Pharmaceutical Pollution of the English National Parks.

England's 10 national parks are renowned for their landscapes, wildlife, and recreational value. However, surface waters in the national parks may be vulnerable to pollution from human-use chemicals, such as active pharmaceutical ingredients (APIs), because of factors like ineffective wastewater treatment, seasonal tourism, a high proportion of elderly residents, and the presence of low-flow water bodies that limit dilution. The present study determined the extent of API contamination in the English national parks by monitoring 54 APIs in 37 rivers across all national parks over two seasons. Results were compared to existing data sets for UK cities and to concentration thresholds for ecological impacts and antimicrobial resistance selection. Results revealed widespread contamination of the national parks, with APIs detected at 52 out of 54 sites and in both seasons. Thirty-one APIs were detected, with metformin, caffeine, and paracetamol showing the highest mean concentrations and cetirizine, metformin, and fexofenadine being the most frequently detected. While total API concentrations were generally lower than seen previously in UK cities, locations in the Peak District and Exmoor had higher concentrations than most city rivers. Fourteen locations had concentrations of either amitriptyline, carbamazepine, clarithromycin, diltiazem, metformin, paracetamol, or propranolol above levels of concern for fish, invertebrates, and algae or for selection for antimicrobial resistance. Therefore, API pollution of the English national parks appears to pose risks to ecological health and potentially human health through recreational water use. Given that these parks are biodiversity hotspots with protected ecosystems, there is an urgent need for improved monitoring and management of pharmaceutical pollution and pollution more generally not only in national parks in England but also in similar environments across the world. Environ Toxicol Chem 2024;00:1-14. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Are pharmaceutical residues in crops a threat to human health?

The application of biosolids, manure, and slurry onto agricultural soils and the growing use of treated wastewater in agriculture result in the introduction of human and veterinary pharmaceuticals to the environment. Once in the soil environment, pharmaceuticals may be taken up by crops, resulting in consequent human exposure to pharmaceutical residues. The potential side effects of pharmaceuticals administered in human medicine are widely documented; however, far less is known regarding the risks that arise from incidental dietary exposure. The aim of this study was to evaluate human exposure to pharmaceutical residues in crops and assess the associated risk to health for a range of pharmaceuticals frequently detected in soils. Estimated concentrations of carbamazepine, oxytetracycline, sulfamethoxazole, trimethoprim, and tetracycline in soil were used in conjunction with plant uptake and crop consumption data to estimate daily exposures to each compound. Exposure concentrations were compared to Acceptable Daily Intakes (ADIs) to determine the level of risk. Generally, exposure concentrations were lower than ADIs. The exceptions were carbamazepine, and trimethoprim and sulfamethoxazole under conservative, worst-case scenarios, where a potential risk to human health was predicted. Future research therefore needs to prioritize investigation into the health effects following exposure to these compounds from consumption of contaminated crops.

Plastic Litter Emits the Foraging Infochemical Dimethyl Sulfide after Submersion in Freshwater Rivers.

Plastic pollution is widespread throughout aquatic environments globally, with many organisms known to interact with and ingest plastic. In marine environments, microbial biofilms that form on plastic surfaces can produce the odorous compound dimethyl sulfide (DMS), which is a known foraging cue. This has been shown to increase the ingestion of plastic by some invertebrates and therefore act as a biological factor which influences the risks of plastic to marine ecosystems. In freshwater however, the production of DMS has been largely overlooked, despite the known sensitivity of some freshwater species to this compound. To address this gap, the present study analyzed the production of DMS by biofilms which formed on low-density polyethylene and polylactic acid films after 3 and 6 weeks of submersion in either a rural or an urban United Kingdom river. Using gas chromatography-mass spectrometry, the production of DMS by these biofilms was consistently identified. The amount of DMS produced varied significantly across river locations and materials, with surfaces in the urban river generally producing a stronger signal and plastics producing up to seven times more DMS than glass control surfaces. Analysis of biofilm weight and photosynthetic pigment content indicated differences in biofilm composition across conditions and suggested that DMS production was largely driven by nonphotosynthetic taxa. For the first time this work has documented the production of DMS by plastic litter after submersion in freshwater rivers. Further work is now needed to determine if, as seen in marine systems, this production of DMS can encourage the interaction of freshwater organisms with plastic litter and therefore operate as a biological risk factor in the impacts of plastic on freshwater environments. Environ Toxicol Chem 2024;43:1485-1496. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Environmental management cycles for chemicals and climate change, EMC4 : A new conceptual framework contextualizing climate and chemical risk assessment and management.

The environmental management cycles for chemicals and climate change (EMC4 ) is a suggested conceptual framework for integrating climate change aspects into chemical risk management. The interaction of climate change and chemical risk brings together complex systems that are imperfectly understood by science. Making management decisions in this context is therefore difficult and often exacerbated by a lack of data. The consequences of poor decision-making can be significant for both environmental and human health. This article reflects on the ways in which existing chemicals management systems consider climate change and proposes the EMC4 conceptual framework, which is a tool for decision-makers operating at different spatial scales. Also presented are key questions raised by the tool to help the decision-maker identify chemical risks from climate change, management options, and, importantly, the different types of actors that are instrumental in managing that risk. Case studies showing decision-making at different spatial scales are also presented highlighting the conceptual framework's applicability to multiple scales. The United Nations Environment Programme's development of an intergovernmental Science Policy Panel on Chemicals and Waste has presented an opportunity to promote and generate research highlighting the impacts of chemicals and climate change interlinkages. Integr Environ Assess Manag 2024;20:433-453. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Incorporating climate change model projections into ecological risk assessments to help inform risk management and adaptation strategies: Synthesis of a SETAC Pellston Workshop®.

The impacts of global climate change are not yet well integrated with the estimates of the impacts of chemicals on the environment. This is evidenced by the lack of consideration in national or international reports that evaluate the impacts of climate change and chemicals on ecosystems and the relatively few peer-reviewed publications that have focused on this interaction. In response, a 2011 Pellston Workshop® was held on this issue and resulted in seven publications in Environmental Toxicology and Chemistry. Yet, these publications did not move the field toward climate change and chemicals as important factors together in research or policy-making. Here, we summarize the outcomes of a second Pellston Workshop® on this topic held in 2022 that included climate scientists, environmental toxicologists, chemists, and ecological risk assessors from 14 countries and various sectors. Participants were charged with assessing where climate models can be applied to evaluating potential exposure and ecological effects at geographical and temporal scales suitable for ecological risk assessment, and thereby be incorporated into adaptive risk management strategies. We highlight results from the workshop's five publications included in the special series "Incorporating Global Climate Change into Ecological Risk Assessments: Strategies, Methods and Examples." We end this summary with the overall conclusions and recommendations from participants. Integr Environ Assess Manag 2024;20:359-366. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Uptake of Pharmaceuticals by Crops: A Systematic Review and Meta-analysis.

Studies on the uptake of pharmaceuticals from soils into crops were first conducted in the 2000s. Since then a wealth of such data has been generated, but to the best of our knowledge, these studies have not been systematically reviewed. We present a quantitative, systematic review of empirical data on the uptake of pharmaceuticals into crops. We developed a custom-made relational database on plant uptake of pharmaceuticals that contained details of the experimental design and associated results from 150 articles, spanning 173 pharmaceuticals, 78 study crops, and 8048 unique measurements. Analysis of the data in the database showed clear trends in experimental design, with lettuce being the most studied crop and carbamazepine and sulfamethoxazole being the most studied pharmaceuticals. Pharmaceutical properties were found to create the greatest range in uptake concentrations of any single variable studied. Uptake concentrations were also found to vary between crops, with relatively high uptake concentrations identified in cress, lettuce, rice, and courgette crops. An understanding of the influence of soil properties on pharmaceutical uptake was limited by a lack of information on key soil properties across the published literature. The data comparisons were inhibited by differences in quality of the different studies. Moving forward, a framework for best practice in this field is needed to maximize the value and further applications of the data produced. Environ Toxicol Chem 2023;42:2091-2104. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Caddisfly Larvae are a Driver of Plastic Litter Breakdown and Microplastic Formation in Freshwater Environments.

Plastic litter is now pervasive in the aquatic environment. Several marine and terrestrial organisms can fragment plastic with their feeding appendages, facilitating its breakdown and generating microplastics. However, similar studies with freshwater organisms are extremely limited. We explored the interactions between the caddisfly larvae Agrypnia sp. and polylactic acid (PLA) film. The use of plastic by larvae to build their protective cases was investigated, along with their ability to fragment the plastic film as they do with leaf litter. Caddisfly consistently incorporated PLA into their cases alongside leaf material. They also used their feeding appendages to rapidly fragment PLA-forming hundreds of submillimeter-sized microplastics. Although larvae showed a preference for leaf material when constructing cases, plastic use and fragmentation still occurred when leaf material was replete, indicating that this behavior is likely to occur in natural environments that are polluted with plastics. This is thought to be the first documented evidence of active plastic modification by a freshwater invertebrate and therefore reveals a previously unidentified mechanism of plastic fragmentation and microplastic formation in freshwater. Further work is now needed to determine the extent of this behavior across freshwater taxa and the potential implications for the wider ecosystem. Environ Toxicol Chem 2022;41:3058-3069. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

European scale assessment of the potential of ozonation and activated carbon treatment to reduce micropollutant emissions with wastewater.

Micropollutants (MPs) in wastewater pose a growing concern for their potential adverse effects on the receiving aquatic environment, and some countries have started requiring that wastewater treatment plants remove them to a certain extent. Broad spectrum advanced treatment processes, such as ozonation, activated carbon or their combination, are expected to yield a significant reduction in the toxicity of effluents. Here we quantify the reduction of effluent toxicity potentially achieved by implementing these advanced treatment solutions in a selection of European wastewater treatment plants. To this end, we refer to a list of "total pollution proxy substances" (TPPS) composed of 1337 chemicals commonly found in wastewater effluents according to a compilation of datasets of measured concentrations. We consider these substances as an approximation of the "chemical universe" impinging on the European wastewater system. We evaluate the fate of the TPPS in conventional and advanced treatment plants using a compilation of experimental physicochemical properties that describe their sorption, volatilization and biodegradation during activated sludge treatment, as well as known removal efficiency in ozonation and activated carbon treatment, while filling the gaps through in silico prediction models. We estimate that the discharge of micropollutants with wastewater effluents in the European Union has a cumulative MP toxicity to the environment equal to the discharge of untreated wastewater of ca. 160 million population equivalents (PE), i.e. about 30 % of the generated wastewater in the EU. If all plants above a capacity of 100,000 PE were equipped with advanced treatment, we show that this load would be reduced to about 95 million PE. In addition, implementing advanced treatment in wastewater plants above 10,000 PE discharging to water bodies with an average dilution ratio smaller than 10 would yield a widespread improvement in terms of exposure of freshwater ecosystems to micropollutants, almost halving the part of the stream network exposed to the highest toxic risks. Our analysis provides background for a cost-effectiveness appraisal of advanced treatment "at the end of the pipe", which could lead to optimized interventions. This should not be regarded as a stand-alone solution, but as a complement to policies for the control of emissions at the source for the most problematic MPs.

Assessment of the Potential Ecotoxicological Effects of Pharmaceuticals in the World's Rivers.

During their production, use, and disposal, active pharmaceutical ingredients (APIs) are released into aquatic systems. Because they are biologically active molecules, APIs have the potential to adversely affect nontarget organisms. We used the results of a global monitoring study of 61 APIs alongside available ecotoxicological and pharmacological data to assess the potential ecotoxicological effects of APIs in rivers across the world. Approximately 43.5% (461 sites) of the 1052 sampling locations monitored across 104 countries in a recent global study had concentrations of APIs of concern based on apical, nonapical, and mode of action-related endpoints. Approximately 34.1% of the 137 sampling campaigns had at least one location where concentrations were of ecotoxicological concern. Twenty-three APIs occurred at concentrations exceeding "safe" concentrations, including substances from the antidepressant, antimicrobial, antihistamine, ß-blocker, anticonvulsant, antihyperglycemic, antimalarial, antifungal, calcium channel blocker, benzodiazepine, painkiller, progestin, and lifestyle compound classes. At the most polluted sites, effects are predicted on different trophic levels and on different endpoint types. Overall, the results show that API pollution is a global problem that is likely negatively affecting the health of the world's rivers. To meet the United Nations' Sustainable Development Goals, work is urgently needed to tackle the problem and bring concentrations down to an acceptable level. Environ Toxicol Chem 2022;41:2008-2020. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Enabling forecasts of environmental exposure to chemicals in European agriculture under global change.

European agricultural development in the 21st century will be affected by a host of global changes, including climate change, changes in agricultural technologies and practices, and a shift towards a circular economy. The type and quantity of chemicals used, emitted, and cycled through agricultural systems in Europe will change, driven by shifts in the use patterns of pesticides, veterinary pharmaceuticals, reclaimed wastewater used for irrigation, and biosolids. Climate change will also impact the chemical persistence, fate, and transport processes that dictate environmental exposure. Here, we review the literature to identify research that will enable scenario-based forecasting of environmental exposures to organic chemicals in European agriculture under global change. Enabling exposure forecasts requires understanding current and possible future 1.) emissions, 2.) persistence and transformation, and 3.) fate and transport of agricultural chemicals. We discuss current knowledge in these three areas, the impact global change drivers may have on them, and we identify knowledge and data gaps that must be overcome to enable predictive scenario-based forecasts of environmental exposure under global change. Key research gaps identified are: improved understanding of relationships between global change and chemical emissions in agricultural settings; better understanding of environment-microbe interactions in the context of chemical degradation under future conditions; and better methods for downscaling climate change-driven intense precipitation events for chemical fate and transport modelling. We introduce a set of narrative Agricultural Chemical Exposure (ACE) scenarios - augmenting the IPCC's Shared Socio-economic Pathways (SSPs) - as a framework for forecasting chemical exposure in European agriculture. The proposed ACE scenarios cover a plausible range of optimistic to pessimistic 21st century development pathways. Filling the knowledge and data gaps identified within this study and using the ACE scenario approach for chemical exposure forecasting will support stakeholder planning and regulatory intervention strategies to ensure European agricultural practices develop in a sustainable manner.

One planet: one health. A call to support the initiative on a global science-policy body on chemicals and waste.

The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science-policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science-policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science-policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.

Pharmaceutical pollution of the world's rivers.

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

Interactions Between Plastic, Microbial Biofilms and Gammarus pulex: An Initial Investigation.

There is increasing evidence that microbial biofilms which form on the surface of marine plastics can increase plastics palatability, making it more attractive to organisms. The same information, however, does not exist for freshwater systems. This study observed the response of the freshwater amphipod Gammarus pulex when exposed to 3 cm-diameter discs of biofilm-covered plastic, both alone and when presented alongside its natural food. G. pulex did not fragment or consume the plastic materials, and the presence of colonised plastic in the immediate environment did not alter the amount of time organisms spent interacting with their natural food. This study provides baseline information for virgin and microbially colonised low-density polyethylene and polylactic acid film. Further studies, with other types of plastic possessing different physical properties and with different microbial biofilm compositions are now required to build further understanding of interactions between plastic, microbial biofilms, and freshwater shredding invertebrates.

Toward a Framework for Environmental Fate and Exposure Assessment of Polymers.

Development of risk-assessment methodologies for polymers is an emerging regulatory priority to prevent negative environmental impacts; however, the diversity and complexity of polymers require adaptation of existing environmental risk-assessment approaches. The present review discusses the challenges and opportunities for the fate and exposure assessment of polymers in the context of regulatory environmental risk assessment of chemicals. The review discusses the applicability and adequacy for polymers of existing fate parameters used for nonpolymeric compounds and proposes additional parameters that could inform the fate of polymers. The significance of these parameters in various stages of an exposure-assessment framework is highlighted, with classification of polymers as solid or dissolved being key for identification of those parameters most relevant to environmental fate. Considerations to address the key limitations and knowledge gaps are then identified and discussed, specifically the complexity of polymer identification, with the need for characterization of the most significant parameters for polymer grouping and prioritization; the complexity of polymer degradation in the environment, with the need to incorporate the fate and hazards of degradation products into risk assessment; the requirement for development and standardization of analytical methods for characterization of polymer fate properties and degradation products; and the need to develop exposure modeling approaches for polymers. Environ Toxicol Chem 2022;41:515-540. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

High Concentrations of Pharmaceuticals in a Nigerian River Catchment.

Pharmaceutical contamination of the environment is recognized as a global problem although most research has focused on Europe and North America to date, and there remains a dearth of information for developing countries, including those in Africa. To address this data gap, the occurrence of 37 pharmaceuticals belonging to 19 therapeutic classes was monitored in surface water and effluents in Lagos State, Southwest Nigeria. Samples were collected quarterly between April 2017 and March 2018 from 22 sites, and 26 compounds were detected at least once, many in the µg/L range. Maximum concentrations for those compounds detected ranged from 75 to 129 µg L-1 , and even mean concentrations for 13 compounds were in the order of µg L-1 . These values are among the highest ever measured globally. Sewage effluent was more important than drug manufacturing waste in polluting rivers, although there are likely to be numerous unregulated sources of effluent being discharged to rivers that require further study, including urban waste collection areas and vacuum trucks that collect effluent. Seasonal trends in the data were complex, with some compounds being found at higher concentrations in the dry season and, conversely, others being greater during the wet period; this variation potentially relates to the variety of pollution sources in the catchment. Pharmaceuticals are indispensable to human health, although their usage and discharge into the aquatic environment may lead to ecological problems and antibiotic resistance. The data we present indicate that pharmaceutical pollution of freshwaters is a serious issue in Nigeria, and management efforts are needed to improve this problem. Environ Toxicol Chem 2022;41:551-558. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Environmental contamination by pet pharmaceuticals: A hidden problem.

As the environmental risks of companion animal pharmaceuticals has been assumed to be low, currently, no data on the fate, behaviour or effect is required by the European Medicines Agency. This is in sharp contrast with what happens in farming animals, where ecotoxicological data is a pivotal part on the benefit-risk assessment for the marketing authorization of a new veterinary drug. Recently, concern about the environmental impacts from the indiscriminate prophylactic use of antiparasitic drugs in pets has arisen. Considering the notable increase of companion animals in Europe since 2010, our impression is that, effects and potential deleterious consequences of other therapeutic classes such as antimicrobials and psychotropic drugs are probably underrated. We believe that pets, as animals, should not be excluded from One Health's philosophy, and that authorities should incorporate environmental aspects in the benefit-risk assessment for drugs used in companion animals as well.

Use of a large dataset to develop new models for estimating the sorption of active pharmaceutical ingredients in soils and sediments.

Information on the sorption of active pharmaceutical ingredients (APIs) in soils and sediments is needed for assessing the environmental risks of these substances yet these data are unavailable for many APIs in use. Predictive models for estimating sorption could provide a solution. The performance of existing models is, however, often poor and most models do not account for the effects of soil/sediment properties which are known to significantly affect API sorption. Therefore, here, we use a high-quality dataset on the sorption behavior of 54 APIs in 13 soils and sediments to develop new models for estimating sorption coefficients for APIs in soils and sediments using three machine learning approaches (artificial neural network, random forest and support vector machine) and linear regression. A random forest-based model, with chemical and solid descriptors as the input, was the best performing model. Evaluation of this model using an independent sorption dataset from the literature showed that the model was able to predict sorption coefficients of 90% of the test set to within a factor of 10 of the experimental values. This new model could be invaluable in assessing the sorption behavior of molecules that have yet to be tested and in landscape-level risk assessments.

ECORISK2050: An Innovative Training Network for predicting the effects of global change on the emission, fate, effects, and risks of chemicals in aquatic ecosystems.

By 2050, the global population is predicted to reach nine billion, with almost three quarters living in cities. The road to 2050 will be marked by changes in land use, climate, and the management of water and food across the world. These global changes (GCs) will likely affect the emissions, transport, and fate of chemicals, and thus the exposure of the natural environment to chemicals. ECORISK2050 is a Marie Sklodowska-Curie Innovative Training Network that brings together an interdisciplinary consortium of academic, industry and governmental partners to deliver a new generation of scientists, with the skills required to study and manage the effects of GCs on chemical risks to the aquatic environment. The research and training goals are to: (1) assess how inputs and behaviour of chemicals from agriculture and urban environments are affected by different environmental conditions, and how different GC scenarios will drive changes in chemical risks to human and ecosystem health; (2) identify short-to-medium term adaptation and mitigation strategies, to abate unacceptable increases to risks, and (3) develop tools for use by industry and policymakers for the assessment and management of the impacts of GC-related drivers on chemical risks. This project will deliver the next generation of scientists, consultants, and industry and governmental decision-makers who have the knowledge and skillsets required to address the changing pressures associated with chemicals emitted by agricultural and urban activities, on aquatic systems on the path to 2050 and beyond.

Ecological Risk Dynamics of Pharmaceuticals in Micro-Estuary Environments.

Micro-estuarine ecosystems have a surface area <1 km2 and are abundant in Mediterranean regions. As a result of their small size, these systems are particularly vulnerable to the effects of chemical pollution. Due to the fluctuating flow conditions of base flow dominated by treated wastewater effluents and flood events transporting rural and urban non-point-source pollution, micro-estuaries are under a dynamic risk regime, consequently struggling to provide ecological services. This 2 year study explored the occurrence and risks of pharmaceutical contamination in the Alexander micro-estuary in Israel. Pharmaceuticals were detected in all samples (n = 280) at as high as 18 µg L-1 in flood events and 14 µg L-1 in base flow. The pharmaceutical mixture composition was affected by flow conditions with carbamazepine dominating the base flow and caffeine dominating flood events. The median annual risk quotients for fish, crustaceans, and algae were 19.6, 5.2, and 4.5, respectively, indicating that pharmaceuticals pose a high risk to the ecosystem. Ibuprofen, carbamazepine, and caffeine contributed most to the risk quotients. The current work highlights that micro-estuary ecosystems, like the Alexander estuary, are continuously exposed to pharmaceuticals and most likely to other pollutants, placing these ecologically important systems under an elevated risk in comparison to the more frequently studied large estuarine systems.