Preliminary risk assessment database and risk ranking of pharmaceuticals in the environment

There is increasing concern about pharmaceuticals entering surface waters and the impacts these compounds may have on aquatic organisms. Many contaminants, including pharmaceuticals, are not completely removed by wastewater treatment. Discharge of effluent into surface waters results in chronic low-concentration exposure of aquatic organisms to these compounds, with unknown impacts. Exposure of virulent bacteria in wastewater to antibiotic residues may also induce resistance, which could threaten human health. The purpose of this study was to provide information on pharmaceutical threats to the environment. A preliminary risk assessment database for common pharmaceuticals was created and put into a web-accessible database named "Pharmaceuticals in the Environment, Information for Assessing Risk" (PEIAR) to help others evaluate potential risks of pharmaceutical contaminants in the environment. Information from PEIAR was used to prioritize compounds that may threaten the environment, with a focus on marine and estuarine environments. The pharmaceuticals were ranked using five different combinations of physical-chemical and toxicological data, which emphasized different risks. The results of the ranking methods differed in the compounds identified as high risk; however, drugs from the central nervous system, cardiovascular, and anti-infective classes were heavily represented within the top 100 drugs in all rankings. Anti-infectives may pose the greatest overall risk based upon our results using a combination of factors that measure environmental transport, fate, and aquatic toxicity. The dataset is also useful for highlighting information that is still needed to assuredly assess risk.     

Impacts of emerging organic contaminants on freshwater resources: review of recent occurrences, sources, fate and effects

Rapid urbanization and frequent disposal of wastewater to surface water cause widespread contamination of freshwater supplies with emerging contaminants, such as pharmaceuticals, insecticides, surfactants, endocrine disruptors, including hormones. Although these organic contaminants may be present at trace levels, their adverse effects on aquatic life, animals and even humans are a growing concern. Numerous studies have been published on the occurrence and fate of emerging organic contaminants in different parts of the world, spanning a wide range of sources and aquatic environments including freshwater catchments, effluent wastewater streams, lakes, rivers, reservoirs, estuaries and marine waters. This paper reviews recent studies on the occurrence and fate of frequently detected pharmaceuticals and hormones and identifies areas that merit further research.     

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.     

Sources of pharmaceutical pollution in the New York City Watershed

An investigation was carried out in the New York City Watershed for the presence of selected pharmaceuticals. In four seasonal sampling events between August 2003 and May 2004, surface water was collected from eight reservoir keypoints and effluent was collected from four wastewater treatment plants. We evaluated the following twelve compounds: amoxicillin, atenolol, caffeine, carbamazepine, cephalexin, estrone, 17alpha-ethinylestradiol, 17beta-estradiol, ibuprofen, sulfamethoxazole, trimethoprim, and valproic acid. In the treated effluents, carbamazepine was detected most frequently (100%; concentration range: 22-551 ng/L), followed by atenolol (94%; ND - 14,200 ng/L), trimethoprim (83%; ND - 37,000 ng/L), ibuprofen (61%; ND - 14,600 ng/L), and caffeine (49%; ND - 37,200 ng/L), while estrone was detected once (56 ng/L). In the reservoir keypoint samples, only ibuprofen (2.5%; ND - 932 ng/L) and caffeine (2.9%; ND - 177 ng/L) were detected. The other analytes were not detected in any sample. It is expected that investigation of other wastewater treatment plants in the New York City Watershed would show that their effluents are also a potential source of pharmaceuticals, but that these pharmaceuticals are unlikely to be detected in the Watershed's surface waters.     

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).     

Occurrence and removal of pharmaceuticals and endocrine disruptors in South Korean surface, drinking, and waste waters

Liquid chromatography/tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) was used to measure the concentrations of 14 pharmaceuticals, 6 hormones, 2 antibiotics, 3 personal care products (PCPs), and 1 flame retardant in surface waters and wastewater treatment plant effluents in South Korea. Tris (2-chloroethyl) phosphate (TCEP), iopromide, naproxen, carbamazepine, and caffeine were quite frequently observed (>80%) in both surface waters and effluents. The analytes of greatest concentration were iopromide, TCEP, sulfamethoxazole, and carbamazepine. However, the primary estrogen hormones, 17alpha-ethynylestradiol and 17beta-estradiol, were rarely detected, while estrone was detected in both surface water and wastewater effluent. The elimination of these chemicals during drinking water and wastewater treatment processes at full- and pilot-scale also was investigated. Conventional drinking water treatment methods were relatively inefficient for contaminant removal, while efficient removal (approximately equal to 99%) was achieved by granular activated carbon (GAC). In wastewater treatment processes, membrane bioreactors (MBR) showed limited target compound removal, but were effective at eliminating hormones and some pharmaceuticals (e.g., acetaminophen, ibuprofen, and caffeine). Membrane filtration processes using reverse osmosis (RO) and nanofiltration (NF) showed excellent removal (>95%) for all target analytes.     

A simple method for the measurement of organic iodine in wastewater and surface water

Total adsorbable organic iodine (TAOI) has been used as a surrogate parameter for X-ray contrast media in municipal wastewater. Available methods require specialized equipment for pyrolyzing these compounds to convert the covalently bound iodine into iodide, which is then measured by ion chromatography. In this study we describe a simple method for liberating iodide from these compounds with Cu(II) and hydrogen peroxide. Concentrations of TAOI were measured in wastewater effluent, surface waters that were expected to be impacted by wastewater, and unimpacted surface waters. TAOI concentrations ranged between 1.9 and 16.3 microg/L I in wastewater with a median of 6.5 microg/L I. The lowest TAOI concentrations consistently were detected in a wastewater treatment plant that apparently had few hospitals within its collection area. In comparison, TAOI concentrations in surface water that was unimpacted by sewage were between 0.3 and 3.5 microg/L I. TAOI concentrations in surface waters that were impacted by sewage were consistent with the expected conservative behavior of TAOI.     

Ozone and biofiltration as an alternative to reverse osmosis for removing PPCPs and micropollutants from treated wastewater

This pilot-scale research project investigated and compared the removal of pharmaceuticals and personal care products (PPCPs) and other micropollutants from treated wastewater by ozone/biofiltration and reverse osmosis (RO). The reduction in UV₂₅₄ absorbance as a function of ozone dose correlated well with the reduction in nonbiodegradable dissolved organic carbon and simultaneous production of biodegradable dissolved organic carbon (BDOC). BDOC analyses demonstrated that ozone does not mineralize organics in treated wastewater and that biofiltration can remove the organic oxidation products of ozonation. Biofiltration is recommended for treatment of ozone contactor effluent to minimize the presence of unknown micropollutant oxidation products in the treated water. Ozone/biofiltration and RO were compared on the basis of micropollutant removal efficiency, energy consumption, and waste production. Ozone doses of 4-8 mg/L were nearly as effective as RO for removing micropollutants. When wider environmental impacts such as energy consumption, water recovery, and waste production are considered, ozone/biofiltration may be a more desirable process than RO for removing PPCPs and other trace organics from treated wastewater.     

Indicator compounds for assessment of wastewater effluent contributions to flow and water quality

Numerous studies have reported the presence of trace (i.e., ng/L) organic chemicals in municipal wastewater effluents, but it is unclear which compounds will be useful to evaluate the contribution of effluent to overall river flow or the attenuation processes that occur in receiving streams. This paper presents a new approach that uses a suite of common trace organic chemicals as indicators to assess the degree of impact and attenuation of trace organic chemicals in receiving streams. The utility of the approach was validated by effluent monitoring at ten wastewater treatment plants and two effluent-impacted rivers with short retention times (<17 h). A total of 56 compounds were particularly well suited as potential indicators, occurring frequently in effluent samples at concentrations that were at least five times higher than their limit of quantification. Monitoring data from two effluent-impacted rivers indicated that biotransformation was not important for these two river stretches, whereas photolysis attenuation was possibly important for the shallow river. The application of this approach to receiving waters and water reclamation and reuse systems will allow for more effective allocation of resources in future monitoring programs.     

The solids retention time-a suitable design parameter to evaluate the capacity of wastewater treatment plants to remove micropollutants

Micropollutants as endocrine disrupting compounds (EDC) or pharmaceuticals are of increased interest in water pollution control. Wastewater treatment plant (WWTP) effluents are relevant point sources for residues of these compounds in the aquatic environment. The solids retention time (SRT) is one important parameter for the design of WWTPs, relating to growth rate of microorganisms and to effluent concentrations. If a specific substance is degraded in dependency on the SRT, a critical value for the sludge age can be determined. In WWTPs operating SRTs below this critical value, effluent concentrations in the range of influent concentrations or a distribution according to the adsorption equilibrium have to be expected, whereas in WWTPs operating at SRTs higher than the critical value degradation will occur. Critical SRTs were determined for different micropollutants, indicating that the design criteria based on the sludge age allows an estimation of emissions. Different treatment technologies as conventional activated sludge systems and a membrane bioreactor were considered and no significant differences in the treatment efficiency were detected when operated at comparable SRT. The results of the investigations lead to the conclusion that low effluent concentrations can be achieved in WWTPs operating SRTs higher than 10 days (referred to a temperature of 10 degrees C). This corresponds to the requirements for WWTPs situated in sensitive areas according to the urban wastewater directive of the European Community (91/271/EEC) in moderate climatic zones.     

Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment

During 8 sampling campaigns carried out over a period of two years, 72 samples, including influent and effluent wastewater, and sludge samples from three conventional wastewater treatment plants (WWTPs), were analyzed to assess the occurrence and fate of 43 pharmaceutical compounds. The selected pharmaceuticals belong to different therapeutic classes, i.e. non-steroidal anti-inflammatory drugs, lipid modifying agents (fibrates and statins), psychiatric drugs (benzodiazepine derivative drugs and antiepileptics), histamine H2-receptor antagonists, antibacterials for systemic use, beta blocking agents, beta-agonists, diuretics, angiotensin converting enzyme (ACE) inhibitors and anti-diabetics. The obtained results showed the presence of 32 target compounds in wastewater influent and 29 in effluent, in concentrations ranging from low ng/L to a few μg/L (e.g. NSAIDs). The analysis of sludge samples showed that 21 pharmaceuticals accumulated in sewage sludge from all three WWTPs in concentrations up to 100 ng/g. This indicates that even good removal rates obtained in aqueous phase (i.e. comparison of influent and effluent wastewater concentrations) do not imply degradation to the same extent. For this reason, the overall removal was estimated as a sum of all the losses of a parent compound produces by different mechanisms of chemical and physical transformation, biodegradation and sorption to solid matter. The target compounds showed very different removal rates and no logical pattern in behaviour even if they belong to the same therapeutic groups. What is clear is that the elimination of most of the substances is incomplete and improvements of the wastewater treatment and subsequent treatments of the produced sludge are required to prevent the introduction of these micro-pollutants in the environment.     

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.     

Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden

The occurrence and removal rate of seven pharmaceuticals (ibuprofen, naproxen, diclofenac, fluoxetine, ofloxacin, norfloxacin, ciprofloxacin), two metabolites (norfluoxetine, clofibric acid), one degradation product (4-isobutylacetophenone) and 3 estrogens (17α-ethinylestradiol, 17β-estradiol, estrone) were studied in the inlet and outlet of a tertiary sewage treatment plant (STP) in Sweden as well as between different treatment steps in the STP which includes a conventional activated sludge step. Pharmaceuticals in raw household and raw hospital sewage streams leading to the STP were as well investigated. Hydraulic retention times (HRT) of each treatment step was considered for sampling and for the calculation of the removal rates. These rates were above 90%, except for diclofenac, clofibric acid, estrone and ofloxacin. However, only diclofenac and naproxen showed significant effluent loads (> 145 mg/d/1000 inh). Diclofenac was not eliminated during the treatment and in fact even higher concentrations were found at the effluent than in the inlet of the STP. 17α-Ethinylestradiol was not detected in any of the samples. Results indicate that a STP such as the one in Kristianstad, Sweden, with a tertiary treatment is sufficient to remove significantly most of the investigated pharmaceuticals. The chemical treatment improved the removal of several pharmaceuticals especially the antibiotics, which showed step removal rates between 55 and 70%. The expected concentration levels of the pharmaceuticals in the surface water (dilution 1 to 10) close to the outlet of the STP are below the no-observed effect-concentration (NOEC). However, despite that this would imply no important effects in the aquatic environment one cannot rule out negative consequences nearby the STP because most of the NOEC values are derived from acute toxicity data. This may underestimate the real impact of pharmaceuticals in the aquatic ecosystem.     

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.     

Occurrence and suitability of sucralose as an indicator compound of wastewater loading to surface waters in urbanized regions

Urban watersheds are susceptible to numerous pollutant sources and the identification of source-specific indicators can provide a beneficial tool in the identification and control of input loads, often times needed for a water body to achieve designated beneficial uses. Differentiation of wastewater flows from other urban wet weather flows is needed in order to more adequately address such environmental concerns as water body nutrient impairment and potable source water contamination. Anthropogenic compounds previously suggested as potential wastewater indicators include caffeine, carbamazepine, N,N-diethyl-meta-toluamide (DEET), gemfibrozil, primidone, sulfamethoxazole, and TCEP. This paper compares the suitability of a variety of anthropogenic compounds to sucralose, an artificial sweetener, as wastewater indicators by examining occurrence data for 85 trace organic compounds in samples of wastewater effluents, source waters with known wastewater point source inputs, and sources without known wastewater point source inputs. The findings statistically demonstrate the superior performance of sucralose as a potential indicator of domestic wastewater input in the U.S. While several compounds were detected in all of the wastewater effluent samples, only sucralose was consistently detected in the source waters with known wastewater discharges, absent in the sources without wastewater influence, and consistently present in septic samples. All of the other compounds were prone to either false negatives or false positives in the environment.     

Occurrence and risk assessment of acidic pharmaceuticals in the Yellow River, Hai River and Liao River of north China

Pharmaceuticals in the aquatic environment have received great attentions from the general and scientific community due to their potential impacts on ecological and human health. We investigated the occurrence of twelve acidic pharmaceuticals and herbicides (salicylic acid, clofibric acid, ibuprofen, gemfibrozil, fenoprofen, naproxen, ketoprofen, mefenamic acid, tolfenamic acid, diclofenac, meclofenamic acid and indomethacin) in surface waters of the Yellow River, Hai River and Liao River in north China during the wet and dry seasons and assessed the potential risks to aquatic organisms posed by these acidic compounds. Seven acidic compounds were detected in the rivers, including five non-steroidal anti-inflammatory drugs (salicylic acid, ibuprofen, diclofenac, mefenamic acid and naproxen), and two blood lipid regulators (clofibric acid and gemfibrozil). The concentrations for acidic pharmaceuticals in the Yellow River and Liao River were in most cases higher in the dry season than in the wet season, but the concentrations of acidic compounds in the Hai River were generally higher in July than in November. High concentrations of these detected compounds in the Yellow River, Hai River and Liao River were found more frequently at those sites located in metropolitan areas, lower reaches or river confluences. Only diclofenac and ibuprofen were found to have medium to high risks in the three rivers based on the calculated risk quotients.     

The fate of xenobiotic organic compounds in wastewater treatment plants

The effective operation of wastewater treatment plants plays an important role in minimising the release of xenobiotic compounds into the aquatic environment. Considerable effort has been expended in developing models to quantify the overall removal and fate of these compounds in biological treatment plants. A synthesis and modification of these approaches has been made and a generalised fate model for organic compounds in an activated sludge plant is presented. The influence of the different removal mechanisms, such as sorption, volatilisation and advection for chemicals with different physico-chemical properties is investigated and the important role of biotransformation is discussed. The effect of some operating parameters has been found to have an important influence upon the concentration of xenobiotic released in the sludges and final effluent. This may have significance for a wide range of ecotoxic compounds and in particular the class of compounds increasingly recognised as having the potential to disrupt endocrine activity in some aquatic vertebrates.     

Carbamazepine as a possible anthropogenic marker in the aquatic environment: investigations on the behaviour of Carbamazepine in wastewater treatment and during groundwater infiltration

Sewage treatment plant (STP) effluents are significant sources of pharmaceutical residues in surface waters, where high concentrations of the antiepileptic drug Carbamazepine have been detected. The solids retention time (SRT) is the most important parameter for the design of STPs. It relates to the growth rate of microorganisms and to effluent concentrations. The influence of SRT on the removal of Carbamazepine was studied on lab-scale plants. The results from these tests were then validated on several full-scale plants. Due to the lack of suitable receiving waters and groundwater resources, one of these STPs has to infiltrate the treated wastewater into unsaturated soil. Here, groundwater samples at equal distances from the infiltration point were taken to estimate the behaviour of Carbamazepine during soil passage and within the groundwater. This antiepileptic drug seems to be very persistent in the environment, therefore qualifying as a suitable marker for anthropogenic influences in the aquatic environment.     

The effects of environmental antidepressants on macroinvertebrates: a mini review

Pharmaceuticals and personal care products constitute one of the most common groups of contaminants in surface waters, and little is known about their impact on aquatic wildlife. The antidepressant fluoxetine is among more prevalent categories of pharmaceuticals detected in the aquatic environment. Typical surface water concentrations are in a wide range that can lead to alterations in life of aquatic macroinvertebrates. Because the mode of fluoxetine action is thought to be by modulation of the neurotransmitter serotonin, macroinvertebrates that possess relevant transporters and receptors sensitive are potentially affected by this pharmaceutical. Available information of how this emerging contaminant may affect macroinvertebrate communities is limited. This review describes the influence of pharmaceuticals on aquatic fauna in general and reports the environmental concentrations of some widely used antidepressants. Additionally, we highlighted the effects of fluoxetine as an antidepressant of concern, because of its abundance and potential for toxicity to aquatic macroinvertebrates.