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Substituted para-benzoquinones and hydroquinones are ubiquitous transformation products that arise during oxidative water treatment of phenolic precursors, for example through ozonation or chlorination. The benzoquinone structural motive is associated with mutagenicity and carcinogenicity, and also with induction of the oxidative stress response through the Nrf2 pathway. For either endpoint, toxicological data for differently substituted compounds are scarce. In this study, an oxidative stress response, as indicated by the AREc32 in vitro bioassay, was induced by differently substituted para-benzoquinones, but also by the corresponding hydroquinones. Bioassays that indicate defense against genotoxicity (p53RE-bla) and DNA repair activity (UmuC) were not activated by these compounds. Stability tests conducted under incubation conditions, but in the absence of cell lines, showed that tested para-benzoquinones reacted rapidly with constituents of the incubation medium. Compounds were abated already in phosphate buffer, but even faster in biological media, with reactions attributed to amino- and thiol-groups of peptides, proteins, and free amino acids. The products of these reactions were often the corresponding substituted hydroquinones. Conversely, differently substituted hydroquinones were quantitatively oxidized to p-benzoquinones over the course of the incubation. The observed induction of the oxidative stress response was attributed to hydroquinones that are presumably oxidized to benzoquinones inside the cells. Despite the instability of the test compounds in the incubation medium, the AREc32 in vitro bioassay could be used as an unspecific sum parameter to detect para-benzoquinones and hydroquinones in oxidatively treated waters.
Peter R. Tentscher; Beate I. Escher; Rita Schlichting; Maria König; Nadine Bramaz; Kristin Schirmer; Urs von Gunten. Toxic effects of substituted p-benzoquinones and hydroquinones in in vitro bioassays are altered by reactions with the cell assay medium. Water Research 2021, 202, 117415 .
AMA StylePeter R. Tentscher, Beate I. Escher, Rita Schlichting, Maria König, Nadine Bramaz, Kristin Schirmer, Urs von Gunten. Toxic effects of substituted p-benzoquinones and hydroquinones in in vitro bioassays are altered by reactions with the cell assay medium. Water Research. 2021; 202 ():117415.
Chicago/Turabian StylePeter R. Tentscher; Beate I. Escher; Rita Schlichting; Maria König; Nadine Bramaz; Kristin Schirmer; Urs von Gunten. 2021. "Toxic effects of substituted p-benzoquinones and hydroquinones in in vitro bioassays are altered by reactions with the cell assay medium." Water Research 202, no. : 117415.
Equilibrium passive sampling employing polydimethylsiloxane (PDMS) as a sampling phase can be used for the extraction of complex mixtures of organic chemicals from lipid-rich biota. We extended the method to lean tissues and more hydrophilic chemicals by implementing a mass-balance model for partitioning between lipids, proteins, and water in tissues and by accelerating uptake kinetics with a custom-built stirrer that effectively decreased time to equilibrium to less than 8 days even for a homogenized liver tissue with an only 4% lipid content. The partition constants log Klipid/PDMS between tissues and PDMS were derived from measured concentration in PDMS and the mass-balance model and were very similar for 40 neutral chemicals with octanol–water partition constants 1.4 < log Kow < 8.7, that is, log Klipid/PDMS of 1.26 (95% CI, 1.13–1.39) for the adipose tissue, 1.16 (1.00–1.33) for the liver, and 0.58 (0.42–0.73) for the brain. This conversion factor can be applied to interpret chemical analysis and in vitro bioassays after additionally accounting for a small fraction of coextracted lipids of <0.7% of the PDMS weight. PDMS is more widely applicable for passive sampling of mammalian tissues than previously thought, both, in terms of diversity of chemicals and the range of lipid contents of tissues and, therefore, an ideal method for human biomonitoring to be combined with in vitro bioassays.
Andreas Baumer; Sandra Jäsch; Nadin Ulrich; Ingo Bechmann; Julia Landmann; Beate I. Escher. Kinetics of Equilibrium Passive Sampling of Organic Chemicals with Polymers in Diverse Mammalian Tissues. Environmental Science & Technology 2021, 1 .
AMA StyleAndreas Baumer, Sandra Jäsch, Nadin Ulrich, Ingo Bechmann, Julia Landmann, Beate I. Escher. Kinetics of Equilibrium Passive Sampling of Organic Chemicals with Polymers in Diverse Mammalian Tissues. Environmental Science & Technology. 2021; ():1.
Chicago/Turabian StyleAndreas Baumer; Sandra Jäsch; Nadin Ulrich; Ingo Bechmann; Julia Landmann; Beate I. Escher. 2021. "Kinetics of Equilibrium Passive Sampling of Organic Chemicals with Polymers in Diverse Mammalian Tissues." Environmental Science & Technology , no. : 1.
Seven treatment wetlands and a municipal wastewater treatment plant (WWTP) were weekly monitored over the course of one year for removal of conventional wastewater parameters, selected micropollutants (caffeine, ibuprofen, naproxen, benzotriazole, diclofenac, acesulfame, and carbamazepine) and biological effects. The treatment wetland designs investigated include a horizontal subsurface flow (HF) wetland and a variety of wetlands with intensification (aeration, two-stages, or reciprocating flow). Complementary to the common approach of analyzing individual chemicals, in vitro bioassays can detect the toxicity of a mixture of known and unknown components given in a water sample. A panel of five in vitro cell-based reporter gene bioassays was selected to cover environmentally relevant endpoints (AhR: indicative of activation of the aryl hydrocarbon receptor; PPARγ: binding to the peroxisome proliferator-activated receptor gamma; ERα: activation of the estrogen receptor alpha; GR: activation of the glucocorticoid receptor; oxidative stress response). While carbamazepine was persistent in the intensified treatment wetlands, mean monthly mass removal of up to 51% was achieved in the HF wetland. The two-stage wetland system showed highest removal efficacy for all biological effects (91% to >99%). The removal efficacy for biological effects ranged from 56% to 77% for the HF wetland and 60% to 99% for the WWTP. Bioanalytical equivalent concentrations (BEQs) for AhR, PPARγ, and oxidative stress response were often below the recommended effect-based trigger (EBT) values for surface water, indicating the great benefit for using nature-based solutions for water treatment. Intensified treatment wetlands remove both individual micropollutants and mixture effects more efficiently than conventional (non-aerated) HF wetlands, and in some cases, the WWTP.
Nadine A. Sossalla; Jaime Nivala; Thorsten Reemtsma; Rita Schlichting; Maria König; Nicolas Forquet; Manfred van Afferden; Roland A. Müller; Beate I. Escher. Removal of micropollutants and biological effects by conventional and intensified constructed wetlands treating municipal wastewater. Water Research 2021, 201, 117349 .
AMA StyleNadine A. Sossalla, Jaime Nivala, Thorsten Reemtsma, Rita Schlichting, Maria König, Nicolas Forquet, Manfred van Afferden, Roland A. Müller, Beate I. Escher. Removal of micropollutants and biological effects by conventional and intensified constructed wetlands treating municipal wastewater. Water Research. 2021; 201 ():117349.
Chicago/Turabian StyleNadine A. Sossalla; Jaime Nivala; Thorsten Reemtsma; Rita Schlichting; Maria König; Nicolas Forquet; Manfred van Afferden; Roland A. Müller; Beate I. Escher. 2021. "Removal of micropollutants and biological effects by conventional and intensified constructed wetlands treating municipal wastewater." Water Research 201, no. : 117349.
Despite elaborate regulation of agricultural pesticides, their occurrence in non-target areas has been linked to adverse ecological effects on insects in several field investigations. Their quantitative role in contributing to the biodiversity crisis is, however, still not known. In a large-scale study across 101 sites of small lowland streams in Central Europe we revealed that 83% of agricultural streams did not meet the pesticide-related ecological targets. For the first time we identified that agricultural nonpoint-source pesticide pollution was the major driver in reducing vulnerable insects in aquatic invertebrate communities, exceeding the relevance of other anthropogenic stressors such as poor hydro-morphological structure. We revealed that the current authorisation of pesticides, which aims to prevent adverse effects, underestimates the actual ecological risk as (i) measured pesticide concentrations exceeded current regulatory threshold levels in 81% of the agricultural streams investigated, (ii) for several pesticides the inertia of the authorisation process impedes the incorporation of new scientific knowledge and (iii) existing thresholds of invertebrate toxicity drivers are not protective by a factor of 5.3 to 40. To provide more reliable thresholds, the authorization process needs to include monitoring-derived information on pesticide effects at the ecosystem level. Here, we derive thresholds that ensure a protection of the invertebrate stream community.
Matthias Liess; Liana Liebmann; Philipp Vormeier; Oliver Weisner; Rolf Altenburger; Dietrich Borchardt; Werner Brack; Antonis Chatzinotas; Beate Escher; Kaarina Foit; Roman Gunold; Sebastian Henz; Kristina L. Hitzfeld; Mechthild Schmitt-Jansen; Norbert Kamjunke; Oliver Kaske; Saskia Knillmann; Martin Krauss; Eberhard Küster; Moritz Link; Maren Lück; Monika Möder; Alexandra Müller; Albrecht Paschke; Ralf B. Schäfer; Anke Schneeweiss; Verena C. Schreiner; Tobias Schulze; Gerrit Schüürmann; Wolf von Tümpling; Markus Weitere; Jörn Wogram; Thorsten Reemtsma. Pesticides are the dominant stressors for vulnerable insects in lowland streams. Water Research 2021, 201, 117262 .
AMA StyleMatthias Liess, Liana Liebmann, Philipp Vormeier, Oliver Weisner, Rolf Altenburger, Dietrich Borchardt, Werner Brack, Antonis Chatzinotas, Beate Escher, Kaarina Foit, Roman Gunold, Sebastian Henz, Kristina L. Hitzfeld, Mechthild Schmitt-Jansen, Norbert Kamjunke, Oliver Kaske, Saskia Knillmann, Martin Krauss, Eberhard Küster, Moritz Link, Maren Lück, Monika Möder, Alexandra Müller, Albrecht Paschke, Ralf B. Schäfer, Anke Schneeweiss, Verena C. Schreiner, Tobias Schulze, Gerrit Schüürmann, Wolf von Tümpling, Markus Weitere, Jörn Wogram, Thorsten Reemtsma. Pesticides are the dominant stressors for vulnerable insects in lowland streams. Water Research. 2021; 201 ():117262.
Chicago/Turabian StyleMatthias Liess; Liana Liebmann; Philipp Vormeier; Oliver Weisner; Rolf Altenburger; Dietrich Borchardt; Werner Brack; Antonis Chatzinotas; Beate Escher; Kaarina Foit; Roman Gunold; Sebastian Henz; Kristina L. Hitzfeld; Mechthild Schmitt-Jansen; Norbert Kamjunke; Oliver Kaske; Saskia Knillmann; Martin Krauss; Eberhard Küster; Moritz Link; Maren Lück; Monika Möder; Alexandra Müller; Albrecht Paschke; Ralf B. Schäfer; Anke Schneeweiss; Verena C. Schreiner; Tobias Schulze; Gerrit Schüürmann; Wolf von Tümpling; Markus Weitere; Jörn Wogram; Thorsten Reemtsma. 2021. "Pesticides are the dominant stressors for vulnerable insects in lowland streams." Water Research 201, no. : 117262.
Discussions are ongoing on which dose metric should be used for quantitative in vitro-to-in vivo extrapolation (QIVIVE) of in vitro bioassay data. The nominal concentration of the test chemicals is most commonly used and easily accessible, while the concentration freely dissolved in the assay medium is considered to better reflect the bioavailable concentration but is tedious to measure. The aim of this study was to elucidate how much QIVIVE results will differ when using either nominal or freely dissolved concentrations. QIVIVEnom and QIVIVEfree ratios, that is, the ratios of plasma concentrations divided by in vitro effect concentrations, were calculated for 10 pharmaceuticals using previously published nominal and freely dissolved effect concentrations for the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) and the activation of oxidative stress response. The QIVIVEnom ratios were higher than QIVIVEfree ratios by up to a factor of 60. The risk of in vivo effects was classified as being high or low for four chemicals using the QIVIVEnom and for three chemicals using QIVIVEfree ratios. Unambiguous classification was possible for nine chemicals by combining the QIVIVEnom or QIVIVEfree ratios with the respective specificity ratios (SRnom or SRfree) of the in vitro effect data, which helps to identify whether the specific effect was influenced by cytotoxicity. QIVIVEfree models should be preferred as they account for differences in bioavailability between in vitro and in vivo, but QIVIVEnom may still be useful for screening the effects of large numbers of chemicals because it is generally more conservative. The use of SR of the in vitro effect data as a second classification factor is recommended for QIVIVEnom and QIVIVEfree models because a clearer picture can be obtained with respect to the likelihood that a biological effect will occur and that it is not caused by nonspecific cytotoxicity.
Luise Henneberger; Julia Huchthausen; Niklas Wojtysiak; Beate I. Escher. Quantitative In Vitro-to-In Vivo Extrapolation: Nominal versus Freely Dissolved Concentration. Chemical Research in Toxicology 2021, 34, 1175 -1182.
AMA StyleLuise Henneberger, Julia Huchthausen, Niklas Wojtysiak, Beate I. Escher. Quantitative In Vitro-to-In Vivo Extrapolation: Nominal versus Freely Dissolved Concentration. Chemical Research in Toxicology. 2021; 34 (4):1175-1182.
Chicago/Turabian StyleLuise Henneberger; Julia Huchthausen; Niklas Wojtysiak; Beate I. Escher. 2021. "Quantitative In Vitro-to-In Vivo Extrapolation: Nominal versus Freely Dissolved Concentration." Chemical Research in Toxicology 34, no. 4: 1175-1182.
Suspended particulate matter (SPM) plays an important role in the fate of organic micropollutants in rivers during rain events, when sediments are remobilized and turbid runoff components enter the rivers. Under baseflow conditions, the SPM concentration is low and the contribution of SPM-bound contaminants to the overall risk of organic contaminants in rivers is assumed to be negligible. To challenge this assumption, we explored if SPM may act as a source or sink for all or specific groups of organic chemicals in a small river. The concentrations of over 600 contaminants and the mixture effects stemming from all chemicals in in vitro bioassays were measured for river water, SPM, and the surface sediment after solid-phase extraction or exhaustive solvent extraction. The bioavailable fractions of chemicals and mixture effects were estimated after passive equilibrium sampling of enriched SPM slurries and sediments in the lab. Dissolved compounds dominated the total chemical burden in the water column (water plus SPM) of the river, whereas SPM-bound chemicals contributed up to 46% of the effect burden even if the SPM concentration in rivers was merely 1 mg/L. The equilibrium between water and SPM was still not reached under low-flow conditions with SPM as a source of water contamination. The ratios of SPM-associated to sediment-associated neutral and hydrophobic chemicals as well as the ratios of the mixture effects expressed as bioanalytical equivalent concentrations were close to 1, suggesting that the surface sediment can be used as a proxy for SPM under baseflow conditions when the sampling of a large amount of water to obtain sufficient SPM cannot be realized.
Lili Niu; Jörg Ahlheim; Clarissa Glaser; Roman Gunold; Luise Henneberger; Maria König; Martin Krauss; Marc Schwientek; Christiane Zarfl; Beate I. Escher. Suspended Particulate Matter—A Source or Sink for Chemical Mixtures of Organic Micropollutants in a Small River under Baseflow Conditions? Environmental Science & Technology 2021, 55, 5106 -5116.
AMA StyleLili Niu, Jörg Ahlheim, Clarissa Glaser, Roman Gunold, Luise Henneberger, Maria König, Martin Krauss, Marc Schwientek, Christiane Zarfl, Beate I. Escher. Suspended Particulate Matter—A Source or Sink for Chemical Mixtures of Organic Micropollutants in a Small River under Baseflow Conditions? Environmental Science & Technology. 2021; 55 (8):5106-5116.
Chicago/Turabian StyleLili Niu; Jörg Ahlheim; Clarissa Glaser; Roman Gunold; Luise Henneberger; Maria König; Martin Krauss; Marc Schwientek; Christiane Zarfl; Beate I. Escher. 2021. "Suspended Particulate Matter—A Source or Sink for Chemical Mixtures of Organic Micropollutants in a Small River under Baseflow Conditions?" Environmental Science & Technology 55, no. 8: 5106-5116.
Environmental factors contribute to the risk for adverse health outcomes against a background of genetic predisposition. Among these factors, chemical exposures may substantially contribute to disease risk and adverse outcomes. In fact, epidemiological cohort studies have established associations between exposure against individual chemicals and adverse health effects. Yet, in daily life individuals are exposed to complex mixtures in varying compositions. To capture the totality of environmental exposures the concept of the exposome has been developed. Here, we undertake an overview of major exposome projects, which pioneered the field of exposomics and explored the links between chemical exposure and health outcomes using cohort studies. We seek to reflect their achievements with regard to (i) capturing a comprehensive picture of the environmental chemical exposome, (ii) aggregating internal exposures using chemical and bioanalytical means of detection, and (iii) identifying associations that provide novel options for risk assessment and intervention. Various complementary approaches can be distinguished in addressing relevant exposure routes and it emerges that individual exposure histories may not easily be grouped. The number of chemicals for which human exposure can be detected is substantial and highlights the reality of mixture exposures. Yet, to a large extent it depends on targeted chemical analysis with the specific challenges to capture all relevant exposure routes and assess the chemical concentrations occurring in humans. The currently used approaches imply prior knowledge or hypotheses about relevant exposures. Typically, the number of chemicals considered in exposome projects is counted in dozens—in contrast to the several thousands of chemicals for which occurrence have been reported in human serum and urine. Furthermore, health outcomes are often still compared to single chemicals only. Moreover, explicit consideration of mixture effects and the interrelations between different outcomes to support causal relationships and identify risk drivers in complex mixtures remain underdeveloped and call for specifically designed exposome-cohort studies.
Sebastian Huhn; Beate I. Escher; Martin Krauss; Stefan Scholz; Jörg Hackermüller; Rolf Altenburger. Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive. Environmental Sciences Europe 2021, 33, 1 -20.
AMA StyleSebastian Huhn, Beate I. Escher, Martin Krauss, Stefan Scholz, Jörg Hackermüller, Rolf Altenburger. Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive. Environmental Sciences Europe. 2021; 33 (1):1-20.
Chicago/Turabian StyleSebastian Huhn; Beate I. Escher; Martin Krauss; Stefan Scholz; Jörg Hackermüller; Rolf Altenburger. 2021. "Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive." Environmental Sciences Europe 33, no. 1: 1-20.
Lili Niu; Eric Carmona; Maria König; Martin Krauss; Melis Muz; Chao Xu; Deliang Zou; Beate I. Escher. Correction to Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling. Environmental Science & Technology 2021, 55, 2171 -2171.
AMA StyleLili Niu, Eric Carmona, Maria König, Martin Krauss, Melis Muz, Chao Xu, Deliang Zou, Beate I. Escher. Correction to Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling. Environmental Science & Technology. 2021; 55 (3):2171-2171.
Chicago/Turabian StyleLili Niu; Eric Carmona; Maria König; Martin Krauss; Melis Muz; Chao Xu; Deliang Zou; Beate I. Escher. 2021. "Correction to Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling." Environmental Science & Technology 55, no. 3: 2171-2171.
Effect‐based trigger (EBT) values for in vitro bioassays are important for surface water quality monitoring because they define the threshold between acceptable and poor water quality. EBTs have been derived for highly specific bioassays, such as hormone‐receptor activation in reporter gene bioassays, by reading across from existing chemical guideline values. This read‐across method is not easily applicable to bioassays indicative of adaptive stress responses, which are triggered by many different chemicals, and activation of nuclear receptors for xenobiotic metabolism, to which many chemicals bind with rather low specificity. We propose an alternative approach to define the EBT from the distribution of specificity ratios of all active chemicals. Specificity ratios are the ratio between the predicted baseline toxicity of a chemical in a given bioassay and its measured specific endpoint. Unlike many previous read‐across methods to derive EBTs, the proposed method accounts for mixture effects and includes all chemicals, not only high‐potency chemicals. The EBTs were derived from a cytotoxicity EBT that was defined as equivalent to 1% of cytotoxicity in a native surface water sample. The cytotoxicity EBT was scaled by the median of the log‐normal distribution of specificity ratios to derive the EBT for effects specific for each bioassay. We illustrate the new approach using the example of the AREc32 assay indicative of the oxidative stress response and two nuclear receptor assays targeting the peroxisome proliferator activated receptor PPAR⃞ and the arylhydrocarbon receptor AhR. The EBTs were less conservative than previously proposed but were able to differentiate untreated and insufficiently treated wastewater from wastewater treatment plant effluent with secondary or tertiary treatment and surface water. This article is protected by copyright. All rights reserved.
Beate I. Escher; Peta A. Neale. Effect‐Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays. Environmental Toxicology and Chemistry 2020, 40, 487 -499.
AMA StyleBeate I. Escher, Peta A. Neale. Effect‐Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays. Environmental Toxicology and Chemistry. 2020; 40 (2):487-499.
Chicago/Turabian StyleBeate I. Escher; Peta A. Neale. 2020. "Effect‐Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays." Environmental Toxicology and Chemistry 40, no. 2: 487-499.
Sediment-associated risks depend on the bioavailable fraction of organic chemicals and cannot be comprehended by their total concentrations. The present study investigated contamination patterns of bioavailable chemicals in sediments from various sites around the globe by using passive equilibrium sampling. The extracts had been characterized previously for mixture effects by in vitro reporter gene assays and were in this study analyzed using gas chromatography-high resolution mass spectrometry for 121 chemicals including both legacy and emerging contaminants. The spatial distribution of the detected chemicals revealed distinct contamination patterns among sampling sites. We identified compounds in common at the different sites but most contaminant mixtures were site-specific. The mixture effects of the detected chemicals were predicted with a mixture toxicity model from effect concentrations of bioactive single chemicals and detected concentrations, applying a joint model for concentration addition and independent action. The predicted mixture effects were dominated by polycyclic aromatic hydrocarbons, and among the chemicals with available effect data, 17% elicited oxidative stress response and 18% activated the arylhydrocarbon receptor. Except for two sites in Sweden, where 11 and 38% of the observed oxidative stress response were explained by the detected chemicals, less than 10% of effects in both biological end points were explained. These results provide a comprehensive investigation of bioavailable contamination patterns of sediments and may serve as an example of employing passive equilibrium sampling as a monitoring technique to integrate the risk of bioavailable sediment-associated chemicals in aquatic environments.
Melis Muz; Beate I. Escher; Annika Jahnke. Bioavailable Environmental Pollutant Patterns in Sediments from Passive Equilibrium Sampling. Environmental Science & Technology 2020, 54, 15861 -15871.
AMA StyleMelis Muz, Beate I. Escher, Annika Jahnke. Bioavailable Environmental Pollutant Patterns in Sediments from Passive Equilibrium Sampling. Environmental Science & Technology. 2020; 54 (24):15861-15871.
Chicago/Turabian StyleMelis Muz; Beate I. Escher; Annika Jahnke. 2020. "Bioavailable Environmental Pollutant Patterns in Sediments from Passive Equilibrium Sampling." Environmental Science & Technology 54, no. 24: 15861-15871.
Concerns are increasing that pharmaceuticals released into the environment pose a risk to non‐target organism like fish. The fish plasma model (FPM) is a read‐across approach and uses human therapeutic blood plasma concentrations for estimating likely effects in fish. However, the FPM neglects differences in plasma protein binding between fish and humans. Since binding data for fish plasma are scarce, the binding of twelve active pharmaceutical ingredients (APIs, acidic, basic and neutral) to rainbow trout (Oncorhynchus mykiss) and human plasma was measured using solid‐phase microextraction (SPME). The plasma‐water distribution ratios (Dplasma/w) of neutral and basic APIs were similar for trout and human plasma, differing by not more than a factor of 2.7 per API. For the acidic APIs Dplasma/w of trout plasma were much lower than for human plasma, by up to a factor of 71 for naproxen. The lower affinity of the acidic APIs to trout plasma compared to human plasma suggests that the bioavailability of these APIs is higher in trout. Read‐across approaches like the FPM should account for differences in plasma protein binding to avoid over‐ or underestimation of effects in fish. For the acidic APIs, the effect ratio of the FPM would increase by a factor of 5 to 60 if the unbound plasma concentrations were used to calculate the effect ratio. Neutral and basic pharmaceuticals showed similar binding to trout and human blood plasma. Acidic pharmaceuticals (e.g., naproxen) bind to trout plasma with a lower affinity, suggesting a higher bioavailability of these pharmaceuticals in trout than in human plasma. This article is protected by copyright. All rights reserved.
Luise Henneberger; Nils Klüver; Marie Mühlenbrink; Beate Escher. Trout and Human Plasma Protein Binding of Selected Pharmaceuticals Informs the Fish Plasma Model. Environmental Toxicology and Chemistry 2020, 1 .
AMA StyleLuise Henneberger, Nils Klüver, Marie Mühlenbrink, Beate Escher. Trout and Human Plasma Protein Binding of Selected Pharmaceuticals Informs the Fish Plasma Model. Environmental Toxicology and Chemistry. 2020; ():1.
Chicago/Turabian StyleLuise Henneberger; Nils Klüver; Marie Mühlenbrink; Beate Escher. 2020. "Trout and Human Plasma Protein Binding of Selected Pharmaceuticals Informs the Fish Plasma Model." Environmental Toxicology and Chemistry , no. : 1.
The performance of an aerated horizontal subsurface flow treatment wetland was investigated before, during and after a simulated aeration failure. Conventional wastewater parameters (e.g., carbonaceous biological oxygen demand, total nitrogen, and Escherichia coli) as well as selected micropollutants (caffeine, ibuprofen, naproxen, benzotriazole, diclofenac, acesulfame, and carbamazepine) were investigated. Furthermore, the removal of biological effects was investigated using in vitro bioassays. The six bioassays selected covered environmentally relevant endpoints (indicative of activation of aryl hydrocarbon receptor, AhR; binding to the peroxisome proliferator-activated receptor gamma, PPARγ; activation of estrogen receptor alpha, ERα; activation of glucocorticoid receptor, GR; oxidative stress response, AREc32; combined algae test, CAT). During the aeration interruption phase, the water quality deteriorated to a degree comparable to that of a conventional (non-aerated) horizontal subsurface flow wetland. After the end of the aeration interruption, the analytical and biological parameters investigated recovered at different time periods until their initial treatment performance. Treatment efficacy for conventional parameters was recovered within a few days, but no complete recovery of treatment efficacy could be observed for bioassays AhR, AREc32 and CAT in the 21 days following re-start of the aeration system. Furthermore, the removal efficacy along the flow path for most of the chemicals and bioassays recovered as it was observed in the baseline phase. Only for the activation of AhR and AREc32 there was a shift of the internal treatment profile from 12.5% to 25% (AhR) and 50% (AREc32) of the fractional length.
Nadine Sossalla; Jaime Nivala; Beate Escher; Thorsten Reemtsma; Rita Schlichting; Manfred Van Afferden; Roland Müller. Resilience of Micropollutant and Biological Effect Removal in an Aerated Horizontal Flow Treatment Wetland. Water 2020, 12, 3050 .
AMA StyleNadine Sossalla, Jaime Nivala, Beate Escher, Thorsten Reemtsma, Rita Schlichting, Manfred Van Afferden, Roland Müller. Resilience of Micropollutant and Biological Effect Removal in an Aerated Horizontal Flow Treatment Wetland. Water. 2020; 12 (11):3050.
Chicago/Turabian StyleNadine Sossalla; Jaime Nivala; Beate Escher; Thorsten Reemtsma; Rita Schlichting; Manfred Van Afferden; Roland Müller. 2020. "Resilience of Micropollutant and Biological Effect Removal in an Aerated Horizontal Flow Treatment Wetland." Water 12, no. 11: 3050.
Storm events lead to agricultural and urban runoff, to mobilization of contaminated particulate matter and input from combined sewer overflows into rivers. We conducted time‐resolved sampling during a storm event at the Ammer River, Southwest Germany, which is representative for small river systems in densely populated areas of temperate climate. From two sampling sites suspended particulate matter (SPM) and water were separately analyzed by a multi‐analyte LC‐MS‐MS method for 97 environmentally relevant organic micropollutants and with two in‐vitro bioassays. Oxidative stress response (AREc32) may become activated by various stressors covering a broad range of physico‐chemical properties and aryl hydrocarbon receptor induction (AhR‐CALUX) by hydrophobic compounds such as dioxins and dioxin‐like molecules. Compound numbers, concentrations, their mass fluxes and associated effect fluxes increased substantially during the storm event. Micropollutants detected in water and on SPM pointed towards inputs from combined sewer overflow (e.g., caffeine, paracetamol), urban runoff (e.g., mecoprop, terbutryn) and agricultural areas (e.g., azoxystrobin, bentazone). Particle‐facilitated transport of triphenylphosphate and tris(1‐chloro‐2‐propyl) phosphate accounted for up to 34 and 33% of the total mass flux despite SPM concentrations below 1 g L‐1. Effect fluxes attributed to SPM were similar or higher than in the water phase. The important role of SPM‐bound transport emphasizes the need to consider not only concentrations but also mass and effect fluxes for surface water quality assessment and wastewater/stormwater treatment options. This article is protected by copyright. All rights reserved.
Maximilian E. Müller; Christian Zwiener; Beate I. Escher. Storm Event–Driven Occurrence and Transport of Dissolved and Sorbed Organic Micropollutants and Associated Effects in the Ammer River, Southwestern Germany. Environmental Toxicology and Chemistry 2020, 40, 88 -99.
AMA StyleMaximilian E. Müller, Christian Zwiener, Beate I. Escher. Storm Event–Driven Occurrence and Transport of Dissolved and Sorbed Organic Micropollutants and Associated Effects in the Ammer River, Southwestern Germany. Environmental Toxicology and Chemistry. 2020; 40 (1):88-99.
Chicago/Turabian StyleMaximilian E. Müller; Christian Zwiener; Beate I. Escher. 2020. "Storm Event–Driven Occurrence and Transport of Dissolved and Sorbed Organic Micropollutants and Associated Effects in the Ammer River, Southwestern Germany." Environmental Toxicology and Chemistry 40, no. 1: 88-99.
The identification of mixture risk drivers is a great challenge for sediment assessment, especially when taking bioavailability into consideration. The bioavailable portion, which comprises the organic contaminants in pore water and the ones bound to organic carbon, was accessed by equilibrium partitioning to polydimethylsiloxane (PDMS). The exhaustive solvent and PDMS extracts were toxicologically characterized with a battery of in vitro reporter gene assays and chemically analyzed with liquid and gas chromatography coupled to high-resolution mass spectrometry. The bioavailable fractions of mixture effects and individual chemicals were mostly lower than 0.1, indicating that more than 90% of the substances are strongly bound and would not pose an immediate risk but could potentially be remobilized in the long term. Despite 655 organic chemicals analyzed, only 0.1%-28% of the observed biological effects was explained by the detected compounds in whole sediments, while 0.009%-3.3% was explained by bioavailable chemicals. The mixture effects were not only dominated by legacy pollutants (e.g., polycyclic aromatic hydrocarbon (PAHs) in the bioassay for activation of the aryl-hydrocarbon receptor (AhR) and oxidative stress response (AREc32)), but also by present-use chemicals (e.g., plastic additives for binding to the peroxisome proliferator-activated receptor γ (PPARγ)), with different fingerprints between whole sediments and bioavailable extracts. Our results highlight the necessity to involve different bioassays with diverse effect profiles and broader selection of contaminants along with bioavailability for the risk assessment of chemical mixtures in sediments.
Lili Niu; Eric Carmona; Maria König; Martin Krauss; Melis Muz; Chao Xu; Deliang Zou; Beate I. Escher. Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling. Environmental Science & Technology 2020, 54, 13197 -13206.
AMA StyleLili Niu, Eric Carmona, Maria König, Martin Krauss, Melis Muz, Chao Xu, Deliang Zou, Beate I. Escher. Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling. Environmental Science & Technology. 2020; 54 (20):13197-13206.
Chicago/Turabian StyleLili Niu; Eric Carmona; Maria König; Martin Krauss; Melis Muz; Chao Xu; Deliang Zou; Beate I. Escher. 2020. "Mixture Risk Drivers in Freshwater Sediments and Their Bioavailability Determined Using Passive Equilibrium Sampling." Environmental Science & Technology 54, no. 20: 13197-13206.
The combined algae test (CAT) is a 96‐well plate‐based algal toxicity assay with the green algae Raphidocelis subcapitata that combines inhibition of 24h population growth rate with inhibition of photosynthesis detected after 2h and 24h with pulse‐amplitude modulated (PAM) fluorometry using a Maxi‐Imaging PAM. The CAT has been in use for more than a decade but had limitations due to incompatibilities of the measurements of the two biological endpoints on the same microtiter plates. These limitations could be overcome by increasing growth rates and doubling times on black, clear‐bottom 96‐well plates by application of dichromatic red/blue LED illumination. Different robotic dosing approaches and additional data evaluation approaches helped to further expand the applicability domain of the assay. The CAT differentiates between non‐specifically acting compounds and photosynthesis inhibitors, such as photosystem II (PSII)‐herbicides. PSII‐herbicides acted immediately on photosynthesis and showed growth rate inhibition at higher concentrations. If growth was a similar or more sensitive endpoint than photosynthesis inhibition, this was an indication that the tested chemical acted non‐specifically or a mixture or a water sample was dominated by chemicals other than PSII‐herbicides acting on algal growth. We fingerprinted the effects of 45 chemicals on photosynthesis inhibition and growth rate and related the effects of the single compounds to designed mixtures of these chemicals detected in water samples and to the effects directly measured in water samples. Most of the observed effects in the water samples could be explained by known photosystem II inhibitors such as triazines and phenylurea herbicides. The improved setup of the CAT gave consistent results with the previous method but has lower cost, higher throughput and higher precision.
Lisa Glauch; Beate I. Escher. The Combined Algae Test for the Evaluation of Mixture Toxicity in Environmental Samples. Environmental Toxicology and Chemistry 2020, 39, 2496 -2508.
AMA StyleLisa Glauch, Beate I. Escher. The Combined Algae Test for the Evaluation of Mixture Toxicity in Environmental Samples. Environmental Toxicology and Chemistry. 2020; 39 (12):2496-2508.
Chicago/Turabian StyleLisa Glauch; Beate I. Escher. 2020. "The Combined Algae Test for the Evaluation of Mixture Toxicity in Environmental Samples." Environmental Toxicology and Chemistry 39, no. 12: 2496-2508.
Chemicals emitted into the environment are typically present at low concentrations but may act together in mixtures. Concentration‐response curves of in vitro bioassays were often linear <30% effect and the predictions for concentration addition (CA) of similarly acting chemicals and for independent action (IA) of dissimilarly acting chemicals overlapped. We derived a joint CA/IA mixture model for the low‐effect level portion of concentration‐response curves. In a first case study, we evaluated the cytotoxicity of over 200 mixtures of up to 17 components that were mixed in concentration ratios as they occurred in river water. The predictions of the full IA model were indistinguishable from the predictions of the full CA model up to the 10% effect level confirming the applicability of the joint CA/IA mixture model at low effect levels. In a second case study, we evaluated if environmental concentrations trigger effects at levels low enough for the joint CA/IA mixture model to apply. The detected concentrations were scaled by their toxic potencies to estimate the mixture effect of the detected chemicals in a complex mixture. In 86% of 156 samples the effects fell in the validity range of the joint CA/IA mixture model (<10% effect level) confirming the CA assumption for toxic unit summation. The joint CA/IA mixture model is not suitable for testing specific mixture hypotheses and interactions of chemicals in mixtures, where more refined models are required, but it is helpful for the interpretation of effects of complex (multicomponent) environmental mixtures, especially for water samples with relatively low effect level. This article is protected by copyright. All rights reserved.
Beate Escher; Georg Braun; Christiane Zarfl. Exploring the Concepts of Concentration Addition and Independent Action Using a Linear Low‐Effect Mixture Model. Environmental Toxicology and Chemistry 2020, 39, 2552 -2559.
AMA StyleBeate Escher, Georg Braun, Christiane Zarfl. Exploring the Concepts of Concentration Addition and Independent Action Using a Linear Low‐Effect Mixture Model. Environmental Toxicology and Chemistry. 2020; 39 (12):2552-2559.
Chicago/Turabian StyleBeate Escher; Georg Braun; Christiane Zarfl. 2020. "Exploring the Concepts of Concentration Addition and Independent Action Using a Linear Low‐Effect Mixture Model." Environmental Toxicology and Chemistry 39, no. 12: 2552-2559.
Background:High-throughput screening of chemicals with in vitro reporter gene assays in Tox21 has produced a large database on cytotoxicity and specific modes of action. However, the validity of some of the reported activities is questionable due to the “cytotoxicity burst,” which refers to the supposition that many stress responses are activated in a nonspecific way at concentrations close to cell death.Objectives:We propose a pragmatic method to identify whether reporter gene activation is specific or cytotoxicity-triggered by comparing the measured effects with baseline toxicity.Methods:Baseline toxicity, also termed narcosis, is the minimal toxicity any chemical causes. Quantitative structure–activity relationships (QSARs) developed for baseline toxicity in mammalian reporter gene cell lines served as anchors to define the chemical-specific threshold for the cytotoxicity burst and to evaluate the degree of specificity of the reporter gene activation. Measured 10% effect concentrations were related to measured or QSAR-predicted 10% cytotoxicity concentrations yielding specificity ratios (SR). We applied this approach to our own experimental data and to ∼8,000 chemicals that were tested in six of the high-throughput Tox21 reporter gene assays.Results:Confirmed baseline toxicants activated reporter gene activity around cytotoxic concentrations triggered by the cytotoxicity burst. In six Tox21 assays, 37%–87% of the active hits were presumably caused by the cytotoxicity burst (SR<1) and only 2%–14% were specific with SR≥10 against experimental cytotoxicity but 75%–97% were specific against baseline toxicity. This difference was caused by a large fraction of chemicals showing excess cytotoxicity.Conclusions:The specificity analysis for measured in vitro effects identified whether a cytotoxicity burst had likely occurred. The SR-analysis not only prevented false positives, but it may also serve as measure for relative effect potency and can be used for quantitative in vitro–in vivo extrapolation and risk assessment of chemicals. https://doi.org/10.1289/EHP6664
Beate I. Escher; Luise Henneberger; Maria König; Rita Schlichting; Fabian C. Fischer. Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays. Environmental Health Perspectives 2020, 128, 077007 .
AMA StyleBeate I. Escher, Luise Henneberger, Maria König, Rita Schlichting, Fabian C. Fischer. Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays. Environmental Health Perspectives. 2020; 128 (7):077007.
Chicago/Turabian StyleBeate I. Escher; Luise Henneberger; Maria König; Rita Schlichting; Fabian C. Fischer. 2020. "Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays." Environmental Health Perspectives 128, no. 7: 077007.
Peta A. Neale; Georg Braun; Werner Brack; Eric Carmona; Roman Gunold; Maria König; Martin Krauss; Liana Liebmann; Matthias Liess; Moritz Link; Ralf Schäfer; Rita Schlichting; Verena C. Schreiner; Tobias Schulze; Philipp Vormeier; Oliver Weisner; Beate I. Escher. Assessing the Mixture Effects in In Vitro Bioassays of Chemicals Occurring in Small Agricultural Streams during Rain Events. Environmental Science & Technology 2020, 54, 8280 -8290.
AMA StylePeta A. Neale, Georg Braun, Werner Brack, Eric Carmona, Roman Gunold, Maria König, Martin Krauss, Liana Liebmann, Matthias Liess, Moritz Link, Ralf Schäfer, Rita Schlichting, Verena C. Schreiner, Tobias Schulze, Philipp Vormeier, Oliver Weisner, Beate I. Escher. Assessing the Mixture Effects in In Vitro Bioassays of Chemicals Occurring in Small Agricultural Streams during Rain Events. Environmental Science & Technology. 2020; 54 (13):8280-8290.
Chicago/Turabian StylePeta A. Neale; Georg Braun; Werner Brack; Eric Carmona; Roman Gunold; Maria König; Martin Krauss; Liana Liebmann; Matthias Liess; Moritz Link; Ralf Schäfer; Rita Schlichting; Verena C. Schreiner; Tobias Schulze; Philipp Vormeier; Oliver Weisner; Beate I. Escher. 2020. "Assessing the Mixture Effects in In Vitro Bioassays of Chemicals Occurring in Small Agricultural Streams during Rain Events." Environmental Science & Technology 54, no. 13: 8280-8290.
Exposure assessment in in vitro cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecular interactions. Total medium concentrations (Ctotal,medium) and/or freely dissolved medium concentrations (Cfree,medium) were determined for one neutral chemical and 14 IOCs (acids, bases, multifunctional) at concentrations relevant for determination of cytotoxicity and effect. Cfree,medium were measured in two in vitro bioassays at the time of dosing and after 24 h of incubation using solid-phase microextraction (SPME). Cfree,medium were maximally 1.7 times lower than the nominal concentrations (Cnom) for the hydrophilic chemicals (caffeine and lamotrigine). For the organic acids (naproxen, ibuprofen, warfarin and diclofenac), Cfree,medium was by a factor of 4 lower than Cnom at high concentrations but the ratio was much higher at low concentrations, indicating a non-linear binding behavior. The experimental Cfree,medium were also compared with Cfree,medium predicted with a mass balance model accounting for binding to medium proteins and lipids. The mass balance model performed well for five of the test chemicals (within a factor of 10) but it underestimated Cfree,medium by up to a factor of 1200 for chemicals that showed non-linear binding to medium components. These findings emphasize that experimental exposure assessment is required for improved understanding of in vitro toxicity data.
Julia Huchthausen; Marie Mühlenbrink; Maria König; Beate I. Escher; Luise Henneberger. Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays. Chemical Research in Toxicology 2020, 33, 1845 -1854.
AMA StyleJulia Huchthausen, Marie Mühlenbrink, Maria König, Beate I. Escher, Luise Henneberger. Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays. Chemical Research in Toxicology. 2020; 33 (7):1845-1854.
Chicago/Turabian StyleJulia Huchthausen; Marie Mühlenbrink; Maria König; Beate I. Escher; Luise Henneberger. 2020. "Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays." Chemical Research in Toxicology 33, no. 7: 1845-1854.
Organic micropollutants of anthropogenic origin in river waters may impair aquatic ecosystem health and drinking water quality. To evaluate micropollutant fate and turnover on a catchment scale, information on input source characteristics as well as spatial and temporal variability are required. The influence of tributaries from agricultural and urban areas and the input of wastewater were investigated by grab and Lagrangian sampling under base flow conditions within a 7.7 km long stretch of the Ammer River (Southwest Germany) using target screening for 83 organic micropollutants and four in‐vitro bioassays with environmentally relevant modes of action. In total 9 pesticides and transformation products, 13 pharmaceuticals and 6 industrial and household chemicals were detected. Further, aryl hydrocarbon receptor induction, peroxisome proliferator‐activated receptor activity, estrogenicity and oxidative stress response was measured in the river. The vast majority of the compounds and mixture effects were introduced by the effluent of a wastewater treatment plant, which contributed 50% of the total flow rate of the river on the sampling day. The tributaries contributed little to the overall load of organic micropollutants and mixture effects due to their relatively low discharge but showed a different chemical and toxicological pattern than the Ammer River. Though, a comparison to effect‐based trigger values pointed towards unacceptable surface water quality in the main stem and in some of the tributaries. Chemical analysis and in‐vitro bioassays covered different windows of analyte properties but reflected the same picture. This article is protected by copyright. All rights reserved.
Maximilian E. Müller; Martina Werneburg; Clarissa Glaser; Marc Schwientek; Christiane Zarfl; Beate I. Escher; Christian Zwiener. Influence of Emission Sources and Tributaries on the Spatial and Temporal Patterns of Micropollutant Mixtures and Associated Effects in a Small River. Environmental Toxicology and Chemistry 2020, 39, 1382 -1391.
AMA StyleMaximilian E. Müller, Martina Werneburg, Clarissa Glaser, Marc Schwientek, Christiane Zarfl, Beate I. Escher, Christian Zwiener. Influence of Emission Sources and Tributaries on the Spatial and Temporal Patterns of Micropollutant Mixtures and Associated Effects in a Small River. Environmental Toxicology and Chemistry. 2020; 39 (7):1382-1391.
Chicago/Turabian StyleMaximilian E. Müller; Martina Werneburg; Clarissa Glaser; Marc Schwientek; Christiane Zarfl; Beate I. Escher; Christian Zwiener. 2020. "Influence of Emission Sources and Tributaries on the Spatial and Temporal Patterns of Micropollutant Mixtures and Associated Effects in a Small River." Environmental Toxicology and Chemistry 39, no. 7: 1382-1391.