Hospital-Use Pharmaceuticals in Swiss Waters Modeled at High Spatial Resolution.

A model to predict the mass flows and concentrations of pharmaceuticals predominantly used in hospitals across a large number of sewage treatment plant (STP) effluents and river waters was developed at high spatial resolution. It comprised 427 geo-referenced hospitals and 742 STPs serving 98% of the general population in Switzerland. In the modeled base scenario, domestic, pharmaceutical use was geographically distributed according to the population size served by the respective STPs. Distinct hospital scenarios were set up to evaluate how the predicted results were modified when pharmaceutical use in hospitals was allocated differently; for example, in proportion to number of beds or number of treatments in hospitals. The hospital scenarios predicted the mass flows and concentrations up to 3.9 times greater than in the domestic scenario for iodinated X-ray contrast media (ICM) used in computed tomography (CT), and up to 6.7 times greater for gadolinium, a contrast medium used in magnetic resonance imaging (MRI). Field measurements showed that ICM and gadolinium were predicted best by the scenarios using number of beds or treatments in hospitals with the specific facilities (i.e., CT and/or MRI). Pharmaceuticals used both in hospitals and by the general population (e.g., cyclophosphamide, sulfamethoxazole, carbamazepine, diclofenac) were predicted best by the scenario using the number of beds in all hospitals, but the deviation from the domestic scenario values was only small. Our study demonstrated that the bed number-based hospital scenarios were effective in predicting the geographical distribution of a diverse range of pharmaceuticals in STP effluents and rivers, while the domestic scenario was similarly effective on the scale of large river-catchments.

Prediction of micropollutant elimination during ozonation of a hospital wastewater effluent.

Determining optimal ozone doses for organic micropollutant elimination during wastewater ozonation is challenged by the presence of a large number of structurally diverse micropollutants for varying wastewater matrice compositions. A chemical kinetics approach based on ozone and hydroxyl radical (·OH) rate constant and measurements of ozone and ·OH exposures is proposed to predict the micropollutant elimination efficiency. To further test and validate the chemical kinetics approach, the elimination efficiency of 25 micropollutants present in a hospital wastewater effluent from a pilot-scale membrane bioreactor (MBR) were determined at pH 7.0 and 8.5 in bench-scale experiments with ozone alone and ozone combined with H2O2 as a function of DOC-normalized specific ozone doses (gO3/gDOC). Furthermore, ozone and ·OH exposures, ·OH yields, and ·OH consumption rates were determined. Consistent eliminations as a function of gO3/gDOC were observed for micropollutants with similar ozone and ·OH rate constants. They could be classified into five groups having characteristic elimination patterns. By increasing the pH from 7.0 to 8.5, the elimination levels increased for the amine-containing micropollutants due to the increased apparent second-order ozone rate constants while decreased for most micropollutants due to the diminished ozone or ·OH exposures. Increased ·OH quenching by effluent organic matter and carbonate with increasing pH was responsible for the lower ·OH exposures. Upon H2O2 addition, the elimination levels of the micropollutants slightly increased at pH 7 (<8%) while decreased considerably at pH 8.5 (up to 31%). The elimination efficiencies of the selected micropollutants could be predicted based on their ozone and ·OH rate constants (predicted or taken from literature) and the determined ozone and ·OH exposures. Reasonable agreements between the measured and predicted elimination levels were found, demonstrating that the proposed chemical kinetics method can be used for a generalized prediction of micropollutant elimination during wastewater ozonation. Out of 67 analyzed micropollutants, 56 were present in the tested hospital wastewater effluent. Two-thirds of the present micropollutants were found to be ozone-reactive and efficiently eliminated at low ozone doses (e.g., >80% for gO3/gDOC = 0.5).

Elimination of micropollutants during post-treatment of hospital wastewater with powdered activated carbon, ozone, and UV.

A pilot-scale hospital wastewater treatment plant consisting of a primary clarifier, membrane bioreactor, and five post-treatment technologies including ozone (O3), O3/H2O2, powdered activated carbon (PAC), and low pressure UV light with and without TiO2 was operated to test the elimination efficiencies for 56 micropollutants. The extent of the elimination of the selected micropollutants (pharmaceuticals, metabolites and industrial chemicals) was successfully correlated to physical-chemical properties or molecular structure. By mass loading, 95% of all measured micropollutants in the biologically treated hospital wastewater feeding the post-treatments consisted of iodinated contrast media (ICM). The elimination of ICM by the tested post-treatment technologies was 50-65% when using 1.08 g O3/gDOC, 23 mg/L PAC, or a UV dose of 2400 J/m(2) (254 nm). For the total load of analyzed pharmaceuticals and metabolites excluding ICM the elimination by ozonation, PAC, and UV at the same conditions was 90%, 86%, and 33%, respectively. Thus, the majority of analyzed substances can be efficiently eliminated by ozonation (which also provides disinfection) or PAC (which provides micropollutants removal, not only transformation). Some micropollutants recalcitrant to those two post-treatments, such as the ICM diatrizoate, can be substantially removed only by high doses of UV (96% at 7200 J/m(2)). The tested combined treatments (O3/H2O2 and UV/TiO2) did not improve the elimination compared to the single treatments (O3 and UV).

Removal of highly polar micropollutants from wastewater by powdered activated carbon.

Due to concerns about ecotoxicological effects of pharmaceuticals and other micropollutants released from wastewater treatment plants, activated carbon adsorption is one of the few processes to effectively reduce the concentrations of micropollutants in wastewater. Although aimed mainly at apolar compounds, polar compounds are also simultaneously removed to a certain extent, which has rarely been studied before. In this study, adsorption isotherm and batch kinetic data were collected with two powdered activated carbons (PACs) to assess the removal of the polar pharmaceuticals 5-fluorouracil (5-Fu) and cytarabine (CytR) from ultrapure water and wastewater treatment plant effluent. At pH 7.8, single-solute adsorption isotherm data for the weak acid 5-Fu and the weak base CytR showed that their adsorption capacities were about 1 order of magnitude lower than those of the less polar endocrine disrupting chemicals bisphenol A (BPA) and 17-α-ethinylestradiol (EE2). To remove 90 % of the adsorbate from a single-solute solution 14, 18, 70, and 87 mg L(-1) of HOK Super is required for EE2, BPA, CytR, and 5-Fu, respectively. Effects of solution pH, ionic strength, temperature, and effluent organic matter (EfOM) on 5-Fu and CytR adsorption were evaluated for one PAC. Among the studied factors, the presence of EfOM had the highest effect, due to a strong competition on 5-Fu and CytR adsorption. Adsorption isotherm and kinetic data and their modeling with a homogeneous surface diffusion model showed that removal percentage in the presence of EfOM was independent on the initial concentration of the ionizable compounds 5-Fu and CytR. These results are similar to neutral organic compounds in the presence of natural organic matter. Overall, results showed that PAC doses sufficient to remove >90 % of apolar adsorbates were able to remove no more than 50 % of the polar adsorbates 5-Fu and CytR and that the contact time is a critical parameter.

Hospital wastewater treatment by membrane bioreactor: performance and efficiency for organic micropollutant elimination.

A pilot-scale membrane bioreactor (MBR) was installed and operated for one year at a Swiss hospital. It was fed an influent directly from the hospital's sanitary collection system. To study the efficiency of micropollutant elimination in raw hospital wastewater that comprises a complex matrix with micropollutant concentrations ranging from low ng/L to low mg/L, an automated online SPE-HPLC-MS/MS analytical method was developed. Among the 68 target analytes were the following: 56 pharmaceuticals (antibiotics, antimycotics, antivirals, iodinated X-ray contrast media, antiinflamatory, cytostatics, diuretics, beta blockers, anesthetics, analgesics, antiepileptics, antidepressants, and others), 10 metabolites, and 2 corrosion inhibitors. The MBR influent contained the majority of those target analytes. The micropollutant elimination efficiency was assessed through continuous flow-proportional sampling of the MBR influent and continuous time-proportional sampling of the MBR effluent. An overall load elimination of all pharmaceuticals and metabolites in the MBR was 22%, as over 80% of the load was due to persistent iodinated contrast media. No inhibition by antibacterial agents or disinfectants from the hospital was observed in the MBR. The hospital wastewater was found to be a dynamic system in which conjugates of pharmaceuticals deconjugate and biological transformation products are formed, which in some cases are pharmaceuticals themselves.

Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites.

In spite of growing scientific concern about pharmaceuticals in the environment, there is still a lack of information especially with regard to their metabolites. The present study investigated ecotoxicity and genotoxicity of three widely used cytostatic agents 5-fluorouracil (5-FU), cytarabine (CYT) and gemcitabine (GemC) and their major human metabolites, i.e. alpha-fluoro-beta-alanine (FBAL), uracil-1-beta-D-arabinofuranoside (AraU) and 2',2'-difluorodeoxyuridine (dFdU), respectively. Effects were studied in acute immobilization and reproduction assays with crustacean Daphnia magna and growth inhibition tests with alga Desmodesmus subspicatus and bacteria Pseudomonas putida. Genotoxicity was tested with umu-test employing Salmonella choleraesius subsp. chol. Toxicity was relatively high at parent compounds with EC(50) values ranging from 44 microg L(-1) (5-fluorouracil in the P. putida test) to 200 mg L(-1) (cytarabine in D. magna acute test). In general, the most toxic compound was 5-FU. Studied metabolites showed low or no toxicity; only FBAL (metabolite of 5-FU) showed low toxicity to D. subspicatus and P. putida with EC(50) values 80 and 140 mg L(-1), respectively. All parent cytostatics showed genotoxicity with minimum genotoxic concentrations (MGC) ranging from 40 to 330 mg L(-1). From metabolites, only FBAL was genotoxic in high concentrations. To our knowledge, the present study provides some of the first ecotoxicity data for both cytostatics and their metabolites, which might further serve for serious evaluation of ecological risks. The observed EC(50) values within the microg L(-1) range were fairly close to concentrations reported in hospital sewage water, which indicates further research needs, especially studies of chronic toxicity.

Mass flows of X-ray contrast media and cytostatics in hospital wastewater.

Little is known about the significance of hospitals as point sources for emission of organic micropollutants into the aquatic environment. A mass flow analysis of pharmaceuticals and diagnostics used in hospitals was performed on the site of a representative Swiss cantonal hospital. Specifically, we analyzed the consumption of iodinated X-ray contrast media (ICM) and cytostatics in their corresponding medical applications of radiology and oncology, respectively, and their discharge into hospital wastewater and eventually into the wastewater of the municipal wastewater treatment plant. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. ICM total emissions vary substantially from day to day from 255 to 1259 g/d, with a maximum on the day when the highest radiology treatment occurred. Parent cytostatic compounds reach maximal emissions of 8-10 mg/d. A total of 1.1%, 1.4%, and 3.7% of the excreted amounts of the cytostatics 5-fluorouracil, gemcitabine, and 2',2'-difluorodeoxyuridine (main metabolite of gemcitabine), respectively, were found in the hospital wastewater, whereas 49% of the total ICM was detected, showing a high variability among the compounds. These recoveries can essentially be explained by the high amount administered to out-patients (70% for cytostatics and 50% for ICM); therefore, only part of this dose is expected to be excreted on-site. In addition, this study emphasizes critical issues to consider when sampling in hospital sewer systems. Flow proportional sampling over a longer period is crucial to compute robust hospital mass flows.

Challenge of high polarity and low concentrations in analysis of cytostatics and metabolites in wastewater by hydrophilic interaction chromatography/tandem mass spectrometry.

A method for solid phase extraction and HPLC-MS/MS of the cytostatics 5-fluorouracil, cytarabine, and gemcitabine and human metabolites uracil 1-beta-d-arabinofuranoside and 2',2'-difluorodeoxyuridine in wastewater was established. Wastewater samples from a Swiss hospital were analyzed for 5-fluorouracil, gemcitabine and 2',2'-difluorodeoxyuridine. The limits of quantification were 5.0, 0.9, and 9.0ng/L and the maximum concentrations detected were 27, 38, and 840ng/L, respectively. Along with the method development, retention mechanisms on the hydrophilic interaction chromatography (HILIC) stationary phase were studied. Both partitioning and adsorption play a role in the retention on the tested sulfoalkylbetaine modified silica HILIC column material. The contribution of these two processes is changing over the 1.6-40% range water in the mobile phase. Although the specific break point is difficult to determine, adsorption becomes more significant as the fraction of water in the mobile phase decreases below approximately 16%.