Mapping domestic water use to quantify water-demand and water-related contaminant exposure in a peri-urban community, Indonesia.

Water use of domestic activities was quantified by interviewing 217 people in a peri-urban community near Bandung, Indonesia. Resulting in data on domestic water demand and data needed for exposure modelling of domestic activities: drinking, cooking, brushing teeth, swimming, bathing, laundry, dishwashing, religious cleansing, washing hands and cleaning food. Average total domestic water usage was 117 l/person/day, topping the WHO guidelines for basic needs (50-100 l/person/day). This water use level is comparable with higher income countries for the same set of activities but 100% higher than water use in an Indonesian traditional rural community. The final dataset provides insight in quantity of water used for domestic activities, as well as the use-frequency, duration and water sources used. These data are scarce for Indonesia and other low-middle income countries but necessary for water demand studies and estimating risks through exposure to pathogens and emerging contaminants in human exposure modelling.

In silico ecotoxicity assessment of pharmaceutical residues in wastewater following oxidative treatment.

Advanced oxidation processes such as thermal plasma activation and UV-C/H2O2 treatment are considered as applications for the degradation of pharmaceutical residues in wastewater complementary to conventional wastewater treatment. It is supposed that direct oxidative treatment can lower the toxicity of hospital sewage water (HSW). The aim of this study was to predict the ecotoxicity for three aquatic species before and after oxidative treatment of 10 quantified pharmaceuticals in hospital sewage water. With the application of oxidative chemistry, pharmaceuticals are degraded into transformation products before reaching complete mineralization. To estimate the potential ecotoxicity for fish, Daphnia and green algae ECOSAR quantitative structure-activity relationship software was used. Structure information from pristine pharmaceuticals and their oxidative transformation products were calculated separately and in a mixture computed to determine the risk quotient (RQ). Calculated mixture toxicities for 10 compounds found in untreated HSW resulted in moderate-high RQ predictions for all three aquatic species. Compared to untreated HSW, 30-min treatment with thermal plasma activation or UV-C/H2O2 resulted in lowered RQs. For the expected transformation products originating from fluoxetine, cyclophosphamide and acetaminophen increased RQs were predicted. Prolongation of thermal plasma oxidation up to 120 min predicted low-moderate toxicity in all target species. It is anticipated that further degradation of oxidative transformation products will end in less toxic aliphatic and carboxylic acid products. Predicted RQs after UV-C/H2O2 treatment turned out to be still moderate-high. In conclusion, in silico extrapolation of experimental findings can provide useful predicted estimates of mixture toxicity. However due to the complex composition of wastewater this in silico approach is a first step to screen for ecotoxicity. It is recommendable to confirm these predictions with ecotoxic bioassays.

Prioritisation of data-poor pharmaceuticals for empirical testing and environmental risk assessment.

There are more than 3,500 active pharmaceutical ingredients (APIs) on the global market for human and veterinary use. Residues of these APIs eventually reach the aquatic environment. Although an environmental risk assessment (ERA) for marketing authorization applications of medicinal products is mandatory in the European Union since 2006, an ERA is lacking for most medicines approved prior to 2006 (legacy APIs). Since it is unfeasible to perform extensive ERA tests for all these legacy APIs, there is a need for prioritization of testing based on the limited data available. Prioritized APIs can then be further investigated to estimate their environmental risk in more detail. In this study, we prioritized more than 1,000 APIs used in Europe based on their predicted risk for aquatic freshwater ecosystems. We determined their risk by combining an exposure estimate (Measured or Predicted Environmental Concentration; MEC or PEC, respectively) with a Predicted No Effect Concentration (PNEC). We developed several procedures to combine the limited empirical data available with in silico data, resulting in multiple API rankings varying in data needs and level of conservativeness. In comparing empirical with in silico data, our analysis confirmed that the PEC estimated with the default parameters used by the European Medicines Agency often - but not always - represents a worst-case scenario. Comparing the ecotoxicological data for the three main taxonomic groups, we found that fish represents the most sensitive species group for most of the APIs in our list. We furthermore show that the use of in silico tools can result in a substantial underestimation of the ecotoxicity of APIs. After combining the different exposure and effect estimates into four risk rankings, the top-ranking APIs were further screened for availability of ecotoxicity data in data repositories. This ultimately resulted in the prioritization of 15 APIs for further ecotoxicological testing and/or exposure assessment.

Characterization of urban sources of antibiotics and antibiotic-resistance genes in a Dutch sewer catchment.

A one year study was conducted in the city of Nijmegen, The Netherlands, to characterize various urban sources of antibiotics and antibiotic resistant genes (ARGs) in wastewater within a single sewer catchment. Prevalence of ermB, tet(W), sul1, sul2, intl1, and 16S rRNA gene was determined at 10 locations within the city. Sampling locations included a nursing home, a student residence, a hospital and an industrial area, among others. Wastewater concentrations of 23 antibiotics were measured using passive sampling. Additionally, excreted loads of 22 antibiotics were estimated based on ambulatory prescription and clinical usage data. Genes sul1 and intl1 were most abundant across most locations. Ciprofloxacin and amoxicillin together contributed over 92 % of the total estimated antibiotic selective pressure at all sampling points. The present study highlights the prominent role that hospitals can have in the prevalence and proliferation of ARGs in urban wastewater. Furthermore, results suggest that even short-term changes in the therapeutic regimen prescribed in hospitals may translate into shifting ARG abundance patterns in hospital wastewater. The methods applied present an opportunity to identify emission hotspots and prioritize intervention options to limit ARG spread from urban wastewater to the environment.

Tyre granulate on the loose; How much escapes the turf? A systematic literature review.

Tyre granulate used as infill for artificial turf is hailed by some as a good example of reuse, while others see it as a baleful means to dispose of discarded tyres. Because the particles are applied loosely to the surface, they will inevitably disperse into the environment. The possible environmental and health impacts of the particles are a source of societal concern. In response to this, policies to limit particle losses are being developed at the European level. To make informed decisions, data on the quantity of tyre granulate released into the environment are required. So far, however, there are no systematic reviews on or estimates of these losses. The aim of the present study was to identify the various pathways through which infill leaves a football turf and, subsequently, to estimate the quantity of infill leaving the turf by each of these pathways. Data on the pathways including the associated volumes were collected in a systematic literature review following the PRISMA method. The quality of the evidence reported in the retrieved literature was assessed using the GRADE method. The resulting pathways and corresponding quantities were captured in a mass balance. This study estimates that, without mitigation measures, approximately 950 kg/year (min. 570 kg/year, max. 2280 kg/year) of infill leaves the surface of an average artificial football turf via known pathways. Clearing snow can result in an additional loss of 830 kg/year (min. 200 kg/year, max. 2760 kg/year) of infill material. To mitigate the dispersion of infill, one could focus on snow removal, brushing and granulate picked up by players. Mitigation measures for these pathways are well-established and relatively easy to implement and maintain. Although the amount of granulate picked up from the turf by players is relatively small, the measure will promote environmental awareness among the players.

Predicting and improving the microbial removal of organic micropollutants during wastewater treatment: A review.

Organic micropollutants (OMPs) consist of widely used chemicals such as pharmaceuticals and pesticides that can persist in surface and groundwaters at low concentrations (ng/L to µg/L) for a long time. The presence of OMPs in water can disrupt aquatic ecosystems and threaten the quality of drinking water sources. Wastewater treatment plants (WWTPs) rely on microorganisms to remove major nutrients from water, but their effectiveness at removing OMPs varies. Low removal efficiency might be the result of low concentrations, inherent stable chemical structures of OMPs, or suboptimal conditions in WWTPs. In this review, we discuss these factors, with special emphasis on the ongoing adaptation of microorganisms to degrade OMPs. Finally, recommendations are drawn to improve the prediction of OMP removal in WWTPs and to optimize the design of new microbial treatment strategies. OMP removal seems to be concentration-, compound-, and process-dependent, which poses a great complexity to develop accurate prediction models and effective microbial processes targeting all OMPs.

Quantification and characterization of macro- and mesoplastic items in the water column of the river Waal.

Although studies on plastic concentrations mainly focus on the marine environment, recently, an increasing number of studies point out environmental consequences in freshwater environments around the world. However, there still is a paucity of field data on the abundance of riverine plastic items, in particular in the water column. In this study, we provide an overview of macro- and mesoplastic concentrations, categories, ages, and origin over several years in the water column of the river Waal, in the Netherlands. The river water column was passively sampled at two selected locations using a stow net at very low and low discharges (range 537 - 1345 m3.s-1). The most dominant macro- and mesoplastic categories were 'Miscellaneous plastic waste', including "Plastic film 2.5 - 50 cm (soft)" and "Plastic film 0 - 2.5 cm (soft)" as main categories. Macro- and mesoplastic categories were found to show limited variability during several years of monitoring. The mean macroplastic concentration (± SD) ranged between 2.2 × 10-3 ± 0.001 and 7.4 × 10-3 ± 0.003 particles.m-3 for October 2020 and November 2018, respectively. In 2020, the plastic concentrations showed a sharp decrease compared to the previous years, most likely as a consequence of the COVID-19 crisis. The origin of the plastics (e.g., countries) also showed little variability during monitoring. The consistency of several characteristics of the collected plastic suggests that the same sources were responsible for the macro- and mesoplastic input into the river Waal during low discharges and over multiple years. We present the first temporal assessment of macro- and mesoplastic concentrations and composition in the water column of the river Waal. The outcome of the current study can be used to support the development of management measures by decision makers.

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.

Human health risk assessment of pharmaceuticals in the European Vecht River.

Active pharmaceutical ingredients (APIs) can reach surface waters used for drinking water extraction and recreational activities, such as swimming and fishing. The aim of the present study was to systematically assess the lifetime human health risks posed by 15 individual APIs and their mixtures occurring in the German-Dutch transboundary Vecht River. An exposure model was developed and used to assess the combined risks of oral and dermal exposure under a variety of exposure conditions. A total of 4500 API uptake values and 165 lifetime risk values were estimated for 15 and 11 APIs, respectively. Overall, the lifetime human health risks posed by the APIs and their mixtures based on modeling results were deemed acceptable under typical exposure conditions. Under very extreme environmental conditions and human behavior, API mixture risks were of potential concern while the risks of individual APIs were negligible, with a few exceptions. The antibiotic doxycycline and analgesic phenazone showed the highest and lowest risks, respectively. The study did not evaluate the potential risks caused by metabolite compounds. Recommendations for water managers are provided to help improve the accuracy and utility of human health risk assessments of pharmaceuticals. Integr Environ Assess Manag 2022;18:1639-1654. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Ibuprofen exposure in Europe; ePiE as an alternative to costly environmental monitoring.

The EU Water Framework Directive and Priority Substance Directive provide a framework to identify substances that potentially pose a risk to surface waters and provide a legal basis whereby member states are required to monitor and comply with environmental quality standards (EQSs) set for those substances. The cost and effort to continuously measure and analyse real world concentrations in all water bodies across Europe are high. Establishing the reliability of environmental exposure models to predict concentrations of priority substances is key, both to fill data gaps left by monitoring campaigns, and to predict the outcomes of actions that might be taken to reduce exposure. In this study, we aimed to validate the ePiE model for the pharmaceutical ibuprofen by comparing predictions made using the best possible consumption data with measured river concentrations. The results demonstrate that the ePiE model makes useful, conservative exposure predictions for ibuprofen, typically within a factor of 3 of mean measured values. This exercise was performed across a number of basins within Europe, representative of varying conditions, including consumption rates, population densities and climates. Incorporating specific information pertaining to the basin or country being assessed, such as custom WWTP removal rates, was found to improve the realism and accuracy of predictions. We found that the extrapolation of consumption data between countries should be kept to a minimum when modelling the exposure of pharmaceuticals, with the per capita consumption of ibuprofen varying by nearly a factor of 10.

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

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

Do initial concentration and activated sludge seasonality affect pharmaceutical biotransformation rate constants?

Pharmaceuticals find their way to the aquatic environment via wastewater treatment plants (WWTPs). Biotransformation plays an important role in mitigating environmental risks; however, a mechanistic understanding of involved processes is limited. The aim of this study was to evaluate potential relationships between first-order biotransformation rate constants (kb) of nine pharmaceuticals and initial concentration of the selected compounds, and sampling season of the used activated sludge inocula. Four-day bottle experiments were performed with activated sludge from WWTP Groesbeek (The Netherlands) of two different seasons, summer and winter, spiked with two environmentally relevant concentrations (3 and 30 nM) of pharmaceuticals. Concentrations of the compounds were measured by LC-MS/MS, microbial community composition was assessed by 16S rRNA gene amplicon sequencing, and kb values were calculated. The biodegradable pharmaceuticals were acetaminophen, metformin, metoprolol, terbutaline, and phenazone (ranked from high to low biotransformation rates). Carbamazepine, diatrizoic acid, diclofenac, and fluoxetine were not converted. Summer and winter inocula did not show significant differences in microbial community composition, but resulted in a slightly different kb for some pharmaceuticals. Likely microbial activity was responsible instead of community composition. In the same inoculum, different kb values were measured, depending on initial concentration. In general, biodegradable compounds had a higher kb when the initial concentration was higher. This demonstrates that Michealis-Menten kinetic theory has shortcomings for some pharmaceuticals at low, environmentally relevant concentrations and that the pharmaceutical concentration should be taken into account when measuring the kb in order to reliably predict the fate of pharmaceuticals in the WWTP. KEY POINTS: • Biotransformation and sorption of pharmaceuticals were assessed in activated sludge. • Higher initial concentrations resulted in higher biotransformation rate constants for biodegradable pharmaceuticals. • Summer and winter inocula produced slightly different biotransformation rate constants although microbial community composition did not significantly change.

Internal and Maternal Distribution of Persistent Organic Pollutants in Sea Turtle Tissues: A Meta-Analysis.

We aimed to identify patterns in the internal distribution of persistent organic pollutants (POPs) and assess contributing factors using sea turtles and their offspring as a case study of a long-lived wildlife species. We systematically synthesized 40 years of data and developed a lipid database to test whether lipid-normalized POP concentrations are equal among tissues as expected under steady state for lipophilic compounds. Results supported equal partitioning among tissues with high blood flow or perfusion including the heart, kidney, muscle, and lung. Observed differences in the brain, fat, and blood plasma, however, suggest the physiological influence of the blood-brain barrier, limited perfusion, and protein content, respectively. Polybrominated diphenyl ethers partitioned comparably to legacy POPs. Polycyclic aromatic hydrocarbons, meanwhile, partitioned more into the lung, colon, and muscle compared to the liver under chronic and acute field exposure. Partitioning ratios of individual POPs among tissues were significantly related to the lipophilicity of compounds (as estimated by Kow) in half of the observed cases, and significant differences between juveniles and adults underscore physiological differences across life stages. The comprehensive tissue partitioning patterns presented here provide a quantitative basis to support comparative assessments of POP pollution derived from biomonitoring among multiple tissues.

The importance of over-the-counter-sales and product format in the environmental exposure assessment of active pharmaceutical ingredients.

When assessing the environmental exposure of active pharmaceutical ingredients (APIs), the mass contributed from over the counter (OTC) sales are often not included due to difficulty obtaining this data and topical formats are overlooked completely. This study presents a comprehensive approach, investigating the significance of OTC and topical applications as sources of API releases to wastewater, in addition to temporal and subnational variations in use in the UK. The study provides methods to obtain and make use of OTC sales data which can be applied widely. The calculated releases to wastewater compared well with influent concentrations measured at several UK wastewater treatment plants (WWTPs). Consistent overestimation was observed, attributed to a number of factors, including in-sewer removal. OTC sales were found to make up a large proportion of the mass of ibuprofen (76%) and diclofenac (35%) consumed and topical formats were also found to be vital, contributing disproportionately to wastewater loadings per unit mass of ibuprofen and diclofenac used (43% and 99% of the total mass released, respectively). Releases of the APIs investigated did not vary temporally, but regional variation was significant and where possible should be considered for the most accurate exposure assessment of pharmaceuticals.

Simulating changes in polar bear subpopulation growth rate due to legacy persistent organic pollutants - Temporal and spatial trends.

Although atmospheric concentrations of many conventional persistent organic pollutants (POPs) have decreased in the Arctic over the past few decades, levels of most POPs and mercury remain high since the 1990s or start to increase again in Arctic areas, especially polar bears. So far, studies generally focused on individual effects of POPs, and do not directly link POP concentrations in prey species to population-specific parameters. In this study we therefore aimed to estimate the effect of legacy POPs and mercury on population growth rate of nineteen polar bear subpopulations. We modelled population development in three scenarios, based on species sensitivity distributions (SSDs) derived for POPs based on ecotoxicity data for endothermic species. In the first scenario, ecotoxicity data for polar bears were based on the HC50 (the concentration at which 50% of the species is affected). The other two scenarios were based on the HC5 and HC95. Considerable variation in effects of POPs could be observed among the scenarios. In our intermediate scenario, we predicted subpopulation decline for ten out of 15 polar bear subpopulations. The estimated population growth rate was least reduced in Gulf of Boothia and Foxe Basin. On average, PCB concentrations in prey (in µg/g toxic equivalency (TEQ)) posed the largest threat to polar bear subpopulations, with negative modelled population growth rates for the majority of subpopulations. We did not find a correlation between modelled population changes and monitored population trends for the majority of chemical-subpopulation combinations. Modelled population growth rates increased over time, implying a decreasing effect of PCBs, DDTs, and mercury. Polar bear subpopulations are reportedly still declining in four out of the seven subpopulations for which sufficient long-term monitoring data is available, as reported by the IUCN-PBSG. This implies that other emerging pollutants or other anthropogenic stressors may affect polar bear subpopulations.

Bioconcentration of Organotin Cations during Molting Inhibits Heterocypris incongruens Growth.

The densely populated North Sea region encompasses catchments of rivers such as Scheldt and Meuse. Herein, agricultural, industrial, and household chemicals are emitted, transported by water, and deposited in sediments, posing ecological risks. Though sediment monitoring is often costly and time-intensive, modeling its toxicity to biota has received little attention. Due to high complexity of interacting variables that induce overall toxicity, monitoring data only sporadically validates current models. Via a range of concepts, we related bio-physicochemical constituents of sediment in Flanders to results from toxicity bioassays performed on the ostracod Heterocypris incongruens. Depending on the water body, we explain up to 90% of the variance in H. incongruens growth. Though variable across Flanders' main water bodies, organotin cations and ammonia dominate the observed toxicity according to toxic unit (TU) assessments. Approximately 10% relates to testing conditions/setups, species variabilities, incoherently documented pollutant concentrations, and/or bio-physicochemical sediment properties. We elucidated the influence of organotin cations and ammonia relative to other metal(oxides) and biocides. Surprisingly, the tributylin cation appeared ∼1000 times more toxic to H. incongruens as compared to "single-substance" bioassays for similar species. We inferred indirect mixture effects between organotin, ammonia, and phosphate. Via chemical speciation calculations, we observed strong physicochemical and biological interactions between phosphate and organotin cations. These interactions enhance bioconcentration and explain the elevated toxicity of organotin cations. Our study aids water managers and policy makers to interpret monitoring data on a mechanistic basis. As sampled sediments differ, future modeling requires more emphasis on characterizing and parametrizing the interactions between bioassay constituents. We envision that this will aid in bridging the gap between testing in the laboratory and field observations.

Environmental prioritization of pesticide in the Upper Citarum River Basin, Indonesia, using predicted and measured concentrations.

A novel screening method was developed to prioritize aquatic and human health risks of pesticides based on usage data, runoff modelling and effect prediction. An important asset of this new method is that it does not require measured concentration data, which are often unavailable or difficult to obtain in low- and middle-income countries like Indonesia. The method was applied to prioritize 31 agricultural pesticides used in the Upper Citarum River Basin in West Java, Indonesia. Ranking of pesticides based on predicted concentrations generally showed good agreement with ranking based on concentrations measured by passive sampling. The individual pesticide intake through the consumption of river water was predicted to cause negligible human health risks, but substantial aquatic risks (i.e. PEC/PNEC >1) were predicted for profenofos (5.2.E+01), propineb (3.6.E+01), chlorpyrifos (2.6.E+01), carbofuran (1.7.E+01), imidacloprid (9.4.E+00), methomyl (7.6.E+00) and chlorantraniliprole (3.6.E+00). In order to protect the aquatic environment, water managers are advised to take measures to reduce the use and runoff of these pesticides in the UCRB. The screening assessment can be further refined by performing additional effect studies for some pesticides, pesticide mixtures and validation of the predicted water concentrations by targeted measurements.

Disentanglement of the chemical, physical, and biological processes aids the development of quantitative structure-biodegradation relationships for aerobic wastewater treatment.

Attenuation of organic compounds in sewage treatment plants (STPs) is affected by a complex interplay between chemical (e.g. ionization, hydrolysis), physical (e.g. sorption, volatilization), and biological (e.g. biodegradation, microbial acclimation) processes. These effects should be accounted for individually, in order to develop predictive cheminformatics tools for STPs. Using measured data from 70 STPs in the Netherlands for 69 chemicals (pharmaceuticals, herbicides, etc.), we highlighted the influences of 1) chemical ionization, 2) sorption to sludge, and 3) acclimation of the microbial consortia on the primary removal of chemicals. We used semi-empirical corrections for each of these influences to deduce biodegradation rate constants upon which quantitative structure-biodegradation relationships (QSBRs) were developed. As shown by a global QSBR, biodegradation in STPs generally relates to structural complexity, size, energetics, and charge distribution. Statistics of the global QSBR were reasonable, being R2training=0.69 (training set of 51 compounds) and R2validation=0.50 (validation set of 18 compounds). Class-specific QSBRs utilized electronic properties potentially relating to rate-limiting enzymatic steps. For class-specific QSBRs, values of R2 of in between 0.7 and 0.8 were obtained. With caution, environmental risk assessment methodologies may apply these models to estimate biodegradation rates for 'data-poor' compounds. The approach also highlights 'meta data' on STP operational parameters needed to develop QSBRs of better predictability in the future.

Reliable and representative in silico predictions of freshwater ecotoxicological hazardous concentrations.

A reliable quantification of the potential effects of chemicals on freshwater ecosystems requires ecotoxicological response data for a large set of species which is typically not available in practice. In this study, we propose a method to estimate hazardous concentrations (HCs) of chemicals on freshwater ecosystems by combining two in silico approaches: quantitative structure activity relationships (QSARs) and interspecies correlation estimation (ICE) models. We illustrate the principle of our QSAR-ICE method by quantifying the HCs of 51 chemicals at which 50% and 5% of all species are exposed above the concentration causing acute effects. We assessed the bias of the HCs, defined as the ratio of the HC based on measured ecotoxicity data and the HC based on in silico data, as well as the statistical uncertainty, defined as the ratio of the 95th and 5th percentile of the HC. Our QSAR-ICE method resulted in a bias that was comparable to the use of measured data for three species, as commonly used in effect assessments: the average bias of the QSAR-ICE HC50 was 1.2 and of the HC5 2.3 compared to 1.2 when measured data for three species were used for both HCs. We also found that extreme statistical uncertainties (>105) are commonly avoided in the HCs derived with the QSAR-ICE method compared to the use of three measurements with statistical uncertainties up to 1012. We demonstrated the applicability of our QSAR-ICE approach by deriving HC50s for 1,223 out of the 3,077 organic chemicals of the USEtox database. We conclude that our QSAR-ICE method can be used to determine HCs without the need for additional in vivo testing to help prioritise which chemicals with no or few ecotoxicity data require more thorough assessment.

Risk-management tool for environmental prioritization of pharmaceuticals based on emissions from hospitals.

Over the past decade, the health care sector has become increasingly aware of the impact of pharmaceutical emissions to the environment. Yet, it remains unclear which compounds are the most relevant to address and at what point emission control is most effective. This study presents a modelling framework to prioritize pharmaceuticals based on their relative risks for aquatic organisms, using purchase and prescription data from hospitals. The framework consists of an emission prediction module and a risk prioritization module. The emission prediction module accounts for three different routes of intake (oral, intravenous, rectal), for non-patient consumption, and for delayed athome excretion due to relatively long half-lives or prescription durations of selected pharmaceuticals. We showcase the modelling framework with 16 pharmaceuticals administered at two Dutch academic hospitals. Predictions were validated with experimental data from passive sampling in the sewer system. With the exception of metformin, all predictions were within a factor of 10 from measurements. The risk prioritization module ranks each pharmaceutical based on its predicted relative risk for aquatic organisms. The resulting prioritization suggests that emission mitigation strategies should mainly focus on antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs).