Evaluation of eight psychoactive drugs used in Chinese cities by wastewater-based epidemiology.

With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.

Multiclass target analysis of contaminants of emerging concern including transformation products, soil bioavailability assessment and retrospective screening as tools to evaluate risks associated with reclaimed water reuse.

The occurrence of 200 multiclass contaminants of emerging concern (CECs) encompassing 168 medicinal products and transformation products (TPs), 5 artificial sweeteners, 12 industrial chemicals, and 15 other compounds was investigated in influent and effluent wastewater samples collected during 7 consecutive days from 5 wastewater treatment plants (WWTPs) located in Cyprus. The methodology included a generic solid-phase extraction protocol using mixed-bed cartridges followed by Ultra-High Performance Liquid Chromatography coupled with Quadrupole-Time of Flight Mass Spectrometry (UHPLC-QTOF-MS) analysis. A total of 63 CECs were detected at least in one sample, with 52 and 55 out of the 200 compounds detected in influents and effluents, respectively. Ten (10) out of the 24 families of parent compounds and associated TPs were found in the wastewater samples (influent or effluent). 1-H-benzotriazole, carbamazepine, citalopram, lamotrigine, sucralose, tramadol, and venlafaxine (>80 % frequency of appearance in effluents) were assessed with respect to their bioavailability in soil as part of different scenarios of irrigation with reclaimed water following a qualitative approach. A high score of 12 (high probability) was predicted for 2 scenarios, a low score of 3 (rare occasions) for 2 scenarios, while the rest 28 scenarios had scores 5-8 (unlikely or limited possibility) and 9-11 (possibly). Retrospective screening was performed with the use of a target database of 2466 compounds and led to the detection of 158 additional compounds (medicinal products (65), medicinal products TPs (15), illicit drugs (7), illicit drugs TPs (3), industrial chemicals (11), plant protection products (25), plant protection products TPs (10), and various other compounds (22). This work aspires to showcase how the presence of CECs in wastewater could be investigated and assessed at WWTP level, including an expert-based methodology for assessing the soil bioavailability of CECs, with the aim to develop sustainable practices and enhance reclaimed water reuse.

Occurrence and risk assessment of pharmaceuticals in surface waters of the Middle East and North Africa: A review.

Pharmaceutical compounds in surface water are perceived as contaminants of emerging concern due to their impacts on the aquatic environment and human health. The risk associated with these compounds has not been quantified in the Middle East and North Africa (MENA). This review identified that 210 pharmaceutical compounds have been analyzed in MENA water compartments between 2008 and 2022. In fact, 151 of these substances were detected in at least one of 13 MENA countries where occurrence studies had been conducted. Antibiotics claimed the highest number of pharmaceuticals detected with concentrations ranging between 0.03 and 66,400 ng/L (for Thiamphenicol and Spiramycin respectively). To investigate whether any of these compounds exert an ecological, human health, or antibiotic resistance risk, a screening-level risk assessment was performed in surface water matrices using maximum, median, and minimum concentrations. 39 and 8 detected pharmaceuticals in MENA surface waters posed a possible risk on aquatic ecosystems and human health respectively. Extremely high risk quotients (>1000) for six pharmaceuticals (17ß estradiol, spiramycin, diclofenac, metoprolol, ethinylestradiol, and carbamazepine) were enumerated based on maximal concentrations implying an alarming risk on aquatic toxicity. Moreover, hormones posed the highest possible risk on human health whether ingested through drinking water or fish (e.g., 17ß-estradiol had a health risk quotient of 2880 for children). Spiramycin showed a high risk of antibiotic resistance with a risk quotient of 133. This review serves as a basis for future prioritization studies and regulatory guidelines in the MENA region to minimize the risks of the identified compounds.

Occurrence, ecological risk assessment and prioritization of pharmaceuticals and abuse drugs in estuarine waters along the São Paulo coast, Brazil.

The pollution of the surface waters by pharmaceuticals and personal care products (PPCPs) has attracted worldwide attention, but data regarding their occurrence and potential risks for the aquatic biota on tropical coastal rivers of South America are still scarce. In this context, the occurrence and the preliminary ecological risk assessment of eleven pharmaceuticals of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine) were investigated, for the first time, in five rivers of São Paulo, southeast Brazil, covering a coastline of about 140 km, namely Perequê River, Itinga River, Mongaguá River, Itanhaém River and Guaraú River. Although these five rivers are born in well-preserved areas of the Atlantic rainforest biome, on its way to sea and when they cross the urban perimeter, they receive untreated sewage discharges containing a complex mixture of contaminants. In addition, a "persistence, bioaccumulation and toxicity" (PBT) approach allowed to pre-select the priority PPCPs to be monitored in this coastline. Identification of several PPCPs in the samples was done using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Ten PPCPs were successfully quantified in all five rivers, namely caffeine (9.00-560.00 ng/L), acetaminophen (

First report on the occurrence of pharmaceuticals and cocaine in the coastal waters of Santa Catarina, Brazil, and its related ecological risk assessment.

The worldwide occurrence of pharmaceuticals and personal care products (PPCPs) in aquatic ecosystems is reason for public concern. These emerging micropollutants include a large and diverse group of organic compounds, with continuous input, high environmental persistence and potential threat to biota and human health. The aim of this study was to evaluate, for the first time, the occurrence of twenty-seven PPCPs of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine), in the coastal waters of Santa Catarina, southern Brazil. Water samples were taken in November 2020, during the low tide periods, at eight sampling points located along the coast of Santa Catarina, covering its entire geographical extension. Sampling was carried out in triplicate and at different depths of the water column. Nine compounds were detected through liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS): caffeine (12.58-119.80 ng/L), diclofenac (1.34-7.92 ng/L), atenolol (1.13-2.50 ng/L), losartan (0.43-3.20 ng/L), acetaminophen (0.21-10.04 ng/L), orphenadrine (0.07-0.09 ng/L), cocaine (0.02-0.17 ng/L), benzoylecgonine (0.01-1.1 ng/L) and carbamazepine (0.02-0.27 ng/L). The highest occurrence of these compounds was detected in the northern and central coastal region of Santa Catarina, namely in Penha and Palhoça cities. Moreover, the risk assessment showed that almost compounds (atenolol, benzoylecgonine, carbamazepine, cocaine and orphenadrine) presented no ecological risk in the recorded concentrations. However, a few compounds suggest low (caffeine and diclofenac) to moderate (acetaminophen and losartan) risk taking into consideration the acute and chronic effects for the three trophic levels (algae, crustacean and fish) tested. These compounds are usually found in areas with high population density, aggravated by tourism, because of the sanitary sewage and solid waste. Although in low concentrations, the occurrence of these chemical compounds can imply deleterious effects on the environmental health of Santa Catarina coastal zone, and therefore deserve more attention by the public authorities and environmental agencies.

The assessment of environmental risk related to the occurrence of pharmaceuticals in bottom sediments of the Odra River estuary (SW Baltic Sea).

The occurrence of 130 pharmaceutically active compounds (PhACs) in sediments collected from 70 sampling sites in the Odra River estuary (SW Baltic Sea) was investigated. The highest concentration levels of the compounds were found in the vicinity of effluent discharge from two main Szczecin wastewater treatment plants: "Pomorzany" and "Zdroje", and nearby the seaport and shipyard. The highest environmental risks (RQ > 1) were observed for pseudoephedrine (RQ = 14.0), clindamycin (RQ = 7.3), nalidixic acid (RQ = 3.8), carbamazepine (RQ = 1.8), fexofenadine (RQ = 1.4), propranolol (RQ = 1.1), and thiabendazole (RQ = 1.1). RQ for each compound varied depending on the sampling sites. High environmental risk was observed in 30 sampling sites for clindamycin, 22 sampling sites for pseudoephedrine, 19 sampling sites for nalidixic acid, 4 sampling sites for carbamazepine, and 3 sampling sites for fexofenadine. The medium environmental risk (0.1 < RQ < 1) was observed for 16 compounds: amisulpride, amitriptyline, amlodipine, atropine, bisoprolol, chlorpromazine, lincomycin, metoprolol, mirtazapine, moclobemide, ofloxacin, oxazepam, tiapride, tolperisone, verapamil, and xylometazoline. Due to the scarcity of toxicological data related to benthic organisms, only an approximate assessment of the environmental risk of PhACs is possible. Nevertheless, the compounds with medium and high risk should be considered as pollutants of high environmental concern whose occurrence in the environment should remain under close scrutiny.

Ecological Risk Assessment of Pharmaceuticals in the Transboundary Vecht River (Germany and The Netherlands).

Millions of people rely on active pharmaceutical ingredients (APIs) to prevent and cure a wide variety of illnesses in humans and animals, which has led to a steadily increasing consumption of APIs across the globe and concurrent releases of APIs into the environment. In the environment, APIs can have a detrimental impact on wildlife, particularly aquatic wildlife. Therefore, it is essential to assess their potential adverse effects to aquatic ecosystems. The European Water Framework Directive sets out that risk assessment should be performed at the catchment level, crossing borders where needed. The present study defines ecological risk profiles for surface water concentrations of 8 APIs (carbamazepine, ciprofloxacin, cyclophosphamide, diclofenac, erythromycin, 17α-ethinylestradiol, metformin, and metoprolol) in the Vecht River, a transboundary river that crosses several German and Dutch regions. Ultimately, 3 main goals were achieved: 1) the geo-referenced estimation of API concentrations in surface water using the geography-referenced regional exposure assessment tool for European rivers; 2) the derivation of new predicted-no-effect concentrations for 7 of the studied APIs, of which 3 were lower than previously derived values; and 3) the creation of detailed spatially explicit ecological risk profiles of APIs under 2 distinct water flow scenarios. Under average flow conditions, carbamazepine, diclofenac, and 17α-ethinylestradiol were systematically estimated to surpass safe ecological concentration thresholds in at least 68% of the catchment's water volume. This increases to 98% under dry summer conditions. Environ Toxicol Chem 2022;41:648-662. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Occurrence of carbamazepine, diclofenac, and their related metabolites and transformation products in a French aquatic environment and preliminary risk assessment.

With questions emerging on the presence and risks associated with metabolites and transformation products (TPs) of organic contaminants in the aquatic environment, progress has been made in terms of monitoring and regulation of pesticide metabolites. However, less interest is shown for pharmaceutical residues, although their pseudo-persistence and adverse effects on non-target organisms are proven. This study provides original knowledge about the contamination of ten sites located along three French rivers (water, sediments, biofilms, clams) by pharmaceutical metabolites and TPs, as well as a preliminary environmental risk assessment. Studied compounds included carbamazepine with five metabolites and TPs, and diclofenac with three metabolites and TPs. Results show that metabolites and TPs are present in all studied compartments, with mean concentrations up to 0.52 µg L-1 in water, 229 ng g-1 in sediments, 2153 ng g-1 in biofilms, and 1149 ng g-1 in clams. QSAR estimations (OECD toolbox) were involved to predict the studied compounds ecotoxicities. QSAR models showed that diclofenac and its metabolites and TPs could be more toxic than carbamazepine and its metabolites and TPs to three aquatic species representing green algae, invertebrates, and fish. However, real ecotoxicological effects are still to be determined. The environmental risk assessment showed that hydroxydiclofenac, 2-[(2-chlorophenyl)-amino]-benzaldehyde and dibenzazepine could present a greater risk than other studied compounds for aquatic organisms. In addition, the risk associated with a mixture of diclofenac and its related metabolites and TPs has been found to be greater than that of the compounds considered individually.

Modular, cost-effective, and portable capillary gradient liquid chromatography system for on-site analysis.

This work demonstrates the development of a compact, modular, cost-effective separation system configured to address a specific separation problem. The principles of the separation are based on gradient capillary liquid chromatography where the system consists of precision stepper motor-driven portable syringe pumps with interchangeable glass syringes (100 µL to 1000 µL). Excellent flow-rate precision of < 1% RSD was achieved with typical flow-rates ranging from 1 µL/min to 100 µL/min, which was ideal for capillary columns. A variable external loop volume and electrically actuated miniature injection valve was used for sample introduction. Detection was based upon a commercial Z-type UV absorbance flow-cell housed within a custom-built cooling enclosure (40 mm x 40 mm) which also contained a UV-LED light-source and a photodiode. System and chromatographic performance was evaluated using linear gradient elution, with day to day repeatability of <1.5% RSD (n = 6) for peak area, and < 0.4% RSD (n = 6) for retention time, for the separation of a 5 component mixture using a 50 mm X 530 µm ID C18 3 µm particle capillary column. The system can run any commercial or in-house packed columns from 50 mm to 100 mm length with IDs ranging from 200 to 700 µm. The developed portable system was operated using custom-built windows-based chromatography software, complete with data acquisition and system control.

A fugacity model assessment of ibuprofen, diclofenac, carbamazepine, and their transformation product concentrations in an aquatic environment.

An updated version of FATEMOD, a multimedia fugacity model for environmental fate of organic chemicals, was set up to assess environmental behaviour of three pharmaceuticals in northern Lake Päijänne, Finland. Concentrations of ibuprofen, diclofenac, and carbamazepine were estimated at various depths at two sites: near a wastewater treatment plant and 3.5 km downstream the plant. When compared with environmental sampling data from corresponding depths and sites, the predicted concentrations, ranging from nanograms to hundreds of nanograms per litre, were found to be in good agreement. Weather data were utilised with the model to rationalise the effects of various environmental parameters on the sampling results, and, e.g. the roles of various properties of lake dynamics and photodegradation were identified. The new model also enables simultaneous assessment of transformation products. Environmentally formed transformation product concentrations were estimated to be at highest an order of magnitude lower than those of the parent compounds, and unlikely to reach a detectable level. However, a possibility that conjugates of ibuprofen are present at higher levels than the parent compound was identified. Simulation results suggest that environmental degradation half-lives of the inspected contaminants under stratified lake conditions are in the range of some weeks to months.

Assessment of soil buffer capacity on nutrients and pharmaceuticals in nature-based solution applications.

The ability of a soil to sustain infiltration rates and to attenuate pollutants is critical for the design and operation of Managed Aquifer Recharge/Soil Aquifer Treatment and phyto-treatment schemes, also referred to as "Blue Infrastructures". We investigated the buffering capacity of a sediment sample and a peat soil sample for nutrients and selected pharmaceutical compounds and its evolution under continuous infiltration of secondary treated wastewater (TWW) in column experiments. Samples were obtained from two blue infrastructures, the Sant'Alessio Induced River Bank Filtration plant and the San Niccolò large-scale phyto-treatment plant in Italy, and were mainly different in their organic carbon contents (0.9 and 48%, respectively). In the column experiments, a constant infiltration rate of about 0.5 L/d was maintained for 6 months. After 4 months of operation, diclofenac and carbamazepine were spiked into the TWW to evaluate their fate. Water quality was monitored by periodic water sampling from the column inflow, at sampling ports along the column length, and at the outflow. Hydraulic conductivity (K) was also monitored. The hydraulic conductivity of the Sant'Alessio sediment decreased by a factor of 10 during the first 10 days of infiltration and then stabilized, while for the San Niccolò K (initially lower) remained constant for 50 days until it decreased following a change of the redox condition in the column. The different redox conditions, due to the two different soils tested, influenced also the concentration and mobility of PO43-, Fe, Mn, and NPOC, and the speciation of the redox sensitive elements (nitrogen and sulfur). NOPC and phosphate were enriched during the filtration through San Niccolò peat soil (from 2 to 4 times, respectively), while they were buffered by the Sant'Alessio sediment (from 0.2 to 0.4 times, respectively). Diclofenac removal (69% and below 20% for San Niccolò and Sant'Alessio, respectively) was related to sorption and degradation processes and it was lower than the removal of carbamazepine in both soils (76 and 35%). The buffer capacity differences between the two soils were higher for diclofenac (62%) than carbamazepine (35%). Nevertheless, since no apparent degradation of carbamazepine was detected in both soils, its persistence in the soil may have a larger impact in case of desorption, posing contamination risk to groundwater. The results highlight the importance of the soils or sediments to be used as medium in such nature-based solutions for their operations. They also offer an approach to, e.g., tailor man-made soil layers in infiltration basins. We strongly suggest that soil characteristics and test duration are carefully considered in designing these infrastructures, when nature-based processes are the choice for dealing with reuse of treated wastewater management issues.

A model assessment of the potential of river water to induce the photochemical attenuation of pharmaceuticals downstream of a wastewater treatment plant (Guadiana River, Badajoz, Spain).

We predicted the possible direct and indirect phototransformation kinetics of carbamazepine (CBZ), ibuprofen (IBU) and diclofenac (DIC) in river water, based on data of water chemistry obtained for the Guadiana River near Badajoz (Southwestern Spain) during a year-round sampling campaign. The three compounds were chosen, (i) because they occurred at the outlet of the wastewater treatment plant (WWTP) in Badajoz, as well as in river water sampled 1 km downstream of the WWTP, and (ii) because their photochemical fate in surface waters is known well enough to be modelled. The predicted phototransformation kinetics would be negligible in winter and fastest in April-August, with comparable rate constants in April through August despite differences in sunlight irradiance. Favourable water chemistry would in fact offset the lower irradiance, and vice versa. Half-life times of at least three weeks - one month are predicted for CBZ and IBU. Photodegradation may be an important attenuation pathway for biorecalcitrant CBZ, while IBU photochemistry is unlikely to be competitive with other processes including biodegradation. The predicted DIC photochemical half-life times of 7-10 days in April-August would be comparable with the biodegradation kinetics data reported in the literature. Photochemistry might not induce extensive phototransformation of xenobiotics in the Guadiana River under normal flow conditions, but it could become important in the case of low flow produced by water scarcity.

Investigation of pharmaceutically active compounds in an urban receiving water: Occurrence, fate and environmental risk assessment.

Pharmaceutically active compounds (PhACs) recently have been recognized to constitute a health risk for aquatic ecosystems. The major pathways of PhACs to enter the aquatic environment are excretion and discharge of effluents through sewage treatment plants (STPs). The occurrence, bioaccumulation and risk assessment of lipophilic PhACs, including erythromycin, ketoconazole, indomethacin, diclofenac, gemfibrozil, bezafibrate, propranolol, carbamazepine, sertraline and 17α-ethinylestradiol were investigated in a river that receives effluents from STP. The results indicate that the PhACs were extensively existed in fish, sediment, suspended particulate matter (SPM), colloidal phase (5 kDa to 1 µm) and truly dissolved phase (< 5 kDa) water, with total concentration of ten PhACs (Σ10PhACs) of ND-19.6 ng/g, 7.3-11.2 ng/g, 25.3-101.5 ng/g, 10.1-27.7 ng/L and 67.0-107.6 ng/L, respectively. The Σ10PhACs for particulate and water samples collected from STP's outfall site were higher than those collected from upstream and downstream, indicating that the STP is an important PhACs source of river. However, the Σ10PhACs in sediment showed no significant statistical differences in the sampling area, and which was 3.5-9.5 times lower than those in SPM samples. The colloidal phase contributed 2.5-28.5% of erythromycin, 5.8-45.6% of ketoconazole, 8.4-32.2% of indomethacin, 7.0-21.4% of diclofenac, 11.6-36.9% of gemfibrozil, 10.2-45.9% of bezafibrate, 5.9-16.8% of propranolol, 1.9-11.1% of carbamazepine and 1.1-23.8% of sertraline in the aquatic environment. This suggests that aquatic particulates (e.g., colloids and SPM) maybe an important carrier for PhACs in the aquatic system. In general, the Σ10PhACs in the tissues of fish were in order as follows: kidney > brain > liver > gill > muscle. Based on truly dissolved concentrations of PhACs in the water, bioaccumulation factors were between 3.7 and 2727.3 in the fish tissues, sertraline exhibited bioaccumulation potential. In all the risk assessments, erythromycin could cause most harmful adverse health effects for the most sensitive algae group based on the acute and chronic data. In addition, the risk quotient values for diclofenac toward fish were higher than 1. These results indicate that the PhACs pose a potential risk to the aquatic organisms, especially for chronic risk.

Assessment of Lemna minor (duckweed) and Corbicula fluminea (freshwater clam) as potential indicators of contaminated aquatic ecosystems: responses to presence of psychoactive drug mixtures.

The pharmaceutical products are emerging pollutants continuously released into the environment, because they cannot be effectively removed by the wastewater treatment plants. In recent years, questions have been raised concerning the environmental risks related to these pollutants. The goal of this research was to evaluate the responses in Lemna minor after 7 days and in Corbicula fluminea after differing durations (1, 3, 7, and 19 days) of exposure to the psychoactive drug mixture (valproic acid, citalopram, carbamazepine, cyamemazine, hydroxyzine, oxazepam, norfluoxetine, lorazepam, fluoxetine, and sertraline) in different concentrations (0, 0 + ethanol, drug concentration (DC) 1 = river water concentration, DC2 = effluent concentration, and DC3 = 10× effluent concentration). In this aim, growth parameters of L. minor, gluthathione S-transferase (GSTs), catalase (CAT), ethoxyresorufin-O-deethylase (EROD) and/or gene expressions (pi-gst, cat, cytochrome P450 4 (cyp4), multidrug resistant 1 (mdr1), and superoxide dismutase (sod)) were measured. GST activities increased significantly in L. minor exposed to DC3, but no changes were found in CAT activity. In C. fluminea, EROD activity was induced significantly in both gill and digestive gland tissues after 3 days' exposure to DC3, while a GST increase was observed only in digestive gland tissues, suggesting that these pharmaceuticals induced an oxidative effect. Gene expression analysis revealed transient transcriptomic responses of cyp4, sod, and mdr1 under drug concentrations 2 or 3 and no change of expression for the other genes (cat and pi-gst) or condition (environmental drug concentration) tested. Finally, the data reported in this study represent important ecotoxicological information, confirming that this enzyme family (cyp4, sod, and mdr1) may be considered as a sensible and early indicator of exposure to drugs and emphasizing the involvement of selected genes in detoxification pathways.

Multi-level approach for the integrated assessment of polar organic micropollutants in an international lake catchment: the example of Lake Constance.

Polar organic micropollutants (MPs) can have ecotoxicological effects on aquatic ecosystems and their occurrence in drinking water is a threat to public health. An extensive exposure assessment of MPs in large river and lake catchments is a necessary but challenging proposition for researchers and regulators. To get a complete picture of MP exposure in a large catchment, we employed a novel integrated strategy including MP measurement in the international catchment of Lake Constance and mass-flux modeling. A comprehensive screening of 252 MPs in the lake water by high-resolution mass spectrometry was used to identify the most commonly present MPs for the study site. It was found that the wastewater borne MPs diclofenac, carbamazepine, sulfamethoxazole, acesulfame, sucralose, benzotriazole, and methylbenzotriazole accounted for the most frequent and prominent findings. The concentration pattern of these compounds in the catchment was calculated based on regionalized inputs from wastewater treatment plants (WWTPs) and substance specific elimination rates. In 52, 8, and 3 of the 112 investigated river locations the concentration exceeded the predicted no-effect levels for diclofenac, sulfamethoxazole and carbamazepine, respectively. By coupling the catchment and lake model the effect of future trends in usage as well as possible mitigation options were evaluated for the tributaries and the lake. The upgrade of the major WWTPs in the catchment with a postozonation step would lead to a load reduction between 32% and 52% for all substances except for sucralose (10%).

Bioavailability of pharmaceuticals in waters close to wastewater treatment plants: use of fish bile for exposure assessment.

Pharmaceuticals are ubiquitous in surface waters as a consequence of discharges from municipal wastewater treatment plants. However, few studies have assessed the bioavailability of pharmaceuticals to fish in natural waters. In the present study, passive samplers and rainbow trout were experimentally deployed next to three municipal wastewater treatment plants in Finland to evaluate the degree of animal exposure. Pharmaceuticals from several therapeutic classes (in total 15) were analyzed by liquid chromatography-tandem mass spectrometry in extracts of passive samplers and in bile and blood plasma of rainbow trout held at polluted sites for 10 d. Each approach indicated the highest exposure near wastewater treatment plant A and the lowest near that of plant C. Diclofenac, naproxen, and ibuprofen were found in rainbow trout, and their concentrations in bile were 10 to 400 times higher than in plasma. The phase I metabolite hydroxydiclofenac was also detected in bile. Hence, bile proved to be an excellent sample matrix for the exposure assessment of fish. Most of the monitored pharmaceuticals were found in passive samplers, implying that they may overestimate the actual exposure of fish in receiving waters. Two biomarkers, hepatic vitellogenin and cytochrome P4501A, did not reveal clear effects on fish, although a small induction of vitellogenin mRNA was observed in trout caged near wastewater treatment plants B and C.

Distribution and temporal evolution of pharmaceutically active compounds alongside sewage sludge treatment. Risk assessment of sludge application onto soils.

In this work, the distribution and the ecotoxicological risk of sixteen pharmaceutically active compounds belonging to seven different therapeutic groups (five anti-inflammatory drugs, two antibiotics, an anti-epileptic drug, a ß-blocker, a nervous stimulant, four estrogens and two lipid regulators) have been studied in sewage sludge from wastewater treatment plants. Only three of the sixteen pharmaceutical compounds were never detected in sludge while eleven of the studied pharmaceuticals were still detected in compost. Mean concentration levels of the pharmaceutically active compounds ranged between 24.9 and 4105 µg/kg dm, 14.5-944 µg/kg dm, 3.29-636 µg/kg dm and 9.19-974 µg/kg dm in primary, secondary, digested sludge and compost, respectively. An increase in the concentration levels of most of the pharmaceuticals was observed from summer to winter (mean values in primary and secondary sludge were 304 and 85.1 µg/kg dm in summer and 435 and 175 µg/kg dm in winter, respectively) probably due to an increase of their consumption during the coldest season and a reduction of the microbial activity under colder temperatures. The highest ecotoxicological risk, in digested sludge and compost, was due to the estrogenic compound 17ß-estradiol. The ecotoxicological risk significantly decreased after the application of digested sludge or compost to the soils (risk quotient values ranged between 0.04 and 252 in digested sludge and 0.002-37.8 in compost and decreased to 8·10(-4)-1.92 in digested sludge-amended soil and 1·10(-4)-0.23 in compost-amended soil).

Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine.

Pharmaceutical residues have been detected at low (usually ng/L) concentrations in drinking water sources. The detection of drugs in water intended for human consumption (WIHC) has raised questions of safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which pharmaceutical residues should be monitored and the toxicological limits that should be required. In this essay, we define an approach for the assessment of health risks related to chemicals found in drinking water. We use the examples of carbamazepine and its main metabolite 10,11-epoxycarbamazepine to demonstrate our approach, which involves application of the following algorithm: (1) when there is human or animal toxicity data, a toxicity reference value (TRV) can be calculated; (2) when this is not applicable, an attempt should be made to derive the TRV using known information about the minimum therapeutic dose (MTD); and (3) when no applicable data is available, at all, a threshold of toxicological concern (TTC) should be estimated. In the case of carbamazepine, where relevant toxicological data exists, we derived a TRV, based on the known minimum therapeutic dose (MTD). For carbamazepine's metabolite 10,11-epoxycarbamazepine, there is no toxicological data, so we applied the TTC approach. Using this approach, and combining our estimates with what is known about these chemicals' margin of exposure (MOE), suggests that there is likely to be no appreciable risk to human health exposure to carbamazepine or its major metabolite, even given the inevitable uncertainties in exposure scenarios.

Assessment of groundwater pollution in Tokyo using PPCPs as sewage markers.

While the occurrence of pharmaceuticals and personal care products (PPCPs) in groundwater has typically been reported in bank filtration sites, irrigated fields, septic tanks, and sewage disposal practices, fewer studies have been conducted in highly urbanized areas, where infiltration of treated or untreated sewage is not supposed to be a source of groundwater recharge. Furthermore, little is known about the occurrence of various kinds of PPCPs in relation to microbial indicators in groundwater from different types of aquifers. Thus, we examined the city-wide occurrence of selected PPCPs (diethyltoluamide, crotamiton, ethenzamide, propyphenazone, carbamazepine, and caffeine) and E. coli in 50 groundwaters from unconfined aquifers (<30 m in depth) and confined aquifers (up to 500 m in depth) in Tokyo, where unintended groundwater contamination could take place due to decrepit sewer networks. PPCPs were detected in unconfined aquifers and springs (23/34 samples, 68%), and in confined aquifers (7/16 samples, 44%). Compared with published results for sewage influents, concentrations of PPCPs, excluding caffeine, were generally 1-2 orders of magnitude lower, while in some samples concentrations were quite comparable. The high occurrence rate of PPCPs, even in confined aquifers, indicated that such aquifers are not always protected from pollution by sewage near the land surface. Among the PPCPs analyzed, carbamazepine and crotamiton were most frequently detected, which would appear to be owing to their high persistence, combined with the high concentration of crotamiton in sewage. Crotamiton was detected in all four E. coli-positive groundwaters, and thus may potentially serve as a precautionary indicator of E. coli contamination. Using carbamazepine as a sewage marker, we estimated that 0.8%-1.7% of the dry-weather flow of sewage was leaking out into the unconfined aquifers.

GC-MS analysis and ecotoxicological risk assessment of triclosan, carbamazepine and parabens in Indian rivers.

Pharmaceutical and personal care products are used extensively worldwide and their residues are frequently reported in aquatic environments. In this study, antiepileptic, antimicrobial and preservative compounds were analyzed in surface water and sediment from the Kaveri, Vellar and Tamiraparani rivers, and in the Pichavaram mangrove in India by gas chromatography-mass spectrometry (GC-MS). The mean concentration of carbamazepine recorded in the Kaveri River water (28.3 ng/L) was higher than in the other rivers and the mangrove. Because carbamazepine is used only in human drugs, this may reflect the relative contributions of human excretions/sewage in these rivers. The mean triclosan level in the Tamiraparani River (944 ng/L) was an order of magnitude greater than in the other water systems, and the concentrations at two of the sites reported here (3800-5160 ng/L) are, to our best knowledge, among the highest detected in surface waters. Sediment levels were, however, comparable with other sites. We conclude that industrial releases are likely major contributors of triclosan into this river system. Among parabens, ethyl paraben was predominantly observed. Hazard Quotients suggest greater environmental risks for triclosan than for carbamazepine and parabens. This is the first study on antiepileptic, antimicrobial and preservatives in rivers and mangroves from India.