Metabolites are overlooked in environmental risk assessments and monitoring of pharmaceuticals: The case study of pantoprazole.

The proton-pump inhibitor pantoprazole (PPZ) is one of the most consumed pharmaceuticals worldwide. Despite its high usage, reported PPZ concentrations in environmental water samples are comparatively low, which can be explained by the extensive metabolism of PPZ in the human body. Since most previous studies did not consider human PPZ metabolites it can be assumed that the current environmental exposure associated with the application of PPZ is substantially underestimated. In our study, 4'-O-demethyl-PPZ sulfide (M1) was identified as the predominant PPZ metabolite by analyzing urine of a PPZ consumer as well as the influent and effluent of a wastewater treatment plant (WWTP) using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). M1 was found to be ubiquitously present in WWTP effluents (max. concentration: 3 000 ng/L) and surface waters in Germany. On average, the surface water concentrations of M1 were approximately 30 times higher than those of the parent compound PPZ. Laboratory scale experiments demonstrated that activated carbon can considerably adsorb M1 und thus improve its removal during wastewater and drinking water treatment. Laboratory ozonation experiments showed a fast oxidation of M1, accompanied by the formation of several ozonation products. Certain ozonation products (identities confirmed via synthesized reference standards) were also detected in water samples collected after ozonation in a full-scale WWTP. Overall lower signal intensities were observed in the effluents of a sand filter and biologically active granular activated carbon filter, suggesting that the compounds were significantly removed during these post-ozonation treatment stages.

Trifluoroacetate in Precipitation: Deriving a Benchmark Data Set.

Although precipitation is considered to be the most important diffuse source of trifluoroacetate (TFA) to the nonmarine environment, information regarding the wet deposition of TFA as well as general data on the spatial and temporal variations in TFA concentration in precipitation is scarce. This is the first study to provide a comprehensive overview of the occurrence of TFA in precipitation by a systematic and nation-wide field monitoring campaign. In total, 1187 precipitation samples, which were collected over the course of 12 consecutive months at eight locations across Germany, were analyzed. The median, the estimated average, and the precipitation-weighted average TFA concentration of all analyzed wet deposition samples were 0.210, 0.703, and 0.335 µg/L, respectively. For Germany, an annual wet deposition flux of 190 µg/m2 or approximately 68 t was calculated for the sampling period from February 2018 to January 2019. The campaign revealed a pronounced seasonality of the TFA concentration and wet deposition flux of collected samples. Correlation analysis suggested an enhanced transformation of TFA precursors in the troposphere in the summertime due to higher concentrations of photochemically generated oxidants such as hydroxyl radicals, ultimately leading to an enhanced atmospheric deposition of TFA during summer.

Under the radar - Exceptionally high environmental concentrations of the high production volume chemical sulfamic acid in the urban water cycle.

Elevated concentrations of sulfamate, the anion of sulfamic acid, were found in surface waters and finished drinking water in Germany with concentrations up to 580 µg/L and 140 µg/L, respectively. Wastewater treatment plant (WWTP) effluent was identified as the dominant source of sulfamate in the urban water cycle, as sulfamate concentrations correlated positively (0.77 > r < 0.99) with concentrations of the wastewater tracer carbamazepine in samples from different waterbodies. Ozonation and activated sludge experiments proved that sulfamate can be formed from chemical and biological degradation of various precursors. Molar sulfamate yields were highly compound-specific and ranged from 2% to 56%. However, the transformation of precursors to sulfamate in WWTPs and wastewater-impacted waterbodies was found to be quantitatively irrelevant, since concentrations of sulfamate in these compartments are already high, presumably due to its primary use as an acidic cleaning agent. Sulfamate concentrations in the influent and effluent of studied WWTPs ranged from 520 µg/L to 1900 µg/L and from 490 µg/L to 1600 µg/L, respectively. Laboratory batch experiments were performed to assess the recalcitrance of sulfamate for chemical oxidation. In combination with the results from sampling conducted at full-scale waterworks, it was shown that common drinking water treatment techniques, including ozonation and filtration with activated carbon, are not capable to remove sulfamate. The results of biodegradation tests and from the analysis of samples taken at four bank filtration sites indicate that sulfamate is attenuated in the sediment/water interface of aquatic systems and during aquifer passage under aerobic and anaerobic conditions. Sulfamate concentrations decreased by between 62% and 99% during aquifer passage at the bank filtration sites. Considering the few data on short term ecotoxicity, about 30% of the presented sulfamate levels in ground and surface water samples did exceed the predicted no-effect concentration (PNEC) of sulfamate, and thus effects of sulfamate on the aquatic ecosystem of wastewater-impacted waterbodies in Germany cannot be excluded so far. Toxicological estimations suggest that no risk to human health is expected by concentrations of sulfamate typically encountered in tap water.

Occurrence and potential environmental risk of surfactants and their transformation products discharged by wastewater treatment plants.

Seven-day composite effluent samples from a German monitoring campaign including 33 conventional wastewater treatment plants (WWTP) were analyzed for linear alkylbenzene sulfonates (LAS) and alkyl ethoxysulfates (AES) and were screened by wide-scope suspect screening for 1564 surfactants and their transformation products (TPs) by UHPLC-ESI-QTOF-MS. Corresponding seven-day composite influent samples of selected WWTPs showed high influent concentrations as well as very high removal rates for LAS and AES. However, average total LAS and AES effluent concentrations were still 14.4 µg/L and 0.57 µg/L, respectively. The LAS-byproducts di-alkyl tetralin sulfonates (DATSs), the TPs sulfophenyl alkyl carboxylic acids (SPACs) and sulfo-tetralin alkyl carboxylic acids (STACs) reached maximum effluent concentrations of 19 µg/L, 17 µg/L and 5.3 µg/L, respectively. In many cases the sum of the concentration of all LAS-related byproducts and TPs surpassed the concentration of the precursors. High concentrations of up to 7.4 µg/L were found for 41 polyethylenoglycol homologs. Quantified surfactants and their TPs and by-products together accounted for concentrations up to 82 µg/L in WWTP effluents. To determine the risk of individual surfactants and their mixtures, single homologs were grouped by a "weighted carbon number approach" to derive normalized Predicted No-Effect Concentrations (PNEC), based on experimental ecotoxicity data from existing risk assessments, complemented by suitable Quantitative Structure-Activity Relationships (QSAR) predictions. Predicted Environmental Concentrations (PEC) were derived by dividing effluent concentrations of surfactants by local dilution factors. Risks for all analyzed surfactants were below the commonly accepted PEC/PNEC ratio of 1 for single compounds, while contributions to mixture toxicity effects from background levels of LAS and DATS cannot be excluded. Maximum LAS concentrations exceeded half of its PNEC, which may trigger country-wide screening to investigate potential environmental risks.

Transformation Products of Fluoxetine Formed by Photodegradation in Water and Biodegradation in Zebrafish Embryos ( Danio rerio).

The present study investigates the transformation of the antidepressant fluoxetine (FLX) by photo- and biodegradation and shows similarities and differences in transformation products (TPs). TPs were identified using LC-high-resolution mass spectrometry with positive and negative electrospray ionization. In a sunlight simulator, photodegradation was carried out using ultrapure water (pH 6, 8, and 10) and surface water (pH 8) to study the effect of direct and indirect photolysis, respectively. The well-known metabolite norfluoxetine (NFLX) proved to be a minor TP in photolysis (≤2% of degraded FLX). In addition, 26 TPs were detected, which were formed by cleavage of the phenolether bond ( O-dealkylation) which primarily formed 3-(methylamino)-1-phenyl-1-propanol (TP 166) and 4-(trifluoromethyl)phenol, by hydroxylation of the benzyl moiety, by CF3 substitution to benzoic aldehyde/acid, and by adduct formation at the amine group ( N-acylation with aldehydes and carboxylic acids). Higher pH favors the neutral species of FLX and the neutral/anionic species of primary TPs and, therefore, photodegradation. In zebrafish embryos, the bioconcentration factor of FLX was found to be 110, and about 1% of FLX taken up by the embryos was transformed to NFLX. Seven metabolites known from photodegradation and formed by hydrolysis, hydroxylation, and N-acylation as well as three new metabolites formed by N-hydroxylation, N-methylation, and attachment of an amine group were identified in zebrafish embryos. The study highlights the importance of considering a broad range of TPs of FLX in fresh water systems and in ecotoxicity tests and to include TP formation in both environmental processes and metabolism in organisms.

Small, mobile, persistent: Trifluoroacetate in the water cycle - Overlooked sources, pathways, and consequences for drinking water supply.

Elevated concentrations of trifluoroacetate (TFA) of more than 100 µg/L in a major German river led to the occurrence of more than 20 µg/L TFA in bank filtration based tap waters. Several spatially resolved monitoring programs were conducted and discharges from an industrial company were identified as the point source of TFA contamination. Treatment options for TFA removal were investigated at full-scale waterworks and in laboratory batch tests. Commonly applied techniques like ozonation or granulated activated carbon filtration are inappropriate for TFA removal, whereas TFA was partly removed by ion exchange and completely retained by reverse osmosis. Further investigations identified wastewater treatment plants (WWTPs) as additional TFA dischargers into the aquatic environment. TFA was neither removed by biological wastewater treatment, nor by a retention soil filter used for the treatment of combined sewer overflows. WWTP influents can even bear a TFA formation potential, when appropriate CF3-containing precursors are present. Biological degradation and ozonation batch experiments with chemicals of different classes (flurtamone, fluopyram, tembotrione, flufenacet, fluoxetine, sitagliptine and 4:2 fluorotelomer sulfonate) proved that there are yet overlooked sources and pathways of TFA, which need to be addressed in the future.