Environmental Risk Assessment Of Pharmaceuticals Research Articles

Occurrence, transport and environmental risk assessment of pharmaceuticals and personal care products (PPCPs) at the mouth of Jiaozhou Bay, China based on stir bar sorptive extraction.

In recent years, research on pharmaceuticals and personal care products (PPCPs) in the marine environment has attracted increasing attention worldwide. However, more work is needed to improve PPCPs detection methods, specifically for seawater environments. An analytical method based on stir bar sorptive extraction (SBSE) had been developed and fully optimized for the pretreatment and detection of ten widely used PPCPs that are commonly found in seawater samples. By optimizing several variables including the material of the stir bars, extraction temperature, extraction time, ionic strength, desorption solvent, and desorption time, the optimized method has achieved excellent results in the detection and quantification of target PPCPs with detection limits ranging from 0.03 to 1ng/L. The distribution of target PPCPs at the mouth of Jiaozhou Bay was successfully determined by this method, and the concentrations and detection frequencies of PPCPs varied greatly from N.D. to 449.36ng/L and from 9.1% to 100%, respectively. Moreover, the distributions of PPCPs were explained by the Lagrangian particle-tracking model, and the results showed that the Tuandao sewage treatment plant had the most significant impact on the study area. The environmental risk assessment results showed that several target PPCPs might pose risks to aquatic organisms. In particular, triclocarban should receive more attention and the risk quotients of the mixtures (MRQ) should not be ignored.

Are newer pharmaceuticals more recalcitrant to removal in wastewater treatment?

• mass, lipophilicity, biodegradability and removal of 1850 pharmaceuticals modelled •corresponding experimental data for ≥248 pharmaceuticals was collated • mass and lipophilicity globally increased over time, while biodegradability decreased • Predicted removal in wastewater treatment increased, but only through adsorption • EPISuite may be useful for environmental risk assessment of pharmaceuticals

A Generalized Physiologically Based Kinetic Model for Fish for Environmental Risk Assessment of Pharmaceuticals.

An increasing number of pharmaceuticals found in the environment potentially impose adverse effects on organisms such as fish. Physiologically based kinetic (PBK) models are essential risk assessment tools, allowing a mechanistic approach to understanding chemical effects within organisms. However, fish PBK models have been restricted to a few species, limiting the overall applicability given the countless species. Moreover, many pharmaceuticals are ionizable, and fish PBK models accounting for ionization are rare. Here, we developed a generalized PBK model, estimating required parameters as functions of fish and chemical properties. We assessed the model performance for five pharmaceuticals (covering neutral and ionic structures). With biotransformation half-lives (HLs) from EPI Suite, 73 and 41% of the time-course estimations were within a 10-fold and a 3-fold difference from measurements, respectively. The performance improved using experimental biotransformation HLs (87 and 59%, respectively). Estimations for ionizable substances were more accurate than any of the existing species-specific PBK models. The present study is the first to develop a generalized fish PBK model focusing on mechanism-based parameterization and explicitly accounting for ionization. Our generalized model facilitates its application across chemicals and species, improving efficiency for environmental risk assessment and supporting an animal-free toxicity testing paradigm.

Occurrence, sources and environmental risk assessment of pharmaceuticals in the Sea of Marmara, Turkey

In the present study, the occurrence and spatial distribution of selected eleven pharmaceuticals were investigated in the Sea of Marmara, Turkey. Samples were collected from different depths of the nine stations in April and October 2019. Pharmaceuticals were analyzed using liquid-liquid and solid-phase extraction (SPE) methods followed by high-performance liquid chromatography (HPLC). All target pharmaceutical compounds were detected at least once in the study area. Gemfibrozil, which belongs to the lipid regulatory group, was the most frequently detected in seawater at high concentrations (<0.016–9.71 μg/L). Ibuprofen (<0.015–2.13 μg/L) and 17α-ethynylestradiol (<0.010–3.55 μg/L) were identified as the other frequently detected pharmaceuticals. In addition, the presence of these selected compounds in April was higher than in October. According to the risk assessment results, naproxen, diclofenac, clofibric acid, gemfibrozil, 17β-estradiol, and 17α-ethynylestradiol represent a high risk to aquatic organisms in the Sea of Marmara. These findings underline the importance of continued monitoring of these compounds as relevant organic contaminants in the study area to take appropriate measures to protect the ecosystem and, ultimately, human health.

Environmental risk assessment of pharmaceuticals at a seasonal holiday destination in the largest freshwater shallow lake in Central Europe

The presence of pharmacologically active compounds (PhACs) in surface waters poses an environmental risk of chronic exposure to nontarget organisms, which is a well-established and serious concern worldwide. Our aim was to determine the temporal changes in ecological risk quotient (RQ) based on the concentrations of 42 PhACs from six sampling sites on seven sampling dates in the water of a freshwater lake in Central Europe preferentially visited by tourists. Our hypothesis was that the environmental risk increases during the summer holiday season due to the influence of tourists. Different experimental toxicological threshold concentrations and seasonal measured environmental concentrations of 16 PhACs were applied to ecological risk assessment. RQs of 4 dominant PhACs (diclofenac, estrone [E1], estradiol [E2], and caffeine) indicated high ecological risk (RQ > 1) for freshwater ecosystems. Additionally, our results confirmed the assumptions that the high tourist season had a significant impact on the calculated RQ; however, these results are mainly due to the concentration and temporal change of particular PhACs, including diclofenac (5.3-419.4 ng/L), E1 (0.1-5.5 ng/L), and E2 (0.1-19.6 ng/L). The seasonal dependent highest RQs changed as follows: 9.80 (June 2017; E2), 1.23 (August 2017; E1), 0.43 (November 2017; E1), 0.51 (April 2018; E1), 5.58 (June 2018, diclofenac), 39.50 (August 2018; diclofenac), and 30.60 (October 2018; diclofenac).

Temporal-spatial variation and environmental risk assessment of pharmaceuticals in tributaries of the Han River watershed, South Korea

Eight compounds from three categories of pharmaceuticals [5 antibiotics, 2 non-steroidal anti-inflammatory drugs, and 1 anti-epileptics] were monitored at 24 sites in the tributaries of the Han River watershed in South Korea, 2016. The seasonal occurrence, temporal-spatial variation, potential compound source(s), and a risk assessment of this watershed, which is the largest drinking water source in the country, were investigated. Clarithromycin was detected most frequently (72.2%) with the greatest median concentration (0.151 ± 0.072 μg L−1), followed by carbamazepine and sulfamethoxazole. The seasonality of the pharmaceuticals was observed, with higher concentrations and detection frequencies in spring than in summer and autumn; this was possibly caused by lower levels of microbial activities associated with lower water temperatures than other seasons. In terms of geographical variation, urban areas had higher pharmaceutical concentrations than rural areas, which was attributed to the former's high population density and largest wastewater treatment plants (WWTPs) regardless of season. The total concentration and detection frequency of WWTPs were 12.4 and 2.5 times higher in downstream sites than upstream sites, thereby conveying that WWTPs were the main source for the presence of pharmaceuticals in tributaries. According to the results produced from calculations of the risk quotient (RQ) of aquatic organisms, clarithromycin and sulfamethazine were identified as posing relatively high ecological risk (RQ > 1) during the spring that was identified for this study. This study can provide policymakers with scientific support for prioritizing pollutant management and collections of global data on emerging pollutants.

Hazardous impact of diclofenac exposure on the behavior and antioxidant defense system in Nauphoeta cinerea

Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to the ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate the impact of DCF on insects by assessing the behavior and antioxidant defense response in nymphs of N. cinerea exposed to DCF-contaminated food at 0, 0.5, 1.0 and 2.0 μg kg−1 feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in the head, midgut and hemolymph of the insects. Results indicated that DCF-exposed insects exhibited marked reduction in the maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas the total freezing time was increased compared with the control. The diminution in the exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in the head, midgut and hemolymph of the insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.

The influence of nanoplastics on the toxic effects, bioaccumulation, biodegradation and enantioselectivity of ibuprofen in freshwater algae Chlorella pyrenoidosa

Plastic pollution has become a pressing issue due to its persistence in the environment. Smaller plastics are more easily ingested, potentially exerting greater influences on organisms. In this study, the effects of polystyrene nanoplastics (NP) on the toxic effects, bioaccumulation, biodegradation and enantioselectivity of ibuprofen (IBU) in algae Chlorella pyrenoidosa were explored. The influences on the growth rate, chlorophyll a, total antioxidant capacity (T-AOC), reactive oxygen species (ROS) and lipid peroxidation (MDA) were evaluated after 96 h of exposure to a combination of polystryene NP (1 mg L−1) and IBU (5–100 mg L−1). The results indicated that the inhibitory effect of IBU on C. pyrenoidosa growth was alleviated in the presence of NP. For instance, the 96 h-IC50 value for rac-IBU in the treatment lacking NP was 45.7 mg L−1, and the corresponding value in the treatment containing NP was 63.9 mg L−1. The co-exposure of NP led to a significant enhancement of T-AOC and slight reduction of ROS and MDA compared with the individual exposure (IBU) group, suggesting a decreased oxidative stress. In addition, treatment with NP led to a decreased bioaccumulation and accelerated biodegradation of IBU in C. pyrenoidosa and enhanced removal in the medium. The enantioselective toxicity, bioaccumulation and biodegradation of IBU were observed both in the absence and presence of NP. S-IBU exhibited a greater toxicity, and R-IBU was preferentially accumulated and degraded in C. pyrenoidosa. No interconversion of the two enantiomers occurred regardless of the presence of NP. This consequence implied that the influence of coexistent NP should be considered in the environmental risk assessment of pharmaceuticals and personal care products in aquatic environments.

The accessibility of data on environmental risk assessment of pharmaceuticals – are environmental risk assessments information on emissions with respect to international and European environmental information law?

In the pharmaceutical sector, the right of access to environmental information is in most cases not feasible as the authorisation holders refer to commercially/industrial confidential information (CCI). However, CCI can not refuse access to environmental risk assessments (ERAs) if ERAs are to be classified as information on emissions.Pharmaceuticals inevitably enter the environment as a consequence of their intended use. This release is calculated in the ERA as predicted environmental concentration when a pharmaceutical is approved. The release of pharmaceuticals into the environment falls consequently under the term ‘emissions into the environment’. In addition, the ERAs assessing the risk of this release are to be classified as ‘information on emissions into the environment’.Therefore, the practiced secrecy of ERAs of pharmaceuticals and their official assessment reports is incompatible with Art. 4 Aarhus Convention, and the European and national implementing provisions for this article, which require access to such environmental information on emissions for everyone, irrespective of whether they concern CCI.With this legal disclosure obligation of ERAs, there is an enforceable right of access for everyone, which shows the necessity for establishing a publicly accessible database based on active pharmaceutical ingredients with substantiated information on the ERAs.

The accessibility of data on environmental risk assessment of pharmaceuticals: Is the marketing authorisation procedure in conflict with the international right of access to environmental information?

BackgroundFor a large part of the active pharmaceutical ingredients (APIs) available on the market, there is no or no comprehensive environmental risk assessment (ERA) existent/available. Existing ERAs are, moreover, treated as commercially/industrial confidential information (CCI) and the information content on the ERAs contained in the Public Assessment Reports is very limited. Thus, neither the public can inform itself sufficient nor environmental authorities can use the ERAs to compile environmental quality standards. Environmental information law, on the other hand, requires the general accessibility of environmental information. Against this background, this investigation examines the following questions in conformity with the environmental information law: Which environmental information on pharmaceuticals is generated in the marketing authorisation? Which of the environmental information generated in the marketing authorisation is available to the public? Does the environmental information on pharmaceuticals concern CCI?ResultsAccording to international and European environmental information law, there is in principal a right of access to the ERAs of pharmaceuticals (environmental information according to Art. 2(3)(b) Aarhus Convention), which is ineffective due to product-based data and allegedly conflicting CCI. The practised blanket classification of CCI by the marketing authorisation holders is in conflict with the principle of transparency of environmental information law. In any case, the outcomes of the ERA (in particular the ecotoxicity endpoints) may not be classified as CCI. Furthermore, the publicly accessible information in the format of the Public Assessment Report does not sufficiently reflect the information from ERAs and thus does not fulfil the mandate of active access to information (Art. 5 Aarhus Convention). The conflict between the actual accessibility of environmental information on pharmaceuticals and the requirements of environmental information law could be resolved through an API-based publicly accessible database with the outcomes of the ERAs (including all underlying ecotoxicity endpoints). To fulfil the right of access to environmental information effectively, the database also needs to be extended to “old” APIs for which environmental risk assessments have not yet been carried out. This would be the basis for prioritisation of API and establishing a monograph system.ConclusionThe environmental information law requires an improved accessibility of ERAs that could be achieved through an API-based publicly accessible database.

Local environmental risk assessment of anticancer drugs in a developing country

Anticancer drugs used in cancer treatment are excreted unchanged or as metabolites by feces and urine in hospitals and households. These drugs enter the municipal sewage system but wastewater treatment plants are not capable of removing all of these micro pollutants. In many countries such as Brazil, sanitation departments do not provide service, nor have access to all of the population, therefore most sewage is still released into untreated receiving bodies. This study analyzes the consumption of anticancer drugs in a Brazilian hospital located in one of the 10 municipalities with the best sanitation index in the country. It estimates its environmental risk in aquatic matrixes by the European Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. Among the 20 drugs analyzed, the three most consumed (cyclophosphamide, 5-fluoruracil, and cytarabine) show a predicted environmental concentration value greater than the action limit of 0.01 µg/L recommended by the guideline. The risk assessment was performed on all pharmaceuticals consumed to get a greater awareness of risk. Results do not indicate local environmental risk but, considering that the study was performed under the best sanitation scenario, it cannot be extrapolated in the other municipalities. The study highlights that development of suitable methodologies should be considered to perform environmental risk assessment of pharmaceuticals in developing countries sanitation conditions.

Chronic amoxicillin exposure affects Labeo rohita: assessment of hematological, ionic compounds, biochemical, and enzymological activities

Labeo rohita were exposed to amoxicillin at a concentration of 1 mg/L (Treatment -I) and 0.5 mg/L (Treatment-II) for a period of 35 days. Numerous alterations were found in amoxicillin treatment groups when compared to the control group. Hemoglobin (Hb), hematocrit (Hct), and erythrocytes (RBCs) levels were significantly (P < 0.05) decreased. Leukocytes (WBC), mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) levels were significantly (P < 0.05) increased. In the plasma and gill tissues, ionic compounds (sodium, potassium, and chloride) levels were significantly declined throughout the treatment period. The plasma biochemical profiles were significantly altered: glucose level remained low (except at the end of 7th day in Treatment -I) till 35 days of the treatment period. Biphasic trend occurred in the protein level, significant increase was observed on 7th and 28th day (Treatment -I and -II), and 35th day (Treatment -I), and in remaining days its level was found to be decreased. Glutamate oxaloacetate transaminase (GOT) activity in the plasma was inhibited significantly, whereas in the gill, liver, and kidney tissues the enzyme activity was elevated. Plasma glutamate pyruvate transaminase (GPT) activity was inhibited throughout the study period. GPT activity in the gill was found to be elevated during the treatment period. Liver GPT activity was elevated in all the treatments except 28th (Treatment-I) and 35th day (Treatment-I, and II). GPT activity in the kidney was elevated (except 14th day in Treatment-II). Lactate dehydrogenase (LDH) activity was inhibited in plasma (except 14th day in Treatment-II), gill, liver (except 7th day in Treatment-I), and kidney tissues significantly (P < 0.05). The present study emphasizes that amoxicillin at 1 and 0.5 mg/L concentrations affects the hematological/biochemical/electrolytes/enzymological parameters of fish and these biomarkers serve as an effective test system for environmental risk assessment of pharmaceuticals in the aquatic environment.

Spatially Explicit Large-Scale Environmental Risk Assessment of Pharmaceuticals in Surface Water in China.

With improving healthcare and an aging population, the consumption of human pharmaceuticals in China has been increasing dramatically. Environmental risks posed by many active pharmaceutical ingredients (APIs) are still unknown. This study used a spatially explicit dilution-factor methodology to model predicted environmental concentrations (PECs) of 11 human-use APIs in surface water for a preliminary environmental risk assessment (ERA). Median PECs in surface water across China range between 0.01 and 8.0 × 103 ng/L for the different APIs, under a moderate patient use scenario. Higher environmental risks of APIs in surface water are in regions with high water stress, e.g., northern China. Levonorgestrel, estradiol, ethinyl estradiol and abiraterone acetate were predicted to potentially pose a high or moderate environmental risk in China if consumption levels reach those in Europe. Relative risks of these four APIs have the potential to be among those chemicals with the highest impact on surface water in China when compared to the risks associated with other regulated chemicals, including triclosan and some standard water quality parameters including BOD5 (5-day biological oxygen demand), COD (chemical oxygen demand), Cu, Zn, and Hg and linear alkylbenzene sulfonate. This method could support the regulation of this category of chemicals and risk mitigation strategies in China.

A High-Resolution Spatial Model to Predict Exposure to Pharmaceuticals in European Surface Waters: ePiE.

Environmental risk assessment of pharmaceuticals requires the determination of their environmental exposure concentrations. Existing exposure modeling approaches are often computationally demanding, require extensive data collection and processing efforts, have a limited spatial resolution, and have undergone limited evaluation against monitoring data. Here, we present ePiE (exposure to Pharmaceuticals in the Environment), a spatially explicit model calculating concentrations of active pharmaceutical ingredients (APIs) in surface waters across Europe at ∼1 km resolution. ePiE strikes a balance between generating data on exposure at high spatial resolution while having limited computational and data requirements. Comparison of model predictions with measured concentrations of a diverse set of 35 APIs in the river Ouse (UK) and Rhine basins (North West Europe), showed around 95% were within an order of magnitude. Improved predictions were obtained for the river Ouse basin (95% within a factor of 6; 55% within a factor of 2), where reliable consumption data were available and the monitoring study design was coherent with the model outputs. Application of ePiE in a prioritisation exercise for the Ouse basin identified metformin, gabapentin, and acetaminophen as priority when based on predicted exposure concentrations. After incorporation of toxic potency, this changed to desvenlafaxine, loratadine, and hydrocodone.

Influence of photolabile pharmaceuticals on the photodegradation and toxicity of fluoxetine and fluvoxamine.

Pharmaceuticals in the aquatic environment may be decomposed by abiotic and biotic factors. Photodegradation is the most investigated abiotic process, as it occurs in the natural environment and may be applied in wastewater treatment technology. Although pharmaceuticals are detected in effluents and surface water in a mixture, the photodegradation process is mainly evaluated with single compounds. The photodegradation of fluoxetine (FLU) and fluvoxamine (FLX) in the presence of diclofenac (DCF) and triclosan (TCS) was investigated with HPLC and bioassay. FLU did not degrade under UV-Vis irradiation in SunTest CPS+ either with or without the tested additives, although small amounts of desmethyl fluoxetine and 4-(trifluoromethyl)phenol were formed. In contrast, during irradiation, FLX isomerized to cis-FLX. This process was enhanced by DCF and TCS, but to a lesser degree than by humic acids. Thus, the presence and composition of the matrix should be considered in the environmental risk assessment of pharmaceuticals. As the toxicity of the tested solutions depended only on the concentration of the tested drugs, it was suggested that the biological activity of the photodegradation products was lower than that of the parent compounds.

Sex steroids and metabolic responses in mussels Mytilus galloprovincialis exposed to drospirenone

Drospirenone (DRO) is a synthetic progestin derived from 17α-spironolactone with a pharmacological mechanism of action similar to progesterone. Despite its wide use as pharmaceutical and consequent continuous release into the aquatic environment, DRO effects have been poorly investigated on aquatic biota. In order to unravel the toxicity mechanisms of DRO, mussels Mytilus galloprovincialis were exposed for 7 days to different concentrations of DRO, namely 20ng/L (Low; L), 200ng/L (Medium; M), 2000ng/L (High; H) and 10μg/L (Super High; SH) nominal doses. Following exposure, no significant effect was observed on gonad maturation of treated and untreated mussels. The levels of progesterone (P4) and testosterone (T) were measured in mantle/gonad tissues and no significant alteration detected after exposure. However, the application of a protonic nuclear magnetic resonance (1H NMR)-based metabolomics approach enabled a comprehensive assessment of DRO effects in mussels. Specifically, 1H NMR metabolic fingerprints of digestive glands of DRO treated mussel groups were clearly separated from each other and from controls through a principal component analysis (PCA). Moreover, a number of metabolites involved in different metabolic pathways were found to significantly change in DRO-exposed mussels compared to control, suggesting the occurrence of alterations in energy metabolism, amino acids metabolism, and glycerophospholipid metabolism. Overall, despite no changes in gonad maturation and steroids levels were recorded in mussels after DRO exposure, the metabolomics approach demonstrated its effectiveness and high sensitivity in elucidating DRO-induced metabolic disturbances in marine mussels, and thus its usefulness in the environmental risk assessment of pharmaceuticals.

Significance of metabolites in the environmental risk assessment of pharmaceuticals consumed by human

The purpose of this study is to demonstrate the significance of metabolites to the ERA of human pharmaceuticals. The predicted exposure concentrations (PECs) in surface water were estimated for a total of 24 selected active pharmaceutical ingredients (APIs) and their metabolites using a life cycle based emission estimation model combined with a multimedia fate model with Monte-Carlo calculations. With the eco-toxicity data, the hazard quotients (HQs) of the metabolites were compared with those of individual parents alone.The results showed that PEC or toxicity or both of the metabolites was predicted to be higher than that of their parent APIs, which resulted in a total of 18 metabolites (from 12 parents) that have greater HQs than their parents. This result clearly demonstrated that some metabolites may potentially pose greater risk than their parent APIs in the water environment. Therefore, significance of metabolites should be carefully evaluated for monitoring strategy, priority setting, and scoping of the environmental risk assessment of APIs. The method used in the present work may serve as a pragmatic approach for the purpose of preliminary screening or priority setting of environmental risk posed by both APIs and their metabolites.

Fluoxetine Exhibits Pharmacological Effects and Trait-Based Sensitivity in a Marine Worm.

Global production of pharmacologically active compounds exceeds 100 000 tons annually, a proportion of which enters aquatic environments through patient use, improper medicine disposal, and production. These compounds are designed to have mode-of-action (MoA) effects on specific biological pathways, with potential to impact nontarget species. Here, we used MoA and trait-based approaches to quantify uptake and biological effects of fluoxetine, a selective serotonin reuptake inhibitor, in filter and deposit feeding marine worms (Hediste diversicolor). Worms exposed to 10 μg L(-1), accumulated fluoxetine with a body burden over 270 times greater than exposure concentrations, resulting in ∼10% increased coelomic fluid serotonin, a pharmacological effect. Observed effects included weight loss (up to 2% at 500 μg L(-1)), decreased feeding rate (68% at 500 μg L(-1)), and altered metabolism (oxygen consumption, ammonia excretion, and O/N from 10 μg L(-1)). Bioconcentration of fluoxetine was dependent on route of uptake, with filter feeding worms experiencing up to 130 times greater body burden ratios and increased magnitudes of effects than deposit feeders, a trait-based sensitivity likely as a consequence of fluoxetine partitioning to sediment. This study highlights how novel approaches such as MoA and trait-based methods can supplement environmental risk assessments of pharmaceuticals.

Occurrence, removal and environmental risk assessment of pharmaceuticals and personal care products in rural wastewater treatment wetlands

Rural communities in central and eastern Europe usually use constructed wetlands (CWs) to treat domestic wastewater. Effluents from these systems are regularly discharged to receiving water, resulting in a potential transfer of pharmaceuticals and personal care products (PPCPs) from sewage to the aquatic environment. In this study, the seasonal occurrence, removal and risk assessment of 32 multi-class PPCPs were investigated in three CWs from the village of south Bohemia, Czech Republic. Among the PPCPs considered, 25 compounds were detected in sewage influent, and ibuprofen, caffeine and paracetamol were the most commonly detected PPCPs. The removal efficiencies of PPCPs in the rural CWs exhibited large variability with 11–100% for anti-inflammatories, 37–99% for β-blockers and 18–95% for diuretics. The statistical results revealed significant correlations between removal efficiencies of six PPCPs and conventional water quality parameters. The ecotoxicological assessment study revealed that most of the PPCPs (except ibuprofen) in the effluent yielded low aquatic risk. This study suggested that constructed wetlands could be effective for removing PPCPs and reducing environmental risk of PPCPs discharged from rural communities into surface water systems.

Environmental Risk Assessment of Pharmaceutical Mixtures: Demands, Gaps, and Possible Bridges.

The ecotoxicological risk of pharmaceutical mixtures typically exceeds the risk of each individual compound, which calls specific attention to the fact that monitoring surveys routinely find complex pharmaceutical mixtures in various environmental compartments. However, although the body of evidence on the ecotoxicology of pharmaceutical mixtures is quite consistent, the current guidelines for the environmental risk assessment of pharmaceuticals often do not explicitly address mixture effects. Data availability and acceptable methods often limit such assessments. A tiered approach that begins with summing up individual risk quotients, i.e., the ratio between the predicted or measured environmental concentration and the predicted no effect concentration (PNEC) is therefore suggested in this paper, in order to improve the realism of the environmental risk assessment of pharmaceuticals. Additionally, the use of a mixture-specific assessment factor, as well as the classical mixture toxicity concepts of concentration addition and independent action is explored. Finally, specific attention is given to the exposure-based waiving of environmental risk assessments, as currently implemented in screening or pre-screening phases (tier 0 in Europe, categorical exclusion in the USA), since even low, individually non-toxic concentrations might combine to produce substantial mixture effects.