction rate constants. Degradation efficiencies for the OH and e(-)(aq) reactions with the five ICM were determined using steady-state gamma-radiolysis. Collectively, these data will form the basis of kinetic models for application of advanced oxidation/reduction processes for treating water containing these compounds.

Rapid analysis of iodinated X-ray contrast media in secondary and tertiary treated wastewater by direct injection liquid chromatography-tandem mass spectrometry.

The iodinated X-ray contrast media are the most widely administered intravascular pharmaceuticals and are known to persist in the aquatic environment. A rapid method using direct injection liquid chromatography-tandem mass spectrometry (DI-LC-MS/MS) has been developed to measure eight ICM. These include iopamidol, iothalamic acid, diatrizoic acid, iohexol, iomeprol, iopromide, plus both ioxaglic acid and iodipamide, which have not previously reported in the literature. The LC-MS/MS fragmentation patterns obtained for each of the compounds are discussed and the fragments lost for each transition are identified. Matrix effects in post-RO water, MQ water, tap water and secondary effluent have also been investigated. The DI-LC-MS/MS method was validated on both secondary and tertiary treated wastewater, and applied to samples from an advanced activated sludge wastewater treatment plant (WWTP) and a water recycling facility using microfiltration (MF) and reverse osmosis (RO) in Perth, Western Australia. As well as providing information of the efficacy for RO to remove specific ICM, these results also represent the first values of ICM published in the literature for Australia.

Monitoring of iodinated X-ray contrast media in surface water.

A monitoring programme was carried out in order to determine iodinated X-ray contrast media (ICM) in the River Danube and to investigate the raw water quality for drinking water production at Langenau waterworks. The study revealed that the maximum concentrations of ICM (over 500 ng l(-1) for diatrizoic acid and iopamidol) were found in 2h-composite samples taken from the downstream of the Ulm/Neu-Ulm metropolitan area. By means of a concentration profile over one month the highest ICM concentrations were observed on weekdays. The extended data evaluation with principal component analysis shows that the upstream and downstream samples had different pattern of variations in ICM concentration and also demonstrates a clear change in ICM composition by the discharge of municipal wastewater. In addition to load profiles of ICM, time-dependent plots of principal component 1 exhibited peaks, indicating a short-term discharge of ICM between the two sampling sites. In conclusion, a point source for ICM contamination between the sampling sites in Ulm upstream and Leipheim downstream seems to be the reasonable explanation for peak ICM concentrations. Due to the observed high variations of ICM concentrations in river, the evaluation of natural waters by means of a single analysis is not representative.

Biodegradability of the X-ray contrast compound diatrizoic acid, identification of aerobic degradation products and effects against sewage sludge micro-organisms.

Pharmaceuticals and contrast media have been detected in hospital effluents, sewage treatment plants, surface water, and ground water. Only little is known about their elimination during sewage treatment and effects of possible biotransformation products against bacteria. The modified Zahn-Wellens test (ZWT, OECD 302 B) and a test simulating biological sewage treatment (modified OECD 303 A test) were used to assess the biodegradability of the widely used ionic iodinated contrast agent diatrizoic acid (diatrizoate). Effects against sewage sludge bacteria were studied in the two test systems by monitoring the biomarkers quinones, polyamines, phospholipids and adenosine triphosphate. Diatrizoate was biotransformed into 2,4,6-triiodo-3,5-diamino-benzoic acid in the ZWT. 2,4,6-Triiodo-3,5-diamino-benzoic acid was stable under the test conditions of the ZWT. Diatrizoate was not eliminated in the OECD 303 A simulation test. It was not adsorbed by the sewage sludge. No effects of the test compound or its aerobic transformation products against the bacteria present in the sewage sludge were detected using phospholipids, quinones, polyamines, and adenosine triphosphate as biomarkers.

Occurrence of triiodinated X-ray contrast agents in the aquatic environment.

High concentrations of adsorbable organic iodine (AOI) are found in municipal treatment plant effluents and surface waters by specific organic halogen determination. The high AOI is caused by widely used triiodinated X-ray contrast agents, which are very stable and hydrophilic. We have analysed specifically surface water influenced by a municipal treatment plant effluent, the surface water after bank filtration and raw drinking water. The X-ray contrast agents were determined by liquid chromatography-mass spectrometry with positive electrospray ionization after enrichment by solid phase extraction. Diatrizoate and iopromide, two triiodinated contrast agents are detectable in all samples, whereby the less polar component iopromide seems to be reduced during bank filtration. Just a trace of iopromide is identified in surface water after bank filtration and in the raw drinking water. Approximately 60% of the initial AOI is extractable and approximately 25% of the extractable AOI can be identified as specific triiodinated contrast agents.