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.

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.

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.

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.

Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals.

Pharmaceuticals are ubiquitous in the natural environment with concentrations expected to rise as human population increases. Environmental risk assessments are available for a small portion of pharmaceuticals in use, raising concerns over the potential risks posed by other drugs that have little or no data. With >1900 active pharmaceutical ingredients in use, it would be a major task to test all of the compounds with little or no data. Desk-based prioritization studies provide a potential solution by identifying those substances that are likely to pose the greatest risk to the environment and which, therefore, need to be considered a priority for further study. The aim of this review was to (1) provide an overview of different prioritization exercises performed for pharmaceuticals in the environment and the results obtained; and (2) propose a new holistic risk-based prioritization framework for drugs in the environment. The suggested models to underpin this framework are discussed in terms of validity and applicability. The availability of data required to run the models was assessed and data gaps identified. The implementation of this framework may harmonize pharmaceutical prioritization efforts and ensure that, in the future, experimental resources are focused on molecules, endpoints, and environmental compartments that are biologically relevant.

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.

The Response of Lemna minor to Mixtures of Pesticides That Are Commonly Used in Thailand.

In the field, aquatic organisms are exposed to multiple contaminants rather than to single compounds. It is therefore important to understand the toxic interactions of co-occurring substances in the environment. The aim of the study was to assess the effects of individual herbicides (atrazine, 2,4-D, alachlor and paraquat) that are commonly used in Thailand and their mixtures on Lemna minor. Plants were exposed to individual and binary mixtures for 7 days and the effects on plant growth rate were assesed based on frond area measurements. Experimental observations of mixture toxicity were compared with predictions based on single herbicide exposure data using concentration addition and independent action models. The single compound studies showed that paraquat and alachlor were most toxic to L. minor, followed by atrazine and then 2,4-D. For the mixtures, atrazine with 2,4-D appeared to act antagonistically, whereas alachlor and paraquat showed synergism.

Novel Approach for Characterizing pH-Dependent Uptake of Ionizable Chemicals in Aquatic Organisms.

Here, we present and evaluate a combined experimental and modeling approach for characterizing the uptake of ionizable chemicals from water and sediments into aquatic organisms under different pH conditions. We illustrate and evaluate the approach for two pharmaceuticals (diclofenac and fluoxetine) and one personal care product ingredient (triclosan) for the oligochaete Lumbriculus variegatus. Initially, experimental data on the uptake of the three chemicals at two pH values were fitted using a toxicokinetic model to derive uptake and depuration constants for the neutral and ionized species of each molecule. The derived constants were then used to predict uptake from water and sediment for other pH conditions. Evaluation of predictions against corresponding experimental data showed good predictions of uptake for all test chemicals from water for different pH conditions and reasonable predictions of uptake of fluoxetine and diclofenac from a sediment. Predictions demonstrated that the level of uptake of the study chemicals, across pH ranges in European streams, could differ by up to a factor of 3035. Overall, the approach could be extremely useful for assessing internal exposure of aquatic organisms across landscapes with differing pH. This could help support better characterization of the risks of ionizable chemicals in the aquatic environment.

Assessment of the Risks of Mixtures of Major Use Veterinary Antibiotics in European Surface Waters.

Effects of single veterinary antibiotics on a range of aquatic organisms have been explored in many studies. In reality, surface waters will be exposed to mixtures of these substances. In this study, we present an approach for establishing risks of antibiotic mixtures to surface waters and illustrate this by assessing risks of mixtures of three major use antibiotics (trimethoprim, tylosin, and lincomycin) to algal and cyanobacterial species in European surface waters. Ecotoxicity tests were initially performed to assess the combined effects of the antibiotics to the cyanobacteria Anabaena flos-aquae. The results were used to evaluate two mixture prediction models: concentration addition (CA) and independent action (IA). The CA model performed best at predicting the toxicity of the mixture with the experimental 96 h EC50 for the antibiotic mixture being 0.248 µmol/L compared to the CA predicted EC50 of 0.21 µmol/L. The CA model was therefore used alongside predictions of exposure for different European scenarios and estimations of hazards obtained from species sensitivity distributions to estimate risks of mixtures of the three antibiotics. Risk quotients for the different scenarios ranged from 0.066 to 385 indicating that the combination of three substances could be causing adverse impacts on algal communities in European surface waters. This could have important implications for primary production and nutrient cycling. Tylosin contributed most to the risk followed by lincomycin and trimethoprim. While we have explored only three antibiotics, the combined experimental and modeling approach could readily be applied to the wider range of antibiotics that are in use.

Antibiotics and Antibiotic Resistance in Agroecosystems: State of the Science.

We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly summarized, and key knowledge gaps are highlighted. A lack of quantitative estimates of human exposure to environmental bacteria, in general, and antibiotic-resistant bacteria, specifically, is a significant data gap hindering the assessment of effects on human health. The contribution of horizontal gene transfer to resistance in the environment and conditions that might foster the horizontal transfer of antibiotic resistance genes into human pathogens also need further research. Existing research has focused heavily on human health effects, with relatively little known about the effects of antibiotics and antibiotic resistance on natural and agricultural ecosystems. The proposed causal model is used to elucidate gaps in knowledge that must be addressed by the research community and may provide a useful starting point for the design and analysis of future research efforts.

Effects of Antibiotics on the Growth and Physiology of Chlorophytes, Cyanobacteria, and a Diatom.

The occurrence of antibiotics in surface waters has been reported worldwide with concentrations ranging from ng L-1 to low µg L-1 levels. During environmental risk assessments, effects of antibiotics on algal species are assessed using standard test protocols (e.g., the OECD 201 guideline), where the cell number endpoint is used as a surrogate for growth. However, the use of photosynthetic related endpoints, such as oxygen evolution rate, and the assessment of effects on algal pigments could help to inform our understanding of the impacts of antibiotics on algal species. This study explored the effects of three major usage antibiotics (tylosin, lincomycin, and trimethoprim) on the growth and physiology of two chlorophytes (Desmodesmus subspicatus and Pseudokirchneriella subcapitata), a cyanobacteria (Anabaena flos-aquae), and a diatom (Navicula pelliculosa) using a battery of parameters, including cell density, oxygen evolution rate, total chlorophyll content, carotenoids, and the irradiance-photosynthesis relationship. The results indicated that photosynthesis of chlorophytes was a more sensitive endpoint than growth (i.e., EC50 derived based on the effects of tylosin on the growth of D. subspicatus was 38.27 µmol L-1 compared with an EC50 of 17.6 µmol L-1 based on photosynthetic rate), but the situation was reversed when testing cyanobacteria and the diatom (i.e., EC50 derived based on the effects of tylosin on the growth of A. flos-aquae was 0.06 µmol L-1; EC50 0.33 µmol L-1 based on photosynthetic rate). The pigment contents of algal cells were affected by the three antibiotics for D. subspicatus. However, in some cases, pigment content was stimulated for P. subcapitata, N. pelliculosa, and A. flos-aquae. The light utilization efficiency of chlorophytes and diatom was decreased markedly in the presence of antibiotics. The results demonstrated that the integration of these additional endpoints into existing standardised protocols could provide useful insights into the impacts of antibiotics on algal species.

Evaluation of a Novel Approach for Reducing Emissions of Pharmaceuticals to the Environment.

Increased interest over the levels of pharmaceuticals detected in the environment has led to the need for new approaches to manage their emissions. Inappropriate disposal of unused and waste medicines and release from manufacturing plants are believed to be important pathways for pharmaceuticals entering the environment. In situ treatment technologies, which can be used on-site in pharmacies, hospitals, clinics, and at manufacturing plants, might provide a solution. In this study we explored the use of Pyropure, a microscale combined pyrolysis and gasification in situ treatment system for destroying pharmaceutical wastes. This involved selecting 17 pharmaceuticals, including 14 of the most thermally stable compounds currently in use and three of high environmental concern to determine the technology's success in waste destruction. Treatment simulation studies were done on three different waste types and liquid, solid, and gaseous emissions from the process were analyzed for parent pharmaceutical and known active transformation products. Gaseous emissions were also analyzed for NOx, particulates, dioxins, furans, and metals. Results suggest that Pyropure is an effective treatment process for pharmaceutical wastes: over 99 % of each study pharmaceutical was destroyed by the system without known active transformation products being formed during the treatment process. Emissions of the other gaseous air pollutants were within acceptable levels. Future uptake of the system, or similar in situ treatment approaches, by clinics, pharmacists, and manufacturers could help to reduce the levels of pharmaceuticals in the environment and reduce the economic and environmental costs of current waste management practices.

Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days exposure to spiked soil. Bioconcentration factors (BCFs) ranged between 1.72 and 29.83 for L. terrestris and 1.14 and 63.03 for E. fetida. For carbamazepine and diclofenac, BCFs were similar whereas for fluoxetine and orlistat, BCFs in E. fetida were more than double those seen in L. terrestris. Results indicate that uptake into earthworms cannot be generalised between species and that the influence of species traits can vary depending on the nature of the study chemical.

A uniform measurement expression for cross method comparison of nanoparticle aggregate size distributions.

Available measurement methods for nanomaterials are based on very different measurement principles and hence produce different values when used on aggregated nanoparticle dispersions. This paper provides a solution for relating measurements of nanomaterials comprised of nanoparticle aggregates determined by different techniques using a uniform expression of a mass equivalent diameter (MED). The obtained solution is used to transform into MED the size distributions of the same sample of synthetic amorphous silica (nanomaterial comprising aggregated nanoparticles) measured by six different techniques: scanning electron microscopy in both high vacuum (SEM) and liquid cell setup (Wet-SEM); gas-phase electrophoretic mobility molecular analyzer (GEMMA); centrifugal liquid sedimentation (CLS); nanoparticle tracking analysis (NTA); and asymmetric flow field flow fractionation with inductively coupled plasma mass spectrometry detection (AF4-ICP-MS). Transformed size distributions are then compared between the methods and conclusions drawn on methods' measurement accuracy, limits of detection and quantification related to the synthetic amorphous silca's size. Two out of the six tested methods (GEMMA and AF4-ICP-MS) cross validate the MED distributions between each other, providing a true measurement. The measurement accuracy of other four techniques is shown to be compromised either by the high limit of detection and quantification (CLS, NTA, Wet-SEM) or the sample preparation that is biased by increased retention of smaller nanomaterials (SEM). This study thereby presents a successful and conclusive cross-method comparison of size distribution measurements of aggregated nanomaterials. The authors recommend the uniform MED size expression for application in nanomaterial risk assessment studies and clarifications in current regulations and definitions concerning nanomaterials.

Minimised bioconcentration tests: a useful tool for assessing chemical uptake into terrestrial and aquatic invertebrates?

Current guidelines for determining bioconcentration factors (BCF) and uptake and depuration rate constants require labor intensive studies with large numbers of organisms. A minimized approach has recently been proposed for fish BCF studies but its applicability to other taxonomic groups is unknown. In this study, we therefore evaluate the use of the minimized approach for estimating BCF and uptake and depuration rate constants for chemicals in aquatic and terrestrial invertebrates. Data from a range of previous BCF studies were resampled to calculate BCFs and rate constants using the minimized method. The resulting values were then compared to values obtained using full study designs. Results demonstrated a good correlation for uptake rate constants, a poor correlation for depuration rate constants and a very good correlation between the BCFs obtained using the traditional and minimized approach for a variety of organic compounds. The minimized approach therefore has merit in deriving bioconcentration factors and uptake rate constants but may not be appropriate for deriving depuration rate constants for use in, for example, toxico-kinetic toxico-dynamic modeling. The approach uses up to 70% fewer organisms, requires less labor and has lower analytical costs. The minimized design therefore could be a valuable approach for running large multifactorial studies to assess bioconcentration of the plethora of chemicals that occur in the environment into the many taxonomic groups that occur in the environment. The approach should therefore help in accelerating the development of our understanding of factors and processes affecting uptake of chemicals into organisms in the environment.

Fate and uptake of pharmaceuticals in soil-earthworm systems.

Pharmaceuticals present a potential threat to soil organisms, yet our understanding of their fate and uptake in soil systems is limited. This study therefore investigated the fate and uptake of (14)C-labeled carbamazepine, diclofenac, fluoxetine, and orlistat in soil-earthworm systems. Sorption coefficients increased in the order of carbamazepine < diclofenac < fluoxetine < orlistat. Dissipation of (14)C varied by compound, and for orlistat, there was evidence of formation of nonextractable residues. Uptake of (14)C was seen for all compounds. Depuration studies showed complete elimination of (14)C for carbamazepine and fluoxetine treatments and partial elimination for orlistat and diclofenac, with greater than 30% of the (14)C remaining in the tissue at the end of the experiment. Pore-water-based bioconcentration factors (BCFs), based on uptake and elimination of (14)C, increased in the order carbamazepine < diclofenac < fluoxetine and orlistat. Liquid chromatography-tandem mass spectrometry and liquid chromatography-Fourier transform mass spectrometry indicated that the observed uptake in the fluoxetine and carbamazepine treatments was due to the parent compounds but that diclofenac was degraded in the test system so uptake was due to unidentifiable transformation products. Comparison of our data with outputs of quantitative structure-activity relationships for estimating BCFs in worms showed that these models tend to overestimate pharmaceutical BCFs so new models are needed.

Occurrence, degradation, and effect of polymer-based materials in the environment.

There is now a plethora of polymer-based materials (PBMs) on the market, because of the increasing demand for cheaper consumable goods, and light-weight industrial materials. Each PBM constitutes a mixture of their representative polymer/sand their various chemical additives. The major polymer types are polyethylene, polypropylene,and polyvinyl chloride, with natural rubber and biodegradable polymers becoming increasingly more important. The most important additives are those that are biologically active, because to be effective such chemicals often have properties that make them resistant to photo-degradation and biodegradation. During their lifecycle,PBMs can be released into the environment form a variety of sources. The principal introduction routes being general littering, dumping of unwanted waste materials,migration from landfills and emission during refuse collection. Once in the environment,PBMs are primarily broken down by photo-degradation processes, but due to the complex chemical makeup of PBMs, receiving environments are potentially exposed to a mixture of macro-, meso-, and micro-size polymer fragments, leached additives, and subsequent degradation products. In environments where sunlight is absent (i.e., soils and the deep sea) degradation for most PBMs is minimal .The majority of literature to date that has addressed the environmental contamination or disposition of PBMs has focused on the marine environment. This is because the oceans are identified as the major sink for macro PBMs, where they are known to present a hazard to wildlife via entanglement and ingestion. The published literature has established the occurrence of microplastics in marine environment and beach sediments, but is inadequate as regards contamination of soils and freshwater sediments. The uptake of microplastics for a limited range of aquatic organisms has also been established, but there is a lack of information regarding soil organisms, and the long-term effects of microplastic uptake are also less well understood.There is currently a need to establish appropriate degradation test strategies consistent with realistic environmental conditions, because the complexity of environmental systems is lost when only one process (e.g., hydrolysis) is assessed in isolation. Enhanced methodologies are also needed to evaluate the impact of PBMs to soil and freshwater environments.

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.

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).

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).