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The aim of this study was to explore the relationship between pesticide contamination at 16 locations in 14 Dutch nature conservation areas and the abundance of Coleoptera (among which dung beetles) in excrements of grazing cattle. A wide spectrum of pesticides was measured in soil, vegetation and excrements of cattle, obtained from all locations. In the fresh dung pats sampled for chemical analysis, beetle numbers were counted and beetle species were identified. In total, 31 different pesticides (including some metabolites) were detected: 14 in fresh excrements, 17 in soil and 20 in vegetation. Total pesticide concentrations in soil, vegetation and excrements varied between 2.6 and 200 μg kg -1 dry matter. In vegetation, the most frequently encountered classes of pesticides (including some of their metabolites) were fungicides (9), herbicides (4) and insecticides (6). The total number of Coleoptera beetles in dung pats correlated negatively with the total concentration of insecticides in vegetation (Kendall's τ -0.501 at p < 0.05). The total concentrations of herbicides and fungicides were not statistically significant correlated with Coleoptera beetle numbers in the dung pats. Yet, the concentration of one single herbicide, viz. chlorpropham in vegetation correlated significantly negative with Coleoptera counts (Kendall's τ -0.603 at p < 0.01)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant concentrations. Toxicokinetic models are needed to facilitate extrapolation of bioaccumulation data across PFAS congeners and species. For the present study, we carried out an inventory of accumulation processes specific for PFAS, deviating from traditional Persistent Organic Pollutants (POPs). In addition, we reviewed toxicokinetic models on PFAS reported in literature, classifying them according to the number of compartments distinguished as a one-compartment model (1-CM), two-compartment model (2- CM) or a multi-compartment model, (multi-CM) as well as the accumulation processes included and the parameters used. As the inventory showed that simple 1-CMs were lacking, we developed a generic 1-CM of ourselves to include PFAS specific processes and validated the model for legacy perfluoroalkyl acids. Predicted summed elimination constants were accurate for long carbon chains (>C6), indicating that the model properly represented toxicokinetic processes for most congeners. Results for urinary elimination rate constants were mixed, which might be caused by the exclusion of reabsorption processes (renal reabsorption, enterohepatic circulation). The 1-CM needs to be improved further in order to better predict individual elimination pathways. Besides that, more data on PFAS-transporter specific processes are needed to extrapolate across PFAS congeners and species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Cornelia Welte reports financial support was provided by Nederlandse Organisatie voor Wetenschappelijk Onderzoek Utrecht. Mike Jetten reports financial support was provided by European Research Council. Mike Jetten reports financial support was provided by Nederlandse Organisatie voor Wetenschappelijk Onderzoek Utrecht., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Data from in vitro studies are routinely used to estimate in vivo hepatic clearance of chemicals and this information is needed to parameterise physiologically based kinetic models. Such clearance data can be obtained from laboratory experiments using liver microsomes, hepatocytes, precision-cut liver slices or recombinant enzymes. Irrespective of the selected test system, scaling factors are required to convert the in vitro measured intrinsic clearance to a whole liver intrinsic clearance. Scaling factors such as the hepatic microsomal protein per gram of liver and/or the amount of cytochrome P450 per hepatocyte provide a means to calculate the whole liver intrinsic clearance. Here, a database from the peer-reviewed literature has been developed and provides quantitative metrics on microsomal protein (MP) and cytochrome P450 contents in vertebrate orders namely amphibians, mammals, birds, fish and reptiles. This database allows to address allometric relationships between body weight and MP content, and body weight and cytochrome P450 content. A total of 85 and 74 vertebrate species were included to assess the relationships between log10 body weight versus log10 MP, and between log10 body weight and log10 cytochrome P450 content, respectively. The resulting slopes range from 0.76 to 1.45 in a range of vertebrate species. Such data-driven allometric relationships can be used to estimate the MP content necessary for in vitro to in vivo extrapolation of in vitro clearance data. Future work includes applications of these relationships for different vertebrate taxa using quantitative in vitro to in vivo extrapolation models coupled to physiologically based kinetic models using chemicals of relevance as case studies including pesticides, contaminants and feed additives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Petroleum refinery effluents (PRE) are wastewaters from industries associated with oil refining. Within Europe, PREs are regulated through local discharge permits and receive substantial treatment before emission. After treatment, PREs can still contain low levels of various pollutants potentially toxic to organisms. Earlier work, including whole-effluent toxicity assessments, has shown that the toxicity of permitted PREs is often limited. However, the extent to which PREs contribute to chemical pollution already present in the receiving environment is unknown. Therefore, our study aimed to assess the contribution of PREs to mixture toxic pressure in the environment, using the multi-substance potentially affected fraction of species (msPAF) as an indicator. Based on measured chemical concentrations, compiled species sensitivity distributions (SSD) and a mechanistic solubility model, msPAF levels were estimated for undiluted effluents at discharge points and diluted effluents downstream in receiving waters. Median msPAF-chronic and msPAF-acute levels of PREs at discharge points were 74% (P50) and 40% (P95), respectively. The calculated msPAF levels were reduced substantially to <5% downstream for most effluents (82%), indicating low to negligible toxicity of PREs in receiving environments beyond the initial mixing zone. Regardless of differences in endpoints and locations, hydrocarbons (mainly total petroleum hydrocarbons) and inorganics (mainly ammonia) explained at least 85% of the mixture toxic pressure. The msPAF levels of PREs were on average 2.5-4.5 orders of magnitude lower than msPAF levels derived from background pollution levels, suggesting that PREs were minor contributors to the toxic pressure in the environment. This study presents a generic methodology for quantifying the potential toxic pressure of PREs in the environment, identifying hotspots where more effective wastewater treatment could be needed. We explicitly discuss the uncertainties for further refinement and development of the method., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Markus Hjort and Yves Verhaegen works for Concawe, which represents the European fuel manufacturing industry, whose members operate the refinery sites included in the study. Concawe is a non-profit scientific organisation established in 1963 to conduct research on environmental issues relevant to the European fuel manufacturing industry. Concawe's operating principles aim to publish all research publicly, either on the Concawe website (https://www.concawe.eu) or as open access papers in scientific journals. Concawe has a long history of publications. Our mechanism to avoid bias is to publish our work, publish our data and methods so that the research community can reproduce and build on our findings. Mathijs G.D. Smit and Aaron D. Redman works for Shell and ExxonMobil, respectively, which are Concawe member companies. As this study was funded by Concawe these co-authors are bound to follow the mission and operating principles of Concawe. Jiaqi Wang, Tom M. Nolte, A. Jan Hendriks are employed by Radboud University and have received research funding from Concawe for conducting this study. Their research group independently carries out studies financed by university, governmental, commercial and other funding that is published in peer review journals., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nanotechnology brings benefits in fields such as biomedicine but nanoparticles (NPs) may also have adverse health effects. The effects of surface-modified NPs at the cellular level have major implications for both medicine and toxicology. Semi-empirical and mechanism-based models aid to understand the cellular transport of various NPs and its implications for quantitatively biological exposure while avoiding large-scale experiments. We hypothesized relationships between NPs-cellular elimination, surface functionality and elimination pathways by cells. Surface free energy components were used to characterize the transport of NPs onto membranes and with lipid vesicles, covering both influences by size and hydrophobicity of NPs. The model was built based on properties of neutral NPs and cells, defining Van de Waals forces, electrostatic forces and Lewis acid-base (polar) interactions between NPs and vesicles as well as between vesicles and cell membranes. We yielded a generic model for estimating exocytosis rate constants of various neutral NPs by cells based on the vesicle-transported exocytosis pathways. Our results indicate that most models are well fitted (R 2 ranging from 0.61 to 0.98) and may provide good predictions of exocytosis rate constants for NPs with differing surface functionalities (prediction errors are within 2 times for macrophages). Exocytosis rates differ between cancerous cells with metastatic potential and non-cancerous cells. Our model provides a reference for cellular elimination of NPs, and intends for medical applications and risk assessment., (© 2022. The Author(s).)

Preserving human and environmental health requires anthropogenic pollutants to be biologically degradable. Depending on concentration, both nutrients and pollutants induce and activate metabolic capacity in the endemic bacterial consortium, which in turn aids their degradation. Knowledge on such 'acclimation' is rarely implemented in risk assessment cost-effectively. As a result, an accurate description of the mechanisms and kinetics of biodegradation remains problematic. In this study, we defined a yield 'effectivity', comprising the effectiveness at which a pollutant (substrate) enhances its own degradation by inducing (biomass) cofactors involved therein. Our architecture for calculation represents the interplay between concentration and metabolism via both stoichiometric and thermodynamic concepts. The calculus for yield 'effectivity' is biochemically intuitive, implicitly embeds co-metabolism and distinguishes 'endogenic' from 'exogenic' substances' reflecting various phenomena in biodegradation and bio-transformation studies. We combined data on half-lives of pollutants/nutrients in wastewater and surface water with transition-state rate theory to obtain also experimental values for effective yields. These quantify the state of acclimation: the portion of biodegradation kinetics attributable to (contributed by) 'natural metabolism', in view of similarity to natural substances. Calculated and experimental values showed statistically significant correspondence. Particularly, carbohydrate metabolism and nucleic acid metabolism appeared relevant for acclimation (R 2  = 0.11-0.42), affecting rates up to 10 4.9(±0.7) times: under steady-state acclimation, a compound stoichiometrically identical to carbohydrates or nucleic acids, is 10 3.2 to 10 4.9 times faster aerobically degraded than a compound marginally similar. Our new method, simulating (contribution by) the state of acclimation, supplements existing structure-biodegradation and kinetic models for predicting biodegradation in wastewater and surface water. The accuracy of prediction may increase when characterizing nutrients/co-metabolites in terms of, e.g., elemental analysis. We discuss strengths and limitations of our approach by comparison to empirical and mechanism-based methods., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Neonicotinoids are currently the most widely used and sold insecticides in the world, providing effective pest control. Risk assessment of these and other pesticides by lab-based indicators is common. Yet, empirically and theoretically underpinning of extrapolation to indicators used in field surveys is severely limited. Consequently, the aim of our study was to quantify the toxicological and ecological impact of the neonicotinoids imidacloprid and thiacloprid to aquatic invertebrates. We derived Species Sensitivity Distributions (SSDs) based on chronic LC 50 data and Mean Species Abundance Relationships (MSARs), comparing these lab-based approaches to field data as well. MSARs are changes in mean species abundance (MSA) as a function of chemical exposure, providing insight into the overall decline of a community. The MSA expresses the mean abundance of species in disturbed conditions relative to their abundance in undisturbed habitat. The medians of the SSD of imidacloprid and thiacloprid for the different species were 16.45 μg/L and 26.40 μg/L, respectively. HC 50 s of the MSAR of imidacloprid and thiacloprid were 4.25 μg/L and 5.12 μg/L, respectively. The three taxonomic groups tested (insects, crustaceans and mollusks) did not differ significantly in sensitivity for imidacloprid and thiacloprid, both according to the SSDs and MSARs derived. Quantile exposure-response curves (99%-tile) were plotted showing the relative abundance (RA) of aquatic invertebrate species at increasing imidacloprid levels. The 99%-tile of the Relative Abundances (RA 99 ) of species and corresponding imidacloprid concentrations monitored in field surveys in the Netherlands was significantly lower than the Potentially Affected Fraction (PAF) calculated from the SSD. Yet, the MSA was similar to the RA 99 , suggesting that MSAR is an ecologically meaningful relationship for toxic stress estimated from lab data. Future efforts should be directed to additional empirical underpinning as well as determining the relationship of PAF to other metrics for ecosystem diversity and productivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

A toxicokinetic-toxicodynamic model was constructed to delineate the exposure-response causality. The model could be used: to predict metal accumulation considering the influence of water chemistry and biotic ligand characteristics; to simulate the dynamics of subcellular partitioning considering metabolism, detoxification, and elimination; and to predict chronic toxicity as represented by biomarker responses from the concentration of metals in the fraction of potentially toxic metal. The model was calibrated with data generated from an experiment in which the Zebra mussel Dreissena polymorpha was exposed to Cu at nominal concentrations of 25 and 50 μg/L and with varied Na + concentrations in water up to 4.0 mmol/L for 24 days. Data used in the calibration included physicochemical conditions of the exposure environment, Cu concentrations in subcellular fractions, and oxidative stress-induced responses, i.e. glutathione-S-transferase activity and lipid peroxidation. The model explained the dynamics of subcellular Cu partitioning and the effect mechanism reasonably well. With a low affinity constant for Na  +  binding to Cu 2+ uptake sites, Na  +  had limited influence on Cu 2+ uptake at low Na + concentrations in water. Copper was taken up into the metabolically available pool (MAP) at a largely higher rate than into the cellular debris. Similar Cu concentrations were found in these two fractions at low exposure levels, which could be attributed to sequestration pathways (metabolism, detoxification, and elimination) in the MAP. However, such sequestration was inefficient as shown by similar Cu concentrations in detoxified fractions with increasing exposure level accompanied by the increasing Cu concentration in the MAP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A toxicokinetic-toxicodynamic model based on subcellular metal partitioning is presented for simulating chronic toxicity of copper (Cu) from the estimated concentration in the fraction of potentially toxic metal (PTM). As such, the model allows for considering the significance of different pathways of metal sequestration in predicting metal toxicity. In the metabolically available pool (MAP), excess metals above the metabolic requirements and the detoxification and elimination capacity form the PTM fraction. The reversibly and irreversibly detoxified fractions were distinguished in the biologically detoxified compartment, while responses of organisms were related to Cu accumulation in the PTM fraction. The model was calibrated using the data on Cu concentrations in subcellular fractions and physiological responses measured by the glutathione S-transferase activity and the lipid peroxidation level during 24-day exposure of the Zebra mussel to Cu at concentrations of 25 and 50 µg/L and varying Na + concentrations up to 4.0 mmol/L. The model was capable of explaining dynamics in the subcellular Cu partitioning, e.g. the trade-off between elimination and detoxification as well as the dependence of net accumulation, elimination, detoxification, and metabolism on the exposure level. Increases in the net accumulation rate in the MAP contributed to increased concentrations of Cu in this fraction. Moreover, these results are indicative of ineffective detoxification at high exposure levels and spill-over effects of detoxification., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microplastic pollution is a growing, yet poorly understood problem. Here, we assessed the relationship between microplastic concentration and distance to rivers, shorelines, cities, sediment grain size or water depth in sediments of the world's largest (semi-)enclosed aquatic basins. Microplastic was extracted from sediment using density separation, elutriation and hydrophobic adhesion. Fibers and transparent or white microplastic particles were the most abundant shape and color. The microplastic concentration in sediments of the Black Sea was about twice as high compared to that in the Caspian Sea. Fragment concentrations decreased with depth, while fiber concentrations were independent of depth. Overall, no relationship with distance to shores, rivers and cities or with grain size was observed. However, within some depth classes concentrations were related to the distance from rivers, shores and cities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic toxicity of copper (Cu) at sublethal levels is associated with ionoregulatory disturbance and oxidative stress. These factors were considered in a toxicokinetic-toxicodynamic model in the present study. The ionoregulatory disturbance was evaluated by the activity of the Na + /K + -ATPase enzyme (NKA), while oxidative stress was presented by lipid peroxidation (LPO) and glutathione-S-transferase (GST) activity. NKA activity was related to the binding of Cu 2+ and Na  +  to NKA. LPO and GST activity were linked with the simulated concentration of unbound Cu. The model was calibrated using previously reported data and empirical data generated when zebra mussels were exposed to Cu. The model clearly demonstrated that Cu might inhibit NKA activity by reducing the number of functional pump sites and the limited Cu-bound NKA turnover rate. An ordinary differential equation was used to describe the relationship between the simulated concentration of unbound Cu and LPO/GST activity. Although this method could not explain the fluctuations in these biomarkers during the experiment, the measurements were within the confidence interval of estimations. Model simulation consistently shows non-significant differences in LPO and GST activity at two exposure levels, similar to the empirical observation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

It is well known that seagrass meadows sequester atmospheric carbon dioxide, protect coasts, provide nurseries for global fisheries, and enhance biodiversity. Large-scale restoration of lost seagrass meadows is urgently needed to revive these planetary ecosystem services, but sourcing donor material from natural meadows would further decline them. Therefore, we advocate the domestication and mariculture of seagrasses in order to produce the large quantities of seed needed for successful rewilding of the sea with seagrass meadows. We provide a roadmap for our proposed solution and show that 44% of seagrass species have promising reproductive traits for domestication and rewilding by seeds. The principle of partially domesticating species to enable subsequent large-scale rewilding may form a successful shortcut to restore threatened keystone species and their vital ecosystem services., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

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 (k b ) 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 k b 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 k b for some pharmaceuticals. Likely microbial activity was responsible instead of community composition. In the same inoculum, different k b values were measured, depending on initial concentration. In general, biodegradable compounds had a higher k b 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 k b 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., (© 2021. The Author(s).)

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 K ow ) 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.

Agricultural, industrial and household chemicals are emitted in large rivers along populated areas, transported by water and deposited in sediments, posing (eco)toxicological risks. Sediments have received less attention than surface waters, likely because of the intrinsic complexity of interactions between sediment constituents complicating correct framing of exposures. Sadly, thorough assessment of the in situ behavior of sediment constituents in bioassays is often not practical. Alternatively, we related physicochemical properties of sediments from field testing to results from bioassays. The case study covers Flemish sediment (incl. Scheldt and Meuse) and mortality of Hyalella azteca, a sensitive bio-indicator. Though variable across Flanders' main water bodies, heavy metals and ammoniacal nitrogen dominate the observed toxicity according to toxic unit (TU) assessments. Depending on the water body we explain between 50 and 90% of the variance in the observed H. azteca mortality, substantially more than previous ecotoxicity studies. We attribute the remaining variance to potential incoherently documented biophysicochemical sediment properties and concentrations of non-target biocides, testing conditions/set-ups and/or species variabilities. We discuss the relative influence of heavy metals/metaloxides, nitrogen (e.g. fertilizer), polycyclic aromatics and organochlorides. We highlight both direct and indirect mortality mechanisms. We note potential synergetic mixture effects between ammoniacal nitrogen and chromium. Such synergy may be phenomenological of 'standard' aerobic bioassays, and prove a complementary method alongside the 'acid-volatile sulfide test' to more effectively link concentration to toxicity. Future study ought to include variation in biophysicochemical properties between sampling locations and batch bioassays. Our approach enables water managers to interpret their monitoring data by converting sediment concentrations to H. azteca mortality and prioritize substances that contribute most., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As filter-feeders, freshwater mussels provide the ecosystem service (ES) of biofiltration. Chemical pollution may impinge on the provisioning of mussels' filtration services. However, few attempts have been made to estimate the impacts of chemical mixtures on mussels' filtration capacities in the field, nor to assess the economic benefits of mussel-provided filtration services for humans. The aim of the study was to derive and to apply a methodology for quantifying the economic benefits of mussel filtration services in relation to chemical mixture exposure. To this end, we first applied the bootstrapping approach to quantify the filtration capacity of dreissenid mussels when exposed to metal mixtures in the Rhine and Meuse Rivers in the Netherlands. Subsequently, we applied the value transfer method to quantify the economic benefits of mussel filtration services to surface water-dependent drinking water companies. The average mixture filtration inhibition (filtration rate reduction due to exposure to metal mixtures) to dreissenids was estimated to be <1% in the Rhine and Meuse Rivers based on the measured metal concentrations from 1999 to 2017. On average, dreissenids on groynes were estimated to filter the highest percentage of river discharge in the Nederrijn-Lek River (9.1%) and the lowest in the Waal River (0.1%). We estimated that dreissenid filtration services would save 110-12,000 euros/million m 3 for drinking water production when abstracting raw water at the end of respective rivers. Economic benefits increased over time due to metal emission reduction. This study presents a novel methodology for quantifying the economic benefits of mussel filtration services associated with chemical pollution, which is understandable to policymakers. The derived approach could potentially serve as a blueprint for developing methods in examining the economic value of other filter-feeders exposed to other chemicals and environmental stressors. We explicitly discuss the uncertainties for further development and application of the method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

The stenohaline zebra mussel, Dreissena polymorpha, is uniquely sensitive to the ionic composition of its aquatic environment. Waterborne copper (Cu) uptake and accumulation in zebra mussels were examined at various conditions in an environmentally relevant range in freshwater, i.e. Cu exposure levels (nominal concentrations of 25 and 50 μg/L), pH (5.8-8.3), and sodium (Na + ) concentrations (up to 4.0 mM). Copper accumulation was simulated by a kinetic model covering two compartments, the gills and the remaining tissues. The Cu uptake rate constant decreased with decreasing pH from 8.3 down to 6.5, indicating interactions between H + and Cu at uptake sites. The kinetic simulation showed dose-dependent effects of Na + on Cu uptake. At 25 μg/L Cu, addition of Na + at 0.5 mM significantly inhibited the Cu uptake rate, while no significant differences were found in the uptake rate upon further addition of Na + up to a concentration of 4.0 mM. At 50 μg/L Cu, the Cu uptake rate was not influenced by Na + addition. Calibration results exhibited dose-dependent elimination rates with more profound elimination with increasing exposure levels. With kinetic parameters calibrated at environmentally relevant conditions, in terms of pH and Na + concentrations, the model performed well in predicting Cu accumulation based on independent data sets. Estimates of the Cu concentration in mussels were within a factor of 2 of the measurements. This demonstrates potential application of kinetic models that are calibrated in environmentally relevant freshwater conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chemical pollution impinges on the quality of water systems and the ecosystem services (ESs) they provide. Expression of ESs in monetary units has become an essential tool for sustainable ecosystem management. However, the impact of chemical pollution on ESs is rarely quantified, and ES valuation often focuses on individual services without considering the total services provided by the ecosystem. The purpose of the study was to develop a stepwise approach to quantify the impact of sediment pollution on the total ES value provided by water systems. Thereby, we calculated the total ES value loss as a function of the multi-substance potentially affected fraction of species at the HC50 level (msPAF(HC50)). The function is a combination of relationships between, subsequently: the msPAF(HC50), diversity, productivity and total ES value. Regardless of the inherent differences between terrestrial and aquatic ecosystems, an increase of diversity generally corresponded to an increase in productivity with curvilinear or linear effects. A positive correlation between productivity and total values of ESs of biomes was observed. The combined relationships showed that 1% msPAF(HC50) corresponded to on average 0.5% (0.05-1.40%) of total ES value loss. The ES loss due to polluted sediments in the Waal-Meuse river estuary (the Netherlands) and Flemish waterways (Belgium) was estimated to be 0.3-5 and 0.6-10 thousand 2007$/ha/yr, respectively. Our study presents a novel methodology to assess the impact of chemical exposure on diversity, productivity, and total value that ecosystems provide. With sufficient monitoring data, our generic methodology can be applied for any chemical and region of interest and help water managers make informed decisions on cost-effective measures to remedy pollution. Acknowledging that the ES loss estimates as a function of PAF(HC50) are crude, we explicitly discuss the uncertainties in each step for further development and application of the methodology., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 HC 50 (the concentration at which 50% of the species is affected). The other two scenarios were based on the HC 5 and HC 95 . 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest Authors Tom Austin and Oliver Price are currently employed by RB, a manufacturer of products containing Ibuprofen and Ranitidine., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Distribution and elimination of petroleum products can be predicted in aerobic wastewater treatment plants (WWTPs) using models such as multimedia fate model SimpleTreat. An advantage of the SimpleTreat model is that it only requires a few basic properties of a chemical in wastewater to calculate partitioning, biodegradation and ultimately emissions to air, surface water and produced sludge. The SimpleTreat model structure reflects a WWTP scheme. However, refinery WWTPs typically incorporate more advanced treatment processes such as dissolved air flotation (DAF), a process that clarifies wastewaters by the removal of suspended matter such as oil or solids. The objective of this work was to develop a WWTP removal model that includes DAF treatment. To understand how including a DAF in the model affects the predicted concentrations of petroleum constituents in effluent, we replaced the primary sedimentation module in SimpleTreat with a module simulating DAF. Subsequently, we compared results from the WWTP-DAF model with results obtained with the original SimpleTreat model for a library of over 1500 representative hydrocarbon constituents. The increased air-water exchange in a WWTP-DAF unit resulted in higher predicted removal of volatile constituents. Predicted removal with DAF was on average 17% larger than removal with primary sedimentation. We compared modelled results with measured removal data from the literature, which supported that this model refinement continues to improve the technical basis of assessment of petroleum products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Both oxygen and temperature are fundamental factors determining metabolic performance, fitness, ecological niches, and responses of many aquatic organisms to climate change. Despite the importance of physical and physiological constraints on oxygen supply affecting aerobic metabolism of aquatic ectotherms, ecological theories such as the metabolic theory of ecology have focused on the effects of temperature rather than oxygen. This gap currently impedes mechanistic models from accurately predicting metabolic rates (i.e., oxygen consumption rates) of aquatic organisms and restricts predictions to resting metabolism, which is less affected by oxygen limitation. Here, we expand on models of metabolic scaling by accounting for the role of oxygen availability and temperature on both resting and active metabolic rates. Our model predicts that oxygen limitation is more likely to constrain metabolism in larger, warmer, and active fish. Consequently, active metabolic rates are less responsive to temperature than are resting metabolic rates, and metabolism scales to body size with a smaller exponent whenever temperatures or activity levels are higher. Results from a metaanalysis of fish metabolic rates are consistent with our model predictions. The observed interactive effects of temperature, oxygen availability, and body size predict that global warming will limit the aerobic scope of aquatic ectotherms and may place a greater metabolic burden on larger individuals, impairing their physiological performance in the future. Our model reconciles the metabolic theory with empirical observations of oxygen limitation and provides a formal, quantitative framework for predicting both resting and active metabolic rate and hence aerobic scope of aquatic ectotherms., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

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.

Chemical pollution of surface waters is considered an important driver for recent declines in biodiversity. Species sensitivity distributions (SSDs) are commonly used to evaluate the ecological risks of chemical exposure, accounting for variation in interspecies sensitivity. However, SSDs do not reflect the effects of chemical exposure on species abundance, considered an important endpoint in biological conservation. Although complex population modeling approaches lack practical applicability when it comes to the routine practice of lower tier chemical risk assessment, in the present study we show how information from widely available laboratory toxicity tests can be used to derive the change in mean species abundance (MSA) as a function of chemical exposure. These exposure-response MSA relationships combine insights into intraspecies exposure-response relationships and population growth theory. We showcase the practical applicability of our method for cadmium, copper, and zinc, and include a quantification of the associated statistical uncertainty. For all 3 metals, we found that concentrations hazardous for 5% of the species (HC 5 s) based on MSA relationships are systematically higher than SSD-based HC 5 values. Our proposed framework can be useful to derive abundance-based ecological protective criteria for chemical exposure, and creates the opportunity to assess abundance impacts of chemical exposure in the context of various other anthropogenic stressors. Environ Toxicol Chem 2020;39:2304-2313. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Chemistry describes transformation of matter with reaction equations and corresponding rate constants. However, accurate rate constants are not always easy to get. Here we focus on radical oxidation reactions. Analysis of over 500 published rate constants of hydroxyl radicals led us to hypothesize that a modified linear free-energy relationship (LFER) could be used to predict rate constants speedily, reliably and accurately. LFERs correlate the Gibbs activation-energy with the Gibbs energy of reaction. We calculated the latter as the sum of one-electron transfer and, if appropriate, proton transfer. We parametrized specific transition state effects to orbital delocalizability and the polarity of the reactant. The calculation time for 500 reactions is less than 8 hours on a standard desktop-PC. Rate constants were also calculated for hydrogen and methyl radicals; these controls show that the predictions are applicable to a broader set of oxidizing radicals. An accuracy of 30-40% (standard deviation) with reference to reported experimental values was found suitable for the screening of complex chemical systems for possibly relevant reactions. In particular, potentially relevant reactions can be singled out and scrutinized in detail when prioritizing chemicals for environmental risk assessment.

Recent declines of insects' biomass have been a major point of interest. While several causes, including use of neonicotinoids like imidacloprid, have been suggested, scientific underpinning is limited. The aim of our study was to assess the potential risk of imidacloprid for freshwater fauna in the Netherlands and to validate the SimpleBox model to allow application elsewhere. To this end, we compared imidacloprid concentrations estimated from emissions using the SimpleBox model to measurements obtained from monitoring databases and calculated the ecological risk based on measured concentrations for aquatic fauna. Imidacloprid concentration estimations were within the range measured, opening opportunities for application of SimpleBox to regions where measurements are limited. Aquatic insects were found to be most sensitive to imidacloprid while amphibians and fish are least sensitive to imidacloprid. In particular, the ecological risk of measured imidacloprid concentration in the Netherlands was 1%, implying that concentrations frequently exceed levels that are lethal in short-term experiments. Hence, based on lab toxicity data, the present study suggests that imidacloprid concentrations can be high enough to explain insect decline observed in the same areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Persistent organic pollutants (POPs) are of great concern for decades due to their persistence, bioaccumulation and long-range transport potential. Multimedia fate models are useful scientific and decision-support tools for predicting the chemical fate in the environment. The SimpleBox multimedia fate model (v4.0) was used in this study to estimate the impact of POP emissions from the European and North American mainland on POP contamination in the Arctic. The purpose of the study was to evaluate the performance of SimpleBox by comparing estimations to measurements. Model performance for the air compartment was reasonable as estimated concentrations were generally within a factor of five of measured concentrations. SimpleBox suggested higher POP concentrations in Arctic oceans than in temperate oceans, contrary to the few measured data. Discrepancies between estimations and measurements may be attributed to the variability in emission estimates and degradation rates of POPs, representativeness of monitoring data, and a missing snow and ice environmental compartment in SimpleBox. Emission rates and degradation rate constants were the most influential input parameters in SimpleBox based on sensitivity analysis. Suggestions for improvements of SimpleBox refining POP risk assessment are provided., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Packaging materials can be a source of chemical contaminants in food. Process-based migration models (PMM) predict the chemical fraction transferred from packaging materials to food (F C ) for application in prioritisation tools for human exposure. These models, however, have a relatively limited applicability domain and their predictive performance is typically low. To overcome these limitations, we developed a linear mixed-effects model (LMM) to statistically relate measured F C to properties of chemicals, food, packaging, and experimental conditions. We found a negative relationship between the molecular weight (MW) and F C , and a positive relationship with the fat content of the food depending on the octanol-water partitioning coefficient of the migrant. We also showed that large chemicals (MW > 400 g/mol) have a higher migration potential in packaging with low crystallinity compared with high crystallinity. The predictive performance of the LMM for chemicals not included in the database in contact with untested food items but known packaging material was higher (Coefficient of Efficiency (CoE) = 0.21) compared with a recently developed PMM (CoE = -5.24). We conclude that our empirical model is useful to predict chemical migration from packaging to food and prioritise chemicals in the absence of measurements.

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 R 2 training =0.69 (training set of 51 compounds) and R 2 validation =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 R 2 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Xenobiotics from anthropogenic and natural origin enter animal feed and human food as regulated compounds, environmental contaminants or as part of components of the diet. After dietary exposure, a chemical is absorbed and distributed systematically to a range of organs and tissues, metabolised, and excreted. Physiologically based kinetic (PBK) models have been developed to estimate internal concentrations from external doses. In this study, a generic multi-compartment PBK model was developed for chicken. The PBK model was implemented for seven compounds (with log K ow range -1.37-6.2) to quantitatively link external dose and internal dose for risk assessment of chemicals. Global sensitivity analysis was performed for a hydrophilic and a lipophilic compound to identify the most sensitive parameters in the PBK model. Model predictions were compared to measured data according to dataset-specific exposure scenarios. Globally, 71% of the model predictions were within a 3-fold change of the measured data for chicken and only 7% of the PBK predictions were outside a 10-fold change. While most model input parameters still rely on in vivo experiments, in vitro data were also used as model input to predict internal concentration of the coccidiostat monensin. Future developments of generic PBK models in chicken and other species of relevance to animal health risk assessment are discussed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the European Food Safety Authority (EFSA) [Contract number: EFSA/SCER/2014/06]., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mechanistic models based on chemical properties of metals and body size have received substantial attention for their potential application to various metals and to different conditions without required calibration. This advantage has been demonstrated for a number of metals, such as Cd and Ag. However, the capacity of metal-specific chemical properties to explain variations in the accumulation for platinum-group elements (PGEs) has not been investigated yet, although emission of these metals is of increasing concern. Once being released, PGEs exist in the environment in mixtures with other metals. The present study attempted to model the accumulation of Pd and Pt in mixtures with Ag and Cd in the zebra mussel (Dreissena polymorpha) from the aqueous phase; and to investigate the potential application of mechanistic models to Pd and Pt. The present study showed statistically insignificant differences in metal accumulation among size groups in a narrow range of shell length (16-22 mm). Kinetic models could simulate well the accumulation of Cd, Ag, and Pt when metal-specific responses of zebra mussels are taken into consideration. These responses include enhanced immobilisation as a detoxifying mechanism and exchange between soft tissues and shells via the extrapallial fluid. Environmental conditions, e.g. the presence of abiotic ligands such as chloride, might also play an important role in metal accumulation. Significant relationships between the absorption efficiency and the covalent index indicate the potential application of mechanistic models based on this chemical property to Pt., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

The development of three generic multi-compartment physiologically based kinetic (PBK) models is described for farm animal species, i.e. cattle, sheep, and swine. The PBK models allow one to quantitatively link external dose and internal dose for risk assessment of chemicals relevant to food and feed safety. Model performance is illustrated by predicting tissue concentrations of melamine and oxytetracycline and validated through comparison with measured data. Overall, model predictions were reliable with 71% of predictions within a 3-fold of the measured data for all three species and only 6% of predictions were outside a 10-fold of the measured data. Predictions within a 3-fold change were best for cattle, followed by sheep, and swine (82%, 76%, and 63%). Global sensitivity analysis was performed to identify the most sensitive parameters in the PBK model. The sensitivity analysis showed that body weight and cardiac output were the most sensitive parameters. Since interspecies differences in metabolism impact on the fate of a wide range of chemicals, a key step forward is the introduction of species-specific information on transporters and metabolism including expression and activities., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of down-the-drain products and the resultant release of chemicals may lead to pressures on the freshwater environment. Ecotoxicological impact assessment is a commonly used approach to assess chemical products but is still influenced by several uncertainty and variability sources. As a result, the robustness and reliability of such assessments can be questioned. A comprehensive and systematic assessment of these sources is, therefore, needed to increase their utility and credibility. In this study, we present a method to systematically analyse the uncertainty and variability of the potential ecotoxicological impact (PEI) of chemicals using a portfolio of 54 shampoo products. We separately quantified the influence of the statistical uncertainty in the prediction of physicochemical properties and freshwater toxicity as predicted from Quantitative Structure-Property Relationships (QSPRs) and Quantitative Structure-Activity Relationships (QSARs) respectively, and of various sources of spatial and technological variability as well as variability in consumer habits via 2D Monte Carlo simulations. Overall, the variation in the PEIs of shampoo use was mainly the result of uncertainty due to the use of toxicity data from three species only. All uncertainty sources combined resulted in PEIs ranging on average over seven orders of magnitude (ratio of the 90th to the 10th percentile) so that an absolute quantification of the ecological risk would not be meaningful. In comparison, variation in shampoo composition was the most influential source of variability, although less than compared to uncertainty, leading to PEIs ranging over three orders of magnitude. Increasing the number of toxicity data by increasing the number of species, either through additional measurements or ecotoxicological modelling (e.g. using Interspecies Correlation Equations), should get priority to improve the reliability of PEIs. These conclusions are not limited to shampoos but are applicable more generally to the down-the-drain products since they all have similar data limitations and associated uncertainties relating to the availability of ecotoxicity data and variability in consumer habits and use., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Simultaneous presence of metals and parasites in fish might lead to potential risks to human health. Parasites might influence metal accumulation and disturb detoxification in fish, thereby affecting biomarkers of fish responses as well as metal biomagnification in humans. It is, therefore, of importance to take into account parasite infection when investigating metal accumulation in fish. However, mechanisms of metal accumulation and distribution in fish-parasite systems are not integrated into current approaches. The present study proposes a new physiologically based pharmacokinetic model for mechanistic simulation of metal partitioning between intestinal parasites and their hosts. As a particular case, Ag accumulation in the system of chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis was investigated. As a novelty, fish cardiac output and organ-specific blood flow distribution were incorporated in our model. This approach distinguishes the current model from the ones developed previously. It also facilitates model extrapolation and application to varying conditions. In general, the model explained Ag accumulation in the system well, especially in chub gill, storage (including skin, muscle, and carcass), and liver. The highest concentration of Ag was found in the liver. The accumulation of Ag in the storage, liver, and gill compartments followed a similar pattern, i.e., increasing during the exposure and decreasing during the depuration. The model also generated this observed trend. However, the model had a weaker performance for simulating Ag accumulation in the intestine and the kidney. Silver accumulation in these organs was less evident with considerable variations.

Background: In research in residential care, health-related quality of life (HRQL) is usually measured using either observational methods or standardized questionnaires. DEMQOL-Proxy is a standardized questionnaire measuring HRQL of people with dementia and is usually reported by a family carer. However, not all residents have a family carer who visits often enough to act as a proxy., Objectives: We evaluated the psychometric performance of DEMQOL-Proxy when reported on behalf of people with dementia in residential care by a "trained proxy" (DEMQOL-Proxy-TP)., Participants: We recruited a sample of 87 people with dementia living in care homes around the UK., Methods: We used modern psychometric methods (based on the Rasch model) to evaluate DEMQOL-Proxy-TP (on behalf of 85 residents) in a cross-sectional study. We evaluated scale-to-sample targeting, ordering of item thresholds, item fit to the model and differential item functioning (sex, age, type of dementia), local independence, unidimensionality and reliability on the full set of items (31 items) and also a smaller item set (26 items)., Results: The smaller item set (DEMQOL-Proxy-TP-26) performed better than the original item set and was found to fit the model ( p = 0.68). Nevertheless, 17 items were found to have disordered thresholds, and 24 pairs of items showed local dependency (residual correlations >0.3). There were also some areas where scale-to-sample targeting could be improved., Conclusion: After resolving the identified anomalies, DEMQOL-Proxy-TP can provide adequate measurement of HRQL of people with dementia living in residential care, particularly when no family carer is available. This can be interpreted at the group level but is not yet robust enough for use at the individual level. Future work will compare these results with the psychometric performance of DEMQOL-Proxy reported by family carers and DEMQOL self-reported by the residents., Competing Interests: Disclosure Dr Smith is one of the original developers of DEMQOL and DEMQOL-Proxy. The other authors report no other conflicts of interest in this work.

Ecological risks (ERs) of pollutants are typically assessed using species sensitivity distributions (SSDs), based on effect concentrations obtained from bioassays with unknown representativeness for field conditions. Alternatively, monitoring data relating breeding success in bird populations to egg concentrations may be used. In this study, we developed a procedure to derive SSDs for birds based on field data of egg concentrations and reproductive success. As an example, we derived field-based SSDs for p, p'-DDE and polychlorinated biphenyls (PCBs) exposure to birds. These SSDs were used to calculate ERs for these two chemicals in the American Great Lakes and the Arctic. First, we obtained field data of p, p'-DDE and PCBs egg concentrations and reproductive success from the literature. Second, these field data were used to fit exposure-response curves along the upper boundary (right margin) of the response's distribution (95th quantile), also called quantile regression analysis. The upper boundary is used to account for heterogeneity in reproductive success induced by other external factors. Third, the species-specific EC 10/50 s obtained from the field-based exposure-response curves were used to derive SSDs per chemical. Finally, the SSDs were combined with specific exposure data for both compounds in the two areas to calculate the ER. We found that the ERs of combined exposure to these two chemicals were a factor of 5-35 higher in the Great Lakes compared to Arctic regions. Uncertainty in the species-specific exposure-response curves and related SSDs was mainly caused by the limited number of field exposure-response data for bird species. With sufficient monitoring data, our method can be used to quantify field-based ecological risks for other chemicals, species groups, and regions of interest.

Deriving reliable estimates of chemical emissions to the environment is a key challenge for impact and risk assessment methods and typically the associated uncertainty is not characterised. We have developed an approach to spatially quantify annual chemical emission loads to the aquatic environment together with their associated uncertainty using consumer survey data and publicly accessible and non-confidential data sources. The approach is applicable for chemicals widely used across a product sector. Product usage data from consumer survey studies in France, the Netherlands, South Korea and the USA were combined with information on typical product formulations, wastewater removal rates, and the spatial distribution of populations and wastewater treatment plants (WWTPs) in the four countries. Results are presented for three chemicals common to three types of personal care products (shampoo, conditioner, and bodywash) at WWTP and national levels. Uncertainty in WWTP-specific emission estimates was characterised with a 95% confidence interval and ranged up to a factor of 4.8 around the mean, mainly due to uncertainty associated with removal efficiency. Estimates of whole country product usage were comparable to total market estimates derived from sectorial market sales data with differences ranging from a factor 0.8 (for the Netherlands) to 5 (for the USA). The proposed approach is suitable where measured data on chemical emissions is missing and is applicable for use in risk assessments and chemical footprinting methods when applied to specific product categories., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Microbial biomass and acclimation can affect the removal of organic chemicals in natural surface waters. In order to account for these effects and develop more robust models for biodegradation, we have compiled and curated removal data for un-acclimated (pristine) surface waters on which we developed quantitative structure-activity relationships (QSARs). Global analysis of the very heterogeneous dataset including neutral, anionic, cationic and zwitterionic chemicals (N = 233) using a random forest algorithm showed that useful predictions were possible (Q ext 2 = 0.4-0.5) though relatively large standard errors were associated (SDEP ∼0.7). Classification of the chemicals based on speciation state and metabolic pathway showed that biodegradation is influenced by the two, and that the dependence of biodegradation on chemical characteristics is non-linear. Class-specific QSAR analysis indicated that shape and charge distribution determine the biodegradation of neutral chemicals (R 2 ∼ 0.6), e.g. through membrane permeation or binding to P450 enzymes, whereas the average biodegradation of charged chemicals is 1 to 2 orders of magnitude lower, for which degradation depends more directly on cellular uptake (R 2 ∼ 0.6). Further analysis showed that specific chemical classes such as peptides and organic halogens are relatively less biodegradable in pristine surface waters, resulting in the need for the microbial consortia to acclimate. Additional literature data was used to verify an acclimation model (based on Monod-type kinetics) capable of extrapolating QSAR predictions to acclimating conditions such as in water treatment, downstream lakes and large rivers under μg L -1 to mg L -1 concentrations. The framework developed, despite being based on multiple assumptions, is promising and needs further validation using experimentation with more standardised and homogenised conditions as well as adequate characterization of the inoculum used.

After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R 2  = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

There is a need to study the time course of toxic chemical effects on organisms because there might be a time lag between the onset of chemical exposure and the corresponding adverse effects. For aquatic organisms, crude oil and oil constituents originating from either natural seeps or human activities can be relevant case studies. In the present study the authors tested a generic toxicokinetic model to quantify the time-varying effects of various oil constituents on the survival of aquatic organisms. The model is based on key parameters applicable to an array of species and compounds with baseline toxicity reflected by a generic, internal toxicity threshold or critical body burden (CBB). They compared model estimates with experimental data on the effects of 8 aromatic oil constituents on the survival of aquatic species including crustaceans and fish. The average model uncertainty, expressed as the root mean square error, was 0.25 (minimum-maximum, 0.04-0.67) on a scale between 0 and 1. The estimated survival was generally lower than the measured survival right after the onset of oil constituent exposure. In contrast, the model underestimated the maximum mortality for crustaceans and fish observed in the laboratory. Thus, the model based on the CBB concept failed to adequately predict the lethal effects of the oil constituents on crustaceans and fish. Possible explanations for the deviations between model estimates and observations may include incorrect assumptions regarding a constant lethal body burden, the absence of biotransformation products, and the steady state of aromatic hydrocarbon concentrations in organisms. Clearly, a more complex model approach than the generic model used in the present study is needed to predict toxicity dynamics of narcotic chemicals. Environ Toxicol Chem 2017;36:128-136. © 2016 SETAC., (© 2016 SETAC.)

Marine plastic debris are found worldwide in oceans and coastal areas. They degrade only slowly and contain chemicals added during manufacture or absorbed from the seawater. Therefore, they can pose a long-lasting contaminant source and potentially transfer chemicals to marine organisms when ingested. In order to assess their risk, the contaminant concentration in the plastics needs to be estimated and differences understood. We collected from literature plastic water partition coefficients of various organic chemicals for seven plastic types: polydimethylsiloxane (PDMS), high-density, low-density and ultra-high molecular weight polyethylene (LDPE, HDPE, UHMWPE), polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC). Most data was available for PDMS (1060) and LDPE (220), but much less for the remaining plastics (73). Where possible, regression models were developed and the partitioning was compared between the different plastic types. The partitioning of chemicals follows the order of LDPE≈HDPE≥PP>PVC≈PS. Data describing the impact of weathering are urgently needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)