Occurrence and fate of the human pharmaceutical metabolite ritalinic acid in the aquatic system

To investigate the occurrence and fate of ritalinic acid - the main human metabolite of the psychostimulant drug methylphenidate - in the aquatic environment, a HPLC-electrospray-MS/MS method for the quantification of ritalinic acid in wastewater, surface water and bank filtrate was developed. Carbamazepine known as very stable in the aquatic environment was analyzed as anthropogenic marker in parallel. Furthermore, the removal of ritalinic acid was studied in a sewage treatment plant using an activated sludge system during a field study and in lab-scale plants. In good agreement between lab-scale and field studies a low removal rate of 13% and 23%, respectively, was determined. As a consequence, the concentration of ritalinic acid in the wastewater effluents were in the range of <50-170 ngL(-1) which corresponds to a mean specific load per capita of 17.7 μgd(-1). Ritalinic acid has further been detected in German rivers at concentrations of 4-23 ngL(-1) and in bank filtrate samples in 100-850 m distance from the river up to 5 ngL(-1) demonstrating the widespread occurrence of this stable metabolite in the aquatic environment. A comparison to available sales data shows that a significant amount of methylphenidate applied can be found in waters as ritalinic acid.     

Estimation of the cancer risk to humans resulting from the presence of cyclophosphamide and ifosfamide in surface water

Background, aim, and scope  

Anti-tumour agents and their metabolites are largely excreted into effluent, along with other pharmaceuticals. In the past, investigations have focused on the input and analysis of pharmaceuticals in surface and ground water. The two oxazaphosphorine compounds, cyclophosphamide and ifosfamide are important cytostatic drugs used in the chemotherapy of cancer and in the treatment of autoimmune diseases. Their mechanism of action, involving metabolic activation and unspecific alkylation of nucleophilic compounds, accounts for genotoxic and carcinogenic effects described in the literature and is reason for environmental concern. The anti-tumour agents cyclophosphamide (CP) and ifosfamide (IF) were not biodegraded in biodegradation tests. They were not eliminated in municipal sewage treatment plants. Degradation by photochemically formed HO radicals may be of some relevance only in shallow, clear, and nitrate-rich water bodies but could be further exploited for elimination of these compounds by advanced oxidation processes, i.e. in a treatment of hospital waste water. Therefore, CP and IF are assumed to persist in the aquatic environment and to enter drinking water via surface water. The risk to humans from input of CP and IF into surface water is not known.     

Upscaling of Environmental Information: Support of Land-Use Management Decisions by Spatio-Temporal Regionalization Approaches

This article presents several case studies in southwest Germany, which aimed to support land use management decisions by a process-oriented statistical upscaling of point-related environmental monitoring data to the landscape scale. When techniques of data subsetting were used in a sensible way and corresponding to the appropriate scale for the evaluation envisaged, multiple linear regression offered a data mining technique which was able to spatially predict relatively complex environmental patterns with parsimonious, interpretable and accurate models, whereby different evaluation scales were best represented by different DTM resolutions. Scenario models based upon the regression formulas were a valuable tool for visualizing management options and evaluating management impacts (tree species selection) on soil functions (carbon storage), which qualifies the presented methodology as a useful aid in decision making. Such upscaling techniques may be used for forecasting long-term effects of ecosystem management, but they provided no information on temporal dynamics. Therefore, time trends of point information on soil solution data were scaled by linking them to soil chemical data which was available in higher spatial resolution, using both statistical and process-oriented methods.     

Carbon dioxide fluxes over an urban park area

From September 2006 to October 2007 turbulent fluxes of carbon dioxide were measured at an urban tower station (26 m above ground level, z/z_h = 1.73) in Essen, Germany, using the eddy covariance technique. The site was located at the border between a public park area (70 ha) in the south–west of the station and suburban/urban residential as well as light commercial areas in the north and east of the tower. Depending on the land-use two different sectors (park and urban) were identified showing distinct differences in the temporal evolution of the surface-atmosphere exchange of CO₂. While urban fluxes appear to be governed by anthropogenic emissions from domestic heating and traffic (average flux 9.3 μmol m^?2 s^?1), the exchange of CO₂ was steered by biological processes when the park contributed to the flux footprint. The diurnal course during the vegetation period exhibited negative daytime fluxes up to ?10 μmol m^?2 s^?1 on average in summer. Nevertheless, with a mean of 0.8 μmol m^?2 s^?1 park sector fluxes were slightly positive, thus no net carbon uptake by the surface occurred throughout the year.In order to sum the transport of CO₂ a gap-filling procedure was performed by means of artificial neural network generalisation. Using additional meteorological inputs the daily exchange of CO₂ was reproduced using radial basis function networks (RBF). The resulting yearly sum of 6031 g m^?2 a^?1 indicates the entire study site to be a considerable source of CO₂.     

Genotoxic effect of ciprofloxacin during photolytic decomposition monitored by the in vitro micronucleus test (MNvit) in HepG2 cells

Purpose

Ciprofloxacin (CIP), a broad-spectrum, second-generation fluoroquinolone, has frequently been found in hospital wastewaters and effluents of sewage treatment plants. CIP is scarcely biodegradable, has toxic effects on microorganisms and is photosensitive. The aim of this study was to assess the genotoxic potential of CIP in human HepG2 liver cells during photolysis.

Methods

Photolysis of CIP was performed in aqueous solution by irradiation with an Hg lamp, and transformation products were monitored by HPLC-MS/MS and by the determination of dissolved organic carbon (DOC). The cytotoxicity and genotoxicity of CIP and of the irradiated samples were determined after 24?h of exposure using the WST-1 assay and the in vitro micronucleus (MN) test in HepG2 cells.

Results

The concentration of CIP decreased during photolysis, whereas the content of DOC remained unchanged. CIP and its transformation products were not cytotoxic towards HepG2 cells. A concentration-dependent increase of MN frequencies was observed for the parent compound CIP (lowest observed effect level, 1.2???mol?L^?1). Furthermore, CIP and the irradiated samples were found to be genotoxic with a significant increase relative to the parent compound after 32?min (P?P?Conclusions Photolytic decomposition of aqueous CIP leads to genotoxic transformation products. This proves that irradiated samples of CIP are able to exert heritable genotoxic effects on human liver cells in vitro. Therefore, photolysis as a technique for wastewater treatment needs to be evaluated in detail in further studies, not only for CIP but in general.     

Approach for detecting mutagenicity of biodegraded and ozonated pharmaceuticals, metabolites and transformation products from a drinking water perspective

Many pharmaceuticals and related metabolites are not efficiently removed in sewage treatment plants and enter into surface water. There, they might be subject of drinking water abstraction and treatment by ozonation. In this study, a systematic approach for producing and effect-based testing of transformation products (TPs) during the drinking water ozonation process is proposed. For this, two pharmaceutical parent substances, three metabolites and one environmental degradation product were investigated with respect to their biodegradability and fate during drinking water ozonation. The Ames test (TA98, TA100) was used for the identification of mutagenic activity present in the solutions after testing inherent biodegradability and/or after ozonation of the samples. Suspicious results were complemented with the umu test. Due to the low substrate concentration required for ozonation, all ozonated samples were concentrated via solid phase extraction (SPE) before performing the Ames test. With the exception of piracetam, all substances were only incompletely biodegradable, suggesting the formation of stable TPs. Metformin, piracetam and guanylurea could not be removed completely by the ozonation process. We received some evidence that technical TPs are formed by ozonation of metformin and piracetam, whereas all tested metabolites were not detectable by analytical means after ozonation. In the case of guanylurea, one ozonation TP was identified by LC/MS. None of the experiments showed an increase of mutagenic effects in the Ames test. However, the SPE concentration procedure might lead to false-positive results due to the generation of mutagenic artefacts or might lead to false-negative results by missing adequate recovery efficiency. Thus, these investigations should always be accompanied by process blank controls that are carried out along the whole ozonation and SPE procedure. The study presented here is a first attempt to investigate the significance of transformation products by a systematic approach. However, the adequacy and sensitivity of the methodology need to be further investigated. The approach of combining biodegradation and ozonation with effect-based assays is a promising tool for the early detection of potential hazards from TPs as drinking water contaminants. It can support the strategy for the evaluation of substances and metabolites in drinking water. A multitude of possible factors which influence the results have to be carefully considered, among them the selectivity and sensibility of the mutagenicity test applied, the extraction method for concentrating the relevant compounds and the biocompatibility of the solvent. Therefore, the results have to be carefully interpreted, and possible false-negative and false-positive results should be considered.     

Comparison of the solution behaviour of a pyrite-calcite mixture in batch and unsaturated sand column

A successful application of reaction transport algorithms to calculate the chemical evolution of natural systems requires accurate methods to compute the rates of mineral/fluid surface reactions. Regarding the transport of radio-nuclides in mining dumps the dissolution of minerals is of special importance. Using a kinetic rate law of the mineral dissolution verified for unsaturated conditions will allow a realistic modelling of the mineral weathering in the environment. Dissolution rates of minerals in an aqueous solution are determined by several characteristics. These are surface reaction rates, morphology of the mineral's surface and, in case it is the unsaturated zone, the degree of the water saturation. For this process, the quantity of the particle surfaces which are in contact with percolating water is most decisive. In order to study the differences of mineral dissolution under saturated and unsaturated conditions batch and column experiments were carried out with a pyrite-calcite mixture. The experimental results were verified by calculations. Comparing the dissolution in batch with those in the column experiment, which was performed with a water flow velocity of 0.64 cm/day and was analyzed in the region of a water saturation of 0.11, one can conclude that only a small portion of about 5% of the grain surface is chemically reactive in this unsaturated flow.     

Ultimate biodegradation and elimination of antibiotics in inherent tests

The biodegradation and elimination of antibiotics in municipal wastewater treatment plants is of particular concern because sewage is the main exposure route for antibiotics used in human medicine. The inherent biodegradability of 17 antibiotics was determined in a combined test design based on the Zahn-Wellens test (OECD 302 B, 1992) and the CO2-evolution test (OECD 301 B, 1992). CO2 Evolution test (Modified Sturm test). OECD Guideline for the Testing of Chemicals, Paris). Only benzylpenicillin sodium salt (Penicillin G) proved to be ultimately biodegradable, reaching ThCO2 degradation extents of 78-87%. Among the others, only amoxicillin, imipenem and nystatin showed certain ultimate biodegradation in few of the parallel flasks and can be regarded as partially biodegradable with formation of stable metabolites. The DOC-elimination of tetracycline-HCl showed a typical degradation curve starting with 18% and reaching the plateau phase at 80% after 21 days. Nevertheless, the CO2-evolution measured in parallel did not support the data, indicating that the time needed for reaching the adsorption equilibrium was underestimated. Several other antibiotics showed considerable DOC-elimination in the inherent test while only minor incidences of ultimate biodegradation were observed. The combination of CO2-evolution and DOC-elimination is a suitable instrument for assessing the behaviour of chemicals within one test. It enables one to assess both inherent ultimate biodegradability and DOC-elimination by sorption. The applicability of the test is limited to substances with a moderate toxicity.     

Elimination des Zytostatikums Ifosfamid während der simulierten Zersetzung von Hausmüll im Labormaßstab

Drugs are emitted into the environment by hospitals, private households, veterinary and human practices. Remnants of these products are primarily disposed of in landfill sites. At the present, there is no information available about the behaviour of pharmaceutical drugs, like their anaerobic biodegradation or adsorption, in sanitary landfills. Some of these drugs, e.g. antineoplastic substances such as ifosfamide, are supposed to be cancerogenic, mutagenic, fetotoxic or embryotoxic. Therefore, we investigated the behaviour of ifosfamide during waste decomposition in a laboratory-scale lysimeter. Up to 50% of the ifosfamide was eliminated under methanogenic conditions; but the mechanism applying for the elimination remains unclear. As far as present day knowledge is concerned, the risk for the environment through the emission of emitting ifosfamide from sanitary landfills should be negligible.