Occurrence of acidic pharmaceuticals in raw and treated sewages and in receiving waters

The occurrence of five acidic pharmaceuticals, ibuprofen, naproxen, ketoprofen, diclofenac and bezafibrate, in seven different sewage treatment plants (STP) and three receiving waters were determined. The analytical procedure included solid phase extraction, liquid chromatographic separation and detection by a triple-quadrupole mass spectrometer. The studied pharmaceuticals were found in all the STPs. The pattern of the occurrence of individual compounds was the same in every STP and matched the consumption figures reported in the literature. Ibuprofen is the most used pharmaceutical in Finland and was accordingly found to be the most abundant compound in the raw sewage. In the treatment processes, the highest removal rate was observed for ibuprofen and the lowest for diclofenac, 92%+/-8% and 26%+/-17%, respectively. Due to the incomplete removal in the STPs, the pharmaceuticals were found in rivers at the discharge points of the STP effluents. Downstream from the discharge points, the concentrations decreased significantly mainly due to dilution in the river water. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration (MEC) and predicted no-effect concentration (PNEC). At the concentrations the compounds were found in the surface waters, they should not pose risk for the aquatic environment. However, at dry seasons and/or during malfunctions of STPs, ibuprofen could be associated with a risk in small river systems.     

The occurrence of selected pharmaceuticals in wastewater effluent and surface waters of the lower Tyne catchment

This paper presents the results of a survey of the wastewater effluent and surface waters of the lower river Tyne, UK. Samples were analysed by reversed-phase high-performance liquid chromatography-electrospray tandem mass spectrometry following solid phase extraction, for the presence of 13 pharmaceuticals selected from the priority lists of the UK Environment Agency and the Oslo and Paris Commission (OSPAR). The pharmaceutical compounds measured were acetyl-sulfamethoxazole, clofibric acid, clotrimazole, dextropropoxyphene, diclofenac, erythromycin, ibuprofen, mefenamic acid, paracetamol, propranolol, sulfamethoxazole, tamoxifen and trimethoprim. Of the wastewater treatment works (WTW) samples (n=9) analysed, all compounds except sulfamethoxazole and acetyl-sulfamethoxazole were detected at concentrations ranging from 11 to 69,570 ng l(-1) (in raw effluent). In the surface water samples (n=18), clotrimazole, dextropropoxyphene, erythromycin, ibuprofen, propranolol, tamoxifen and trimethoprim were detected at concentrations ranging from 4 to 2370 ng l(-1). Results of this study show that various pharmaceutical compounds are effectively reduced during their passage through a tertiary wastewater treatment works, whilst others are sufficiently persistent to occur in estuarine systems.     

A comparison of human pharmaceutical concentrations in raw municipal wastewater and yellowwater

Currently, many articles report on pharmaceutical residues detected in various compartments of the environment. A major pathway into the aquatic environment is municipal wastewater. This article discusses the relevance of yellowwater (urine) as pharmaceutical source within this wastewater stream. Literature data about concentrations of 28 pharmaceutical residues detected in raw wastewater are compared to their theoretically calculated concentrations in urine. The study shows that these pharmaceuticals and their metabolites are excreted predominantly via urine although some substances show reasonable excretion via faeces. It is demonstrated that the influence of pharmacokinetic activities is one important issue affecting the presence of pharmaceuticals in the aquatic environment. Nevertheless, only a weak correlation between concentrations of pharmaceuticals calculated in yellowwater and analysed in raw wastewater was observed. This is due to environmental effects taking place between the excretion of urine and the entrance of sewerage into the wastewater treatment plant. The data show that urine separation and separate handling/treatment of this wastewater stream represents a promising approach to protect the aquatic environment safely from human pharmaceuticals.     

A field study on 8 pharmaceuticals and 1 pesticide in Belgium: Removal rates in waste water treatment plants and occurrence in surface water

Only recently, attention has been drawn towards the occurrence of pharmaceuticals in the environment. In recent years many reports have been made on the occurrence of the large, differentiated group of pharmaceuticals in waste water, surface water, ground water and in soil. In this study, we demonstrate the applicability of a previously developed LC-MS/MS method by evaluating in waste water and surface water samples from Belgium the occurrence of 8 pharmaceuticals and 1 pesticide (flubendazole, pipamperone, rabeprazole, domperidone, ketoconazole, itraconazole, cinnarizine, miconazole and propiconazole). Removal rates in five public waste water treatment plants were assessed. Introduction of several compounds into the aquatic environment by discharge of effluent could be demonstrated. For several compounds, the highest concentrations (up to 35.6 μg/l for pipamperone) were observed in the effluent of a WWTP receiving water from chemo-pharmaceutical and other industrial companies. The occurrence of these compounds in the aquatic environment was assessed by analyzing 16 surface water samples, taken from various locations. Four pharmaceuticals (flubendazole, pipamperone, domperidone and cinnarizine) could be detected in at least one sample at low concentrations (up to 26.4 ng/l). The pesticide propiconazole was found in comparable concentrations (up to 85.9 ng/l) as in effluent, suggesting potential introduction by direct seepage of water from rural grounds. The highest concentrations of flubendazole, pipamperone, domperidone, propiconazole and cinnarizine (up to 961.3 ng/l) were observed in a sample, taken near the discharge of a WWTP receiving water from chemo-pharmaceutical and other industries. An initial environmental risk assessment was done based on these results.     

Environmental toxicology and risk assessment of pharmaceuticals from hospital wastewater

In this paper, we evaluated the ecotoxicological potential of the 100 pharmaceuticals expected to occur in highest quantities in the wastewater of a general hospital and a psychiatric center in Switzerland. We related the toxicity data to predicted concentrations in different wastewater streams to assess the overall risk potential for different scenarios, including conventional biological pretreatment in the hospital and urine source separation. The concentrations in wastewater were estimated with pharmaceutical usage information provided by the hospitals and literature data on human excretion into feces and urine. Environmental concentrations in the effluents of the exposure scenarios were predicted by estimating dilution in sewers and with literature data on elimination during wastewater treatment. Effect assessment was performed using quantitative structure-activity relationships because experimental ecotoxicity data were only available for less than 20% of the 100 pharmaceuticals with expected highest loads. As many pharmaceuticals are acids or bases, a correction for the speciation was implemented in the toxicity prediction model.The lists of Top-100 pharmaceuticals were distinctly different between the two hospital types with only 37 pharmaceuticals overlapping in both datasets. 31 Pharmaceuticals in the general hospital and 42 pharmaceuticals in the psychiatric center had a risk quotient above 0.01 and thus contributed to the mixture risk quotient. However, together they constituted only 14% (hospital) and 30% (psychiatry) of the load of pharmaceuticals. Hence, medical consumption data alone are insufficient predictors of environmental risk. The risk quotients were dominated by amiodarone, ritonavir, clotrimazole, and diclofenac. Only diclofenac is well researched in ecotoxicology, while amiodarone, ritonavir, and clotrimazole have no or very limited experimental fate or toxicity data available. The presented computational analysis thus helps setting priorities for further testing.Separate treatment of hospital wastewater would reduce the pharmaceutical load of wastewater treatment plants, and the risk from the newly identified priority pharmaceuticals. However, because high-risk pharmaceuticals are excreted mainly with feces, urine source separation is not a viable option for reducing the risk potential from hospital wastewater, while a sorption step could be beneficial.     

Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom

The occurrence of 12 selected pharmaceutical compounds and pharmaceutical compound metabolites in sewage treatment works (STW) effluents and surface waters was investigated. The substances selected for the monitoring programme were identified by a risk ranking procedure to identify those substances with the greatest potential to pose a risk to the aquatic environment. STW final effluent and surface water samples were collected from Corby, Great Billing, East Hyde, Harpenden and Ryemeads STWs. Ten of the 12 pharmaceutical compounds were detected in the STW effluent samples: propranolol (100%, median = 76 ng/l), diclofenac (86%, median = 424 ng/l), ibuprofen (84%, median = 3086 ng/l), mefenamic acid (81%, median = 133 ng/l), dextropropoxyphene (74%, median = 195 ng/l), trimethoprim (65%, 70 ng/l), erythromycin (44%, < 10 ng/l), acetyl-sulfamethoxazole (33%, median =< 50 ng/l), sulfamethoxazole (9%, median =< 50 ng/l), tamoxifen (4%, median =< 10 ng/l). In the corresponding receiving streams, fewer compounds and lower concentrations were found: propranolol (87%, median = 29 ng/l), ibuprofen (69%, median = 826 ng/l), mefenamic acid (60%, median = 62 ng/l), dextropropoxyphene (53%, median = 58 ng/l), diclofenac (47%, median =< 20 ng/l), erythromycin (38%, median =< 10 ng/l), trimethoprim (38%, median =< 10 ng/l), acetyl sulfamethoxazole (38%, median =< 50 ng/l). Four human pharmaceutical compounds were detected in samples upstream of the STWs sampled: ibuprofen (57%, median = 181 ng/l), trimethoprim (36%, median < 10 ng/l), erythromycin (17%, median =< 10 ng/l), propranolol (14%, median =< 10 ng/l), suggesting that longer range stream transport of some compounds is possible. The particular STW that was sampled and the month that it was sampled significantly influenced the measured concentrations of several, but not all, substances. There was no significant relationship between usage data and the overall frequency with which different substances were detected. There was however, some evidence to suggest that usage data are positively associated with concentrations of pharmaceuticals in effluent and, particularly, with concentrations measured in surface waters below STWs. These results suggest that most sewage treatment works in England and Wales are likely to be routinely discharging small quantities of pharmaceuticals into UK rivers. None of the pharmaceuticals were found at concentrations that were high enough to cause acute toxic impacts to aquatic organisms. However, insufficient data were available to be able to comment on whether the concentrations measured have the potential to result in more subtle long-term effects on aquatic organisms (e.g. effects on growth, ability to reproduce).     

Pharmaceutical compounds in the wastewater process stream in Northwest Ohio

In order to add to the current state of knowledge regarding occurrence and fate of Pharmaceutical and Personal Care Products (PPCP's) in the environment, influent, effluent and biosolids from three wastewater treatment facilities in Northwest Ohio, USA, and a stream containing effluent discharge from a rural treatment facility were analyzed. The three WWTP facilities vary in size and in community served, but are all Class B facilities. One facility was sampled multiple times in order to assess temporal variability. Twenty compounds including several classes of antibiotics, acidic pharmaceuticals, and prescribed medications were analyzed using ultrasonication extraction, SPE cleanup and liquid chromatography-electrospray ionization tandem mass spectrometry. The highest number of compounds and the greatest concentrations were found in the influent from the largest and most industrial WWTP facility. Short-term temporal variability was minimal at this facility. Many compounds, such as clarithromycin, salicylic acid and gemfibrizol were found at concentrations more than one order of magnitude higher than found in the effluent samples. Effluent waters contained elevated levels of carbamazepine, clindamycin and sulfamethoxazole. Differences in composition and concentration of effluent waters between facilities existed. Biosolid samples from two different facilities were very similar in PPCP composition, although concentrations varied. Ciprofloxacin was found in biosolids at concentrations (up to 46 mug/kg dry mass) lower than values reported elsewhere. Diclofenac survived the WWTP process and was found to persist in stream water incorporating effluent discharge. The low variability within one plant, as compared to the variability found among different wastewater treatment plants locally and in the literature is likely due to differences in population, PPCP usage, plant operations and/or local environment. These data are presented here for comparison with this emerging set of environmental compounds of concern.     

Occurrence and removal of antibiotics, hormones and several other pharmaceuticals in wastewater treatment plants of the largest industrial city of Korea

Occurrence and removal efficiencies of 20 pharmaceuticals and personal care products (PPCPs) including antibiotics, hormones, and several other miscellaneous pharmaceuticals (analgesics, antiepileptics, antilipidemics, antihypertensives, antiseptics, and stimulants) were investigated in five wastewater treatment plants (WWTPs) of Ulsan, the largest industrial city of Korea. The compounds were extracted from wastewater samples by solid-phase extraction (SPE) and analyzed by High-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The results showed that acetaminophen, atenolol and lincomycin were the main individual pollutants usually found in concentrations over 10 μg/L in the sewage influent. In the WWTPs, the concentrations of analgesic acetaminophen, stimulant caffeine, hormones estriol and estradiol decreased by over 99%. On the contrary, the antibiotic sulfamethazine, the antihypertensive metoprolol, and the antiepileptic carbamazepine exhibited removal efficiencies below 30%. Particularly, removal of antibiotics was observed to vary between − 11.2 and 69%. In the primary treatment (physico-chemical processes), the removal of pharmaceuticals was insignificant (up to 28%) and removal of majority of the pharmaceuticals occurred during the secondary treatment (biological processes). The compounds lincomycin, carbamazepine, atenolol, metoprolol, and triclosan showed better removal in WWTPs employing modified activated sludge process with co-existence of anoxic-oxic condition. Further investigation into the design and operational aspects of the biological processes is warranted for the efficient removal of PPCPs, particularly antibiotics, to secure healthy water resource in the receiving downstream, thereby ensuring a sustainable water cycle management.     

Occurrence of several acidic drugs in sewage treatment plants in Switzerland and risk assessment

The occurrence and fate of five acidic drugs (Mefenamic acid, Ibuprofen, Ketoprofen, Diclofenac and Clofibric acid) were analysed in three sewage treatment plants (STP) over 4-7 consecutive days. The results point out that the five substances were persistent in wastewater effluents after municipal wastewater treatment. At the most, half of Mefenamic acid was eliminated. Ibuprofen was well removed (80%) by one sewage treatment plant. The removal of Ibuprofen is dependent on the residence time of wastewater in the STPs. A long raining period induce an important decrease of removal of Ibuprofen and Ketoprofen. Removal rates showed a great variability according to sewage treatment plants and types of treatments (e.g. biological, physico-chemical). The concentrations of Ibuprofen, Mefenamic acid and Diclofenac were relatively high in the effluents (150-2000 ng/l), showing a potential contamination of surface water. An environmental risk assessment is presented. Mefenamic acid seems to present a risk for the aquatic environment, with a ratio PEC/PNEC higher than one.     

Occurrence and removal of pharmaceuticals and hormones through drinking water treatment

The occurrence of fifty-five pharmaceuticals, hormones and metabolites in raw waters used for drinking water production and their removal through a drinking water treatment were studied. Thirty-five out of fifty-five drugs were detected in the raw water at the facility intake with concentrations up to 1200 ng/L. The behavior of the compounds was studied at each step: prechlorination, coagulation, sand filtration, ozonation, granular activated carbon filtration and post-chlorination; showing that the complete treatment accounted for the complete removal of all the compounds detected in raw waters except for five of them. Phenytoin, atenolol and hydrochlorothiazide were the three pharmaceuticals most frequently found in finished waters at concentrations about 10 ng/L. Sotalol and carbamazepine epoxide were found in less than a half of the samples at lower concentrations, above 2 ng/L. However despite their persistence, the removals of these five pharmaceuticals were higher than 95%.     

Occurrence of emerging contaminants, priority substances (2008/105/CE) and heavy metals in treated wastewater and groundwater at Depurbaix facility (Barcelona, Spain)

The presence of 170 pharmaceuticals, personal care products, priority substances according to the 2008/105EU Directive and four metals (Cd, Ni, Hg, Pb) have been investigated at the Llobregat delta, south of Barcelona (Spain). In the area, reclaimed water is destined to satisfy environmental uses, irrigation and the construction of a hydraulic barrier against seawater intrusion in the deep aquifer of the delta. A monitoring survey was undertaken of water samples from a tertiary wastewater treatment plant (Depurbaix), treated waste water with an additional treatment of ultrafiltration, reverse osmosis, and UV disinfection (WWATP, for the hydraulic barrier injection). Groundwater samples from the aquifer receiving recharge were also investigated. The pharmaceutical group of substances was detected in sampled waters at concentrations rarely exceeding a few μg/L, among the compounds Caffeine, Nicotine and Galaxolide (musk fragrance) were found to be present in more than 60% of the samples. Diuron was the only priority substance detected. The four metals were always present in a variable concentration. After the WWATP treatment the majority of analytes are removed from tertiary treated wastewater or their concentration is reduced below 0.1 μg/L. Monitoring revealed a widespread occurrence of analysed compounds in groundwater. Among them Codeine (analgesic), Ibuprofen (anti-inflammatory), Iopamidol, Iopromide (contrast agent) and Paraxanthine (metabolite of caffeine) have only been detected in groundwater, and are not present in water currently being injected in the deep aquifer.     

Seasonal variations of several pharmaceutical residues in surface water and sewage treatment plants of Han River, Korea

We collected influent and effluent samples from four sewage treatment plants (STPs) as well as surface water samples in Han River of Seoul, Korea, in three sampling events representing different flow conditions, i.e., April, June, and August, 2005, and analyzed for eleven pharmaceuticals including acetaminophen, caffeine, carbamazepine, cimetidine, diltiazem, trimethoprim, and five sulfonamide antibiotics, using LC-MS-ESI. Pharmaceuticals of high annual production amount were detected in higher level in STP influents. Levels of pharmaceutical residues in the influents were the highest for acetaminophen (average 27,089 ng/L), followed by caffeine (23,664 ng/L), cimetidine (8045 ng/L), and sulfamethoxazole (523 ng/L). Levels of acetaminophen and caffeine in STP effluents were very low compared to the influent concentrations. However cimetidine was detected in relatively high levels even in STP effluent samples. In effluent samples, cimetidine showed the highest level (5380 ng/L), followed by caffeine (278 ng/L), sulfamethoxazole (193 ng/L), and carbamazepine (111 ng/L). The concentration of cimetidine was also the highest in surface water samples (average 281 ng/L), which is the highest level reported from surface water worldwide to our knowledge. Caffeine (268.7 ng/L), acetaminophen (34.8 ng/L), and sulfamethoxazole (26.9 ng/L) were also detected in relatively high levels. Levels of pharmaceuticals detected in surface water samples upstream STPs were generally very low compared to the downstream samples, suggesting that the STPs potentially be a major source of the test pharmaceuticals into Han River. The hazard quotients (HQs) were calculated for the test pharmaceuticals based on their occurrences in surface water, and no pharmaceutical resulted in HQ greater than one, suggesting that their potential environmental impact may be low.     

Standardized tests fail to assess the effects of antibiotics on environmental bacteria

Pharmaceuticals are designed and used because of their specific biological effects. Over the past decade, compounds from various classes of pharmaceuticals have been detected in the environment. Concern has grown about the adverse effects pharmaceuticals in the environment might potentially have on human and ecological health. A sound risk assessment is therefore urgently needed for pharmaceuticals. Standardized tests for assessing the effects of chemicals on environmental organisms are widely used for this purpose. However it is questionable whether classical standardized tests give reliable data needed for environmental risk assessment. In this study we investigated the suitability of the respiration inhibition test OECD 209 for the assessment of the effects of antibiotics, disinfectants and cytotoxics on sewage sludge bacteria. We found that inhibition concentrations can strongly depend on the test period and the type of compound. We conclude that tests to assess the effects of pharmaceuticals on environmental organisms such as bacteria have to be evaluated before their results can be used in environmental risk assessment.     

Effect of phosphorus stripping on water chemistry and diatom ecology in an eastern lowland river

The effect of nutrient removal at Ashford sewage treatment works on the benthic diatom ecology of the River Stour was studied. This paper describes assemblages above and below the works both before and after phosphorus stripping was installed. Taxa typical of eutrophic conditions dominated all samples, including those upstream of the works, suggesting that the river was already eutrophic before receiving the sewage effluent. Once nutrient removal was installed, phosphorus concentrations measured downstream of the works were similar to those measured upstream; however, there was little change in the diatom flora. Analysis of chemical data collected from the site suggest that the river may be nitrogen-limited for part of the year, and that, even with phosphorus stripping installed, the river still exceeds the Environment Agency's proposed interim targets for phosphorus concentrations in a eutrophic river.     

Aquatic environmental assessment of the top 25 English prescription pharmaceuticals

An environmental assessment is presented for the 25 most used pharmaceuticals in the National Health Service (NHS) in England in 2000. Predicted environmental concentrations (PECs) for the aquatic environment were calculated using conservative assumptions and all PECs exceeded 1 ng l⁻¹. The calculation of predicted no-effect concentration (PNEC) based on aquatic toxicity data from the literature was possible for eleven of the pharmaceuticals. PNECs were predicted with ECOSAR for 12 of the remaining 14 but no data was available for two of the compounds. The PEC/PNEC ratio exceeded one for Paracetamol, Amoxycillin, Oxytetracycline and Mefenamic acid. Comparisons of the predicted concentrations of the compounds in sewage sludge based on either calculated sludge-water coefficients (K_d), octanol water coefficients (K_ow), acid base constants (pKa) or environmental modelling revealed large variations. No toxicity data was available for the terrestrial environment and no assessment was made.     

The use of modelling to predict levels of estrogens in a river catchment: How does modelled data compare with chemical analysis and in vitro yeast assay results?

Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and in vitro biological analysis as well as modelling predictions. Results showed that Rodbourne STW discharged less estrone (E1) than expected, but similar 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2) to those predicted by a widely cited effluent prediction model. The Exposure Analysis Modelling System (EXAMS) model was set up using measured effluent concentrations as its starting point to predict estrogen concentrations along a 10 km length of the receiving water of the River Ray. The model adequately simulated estrogen concentrations along the river when compared to July 2007 measured data. The model predicted combined estrogen equivalents in reasonable agreement with estrogenicity as measured by passive sampler (POCIS) extracts using the yeast estrogen screen. Using gauged mean flow values for 2007 the model indicated that the most important determinand for estrogen exposure in the Ray was not season, but proximity to the Rodbourne effluent. Thus, fish in the first 3 km downstream of Rodbourne were typically exposed to two or even three times more estrogens than those living 7-10 km further downstream. The modelling indicated that, assuming the effluent estrogen concentrations measured in February 2008 were typical, throughout the year the whole length of the Ray downstream of Rodbourne would be estrogenic, i.e. exceeding the 1 ng/L E2 equivalent threshold for endocrine disruption.     

Influence of pharmaceutical residues on the structure of activated sludge bacterial communities in wastewater treatment bioreactors

Concern is growing over contamination of the environment with pharmaceuticals because of their widespread use and incomplete removal during wastewater treatment, where microorganisms drive the key processes. The influence of pharmaceuticals on bacterial community structure in activated sludge was assessed in small-scale wastewater treatment bioreactors containing different concentrations (5, 50, 200 and 500 μg L⁻¹) of several commonly used pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric acid). T-RFLP analyses of the bacterial 16S rRNA genes indicated a minor but consistent shift in the bacterial community structure in the bioreactor R50 supplied with pharmaceuticals at a concentration of 50 μg L⁻¹, compared to the control reactor R0, which was operated without addition of pharmaceuticals. In the reactors operated with higher concentrations of pharmaceuticals, a greater structural divergence was observed. Bacterial community composition was further investigated by preparation of two clone libraries of bacterial 16S rRNA genes from reactors R0 and R50. Most clones in both libraries belonged to the Betaproteobacteria, among which Thauera, Sphaerotilus, Ideonella and Acidovorax-related spp. dominated. Nitrite-oxidizing bacteria of the genus Nitrospira sp., which are key organisms for the second stage of nitrification in wastewater treatment plants, were found only in the clone library of the reactor without pharmaceuticals. In addition, diversity indices were calculated for the two clone libraries, indicating a reduced diversity of activated sludge bacterial community in the reactor supplied with 50 μg L⁻¹ of each of selected pharmaceuticals.     

In vitro analysis of inflammatory responses following environmental exposure to pharmaceuticals and inland waters

Pharmaceuticals are regularly released into the environment; in particular non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Erythromycin, naproxen, furosemide and atenolol are reported to be stable for up to 1 year in the environment, which increases the risk for accumulation. In the present study we have measured the occurrence and concentration of pharmaceuticals in river Viskan (Jössabron) downstream of a sewage treatment plant in Borås, Sweden. Pharmaceuticals and water samples were tested for potential human risk by evaluating inflammatory responses (NF-κB and AP-1) using human T24 bladder epithelial cells and Jurkat T-cells. NF-κB activity in T24 cells was significantly reduced by all NSAIDs analysed (diclofenac, ketoprofen, naproxen, ibuprophen and dextropropoxyphene), but also by trimethoprim, using environmentally relevant concentrations. NF-κB and AP-1 activation was further analysed in response to water samples collected from different locations in Sweden. Dose-dependent down-regulation of AP-1 activity in Jurkat cells was observed at all locations. At two locations (Jössabron and Almenäs) down-regulation of NF-κB was observed. In contrast, the NF-κB response was potentiated by exposure to water from both locations following activation of NF-κB by treatment with heat-killed Escherichia coli. To determine the involvement of pharmaceuticals in the responses, T24 cells were exposed to the pharmaceutical mixture, based on the determined levels at Jössabron. This resulted in reduction of the NF-κB response following exposure to the pharmaceutical mixture alone while no potentiation was observed when cells were co-exposed to heat killed E. coli and pharmaceuticals. The obtained results demonstrate that the identified pharmaceuticals affect the inflammatory responses and furthermore indicate the presence of unknown substance(s) with the ability to potentiate inflammatory responses.     

The effects of pharmaceuticals on the regeneration of the cnidarian, Hydra attenuata

The Hydra attenuata regeneration assay was used to identify the teratogenic potential of 10 pharmaceuticals identified in effluent from a large city wastewater treatment plant (WWTP). Three types of solvents were used to solubilise the pharmaceuticals (DMSO, acetone and ethanol), at concentrations determined to have no significant effect on measured endpoints. On the one hand, regeneration was significantly inhibited at (nominal) concentrations of 1, 5 and 1 mg/L for gemfibrozil, ibuprofen and naproxen respectively and at the higher concentration of 50 mg/L for bezafibrate and trimethoprim. On the other hand, carbamazepine and the antibiotics sulfapyridine, oxytetracycline and novobiocin significantly increased regeneration at 25, 5, 50 and 50 mg/L respectively. Relatively high IC50 values of 0.9, 3.84, 4.9 and 22.5 mg/L were calculated for gemfibrozil, ibuprofen, naproxen and bezafibrate, respectively. However when subjected to tier two toxicity assessment under EU regulatory guidance using environmentally relevant concentrations a MEC/PNEC value>1 was calculated for gemfibrozil, ibuprofen and naproxen indicating teratogenic potential and the necessity for further tier three assessment. A toxicity index (TI) was also calculated using three different techniques, with TI values>3 (indicating teratogenic potential) found for gemfibrozil, ibuprofen, naproxen and bezafibrate and >1 (indicating a weak teratogenic potential) found for carbamazepine. These results are discussed in the context of their environmental relevance and toxic potential.     

Influence of residual organic macromolecules produced in biological wastewater treatment processes on removal of pharmaceuticals by NF/RO membranes

Increasing attention has been given to pollution of the water environment by pharmaceutical compounds discharged from wastewater treatment plants. High-pressure driven membranes such as a nanofiltration (NF) membrane and a reverse osmosis (RO) membrane are considered to be effective for control of pharmaceuticals in wastewater treatment. In practical applications of NF/RO membranes to municipal wastewater treatment, feed water for the membranes always contains organic macromolecules at concentrations of up to 10 mg-TOC/L, which are mainly composed of soluble microbial products (SMPs) produced during biological wastewater treatment such as an activated sludge process. In this study, influence of these organic macromolecules on removal of six pharmaceuticals by NF/RO membranes (UTC-60 and LF10) was investigated. Two types of biological treatment (conventional activated sludge process followed by media filtration (i.e., tertiary treatment) and treatment with a membrane bioreactor (MBR)) were examined as pretreatments for NF/RO membranes in this study. In the filtration tests with wastewater effluents, removal of the pharmaceuticals was higher than that seen with deionized pure water spiked with the pharmaceuticals. The increase was significant in the case of the NF membrane. Both alteration of membrane surface properties due to membrane fouling and association of the pharmaceuticals with organic macromolecules contributed to the increase in removal of pharmaceuticals by the membranes. Characteristics of the organic macromolecules contained in the wastewater effluents differed depending on the type of treatment, implying that removal of pharmaceuticals by NF/RO membranes is influenced by the type of pretreatment employed.