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1.
Chemosphere ; 279: 130424, 2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33887594

RESUMEN

A novel active sampling method enabled determination of sediment depth profiles revealing the spatial distribution of model compounds N,N-dimethylsulfamide, fluopyram and bixafen (low, medium, high adsorption affinity) in sediment microcosms according to OECD Test 218/219 (Sediment-Water Chironomid Toxicity Test Using Spiked Sediment/Spiked Water). After the overlying water was removed, plastic tubes were inserted into the sediment and the microcosms were frozen. For depth-related analysis, each "sediment core" was mounted in a cutting device and sawed into three 5-mm-slices, respectively (top, middle, bottom). Each slice was centrifuged for sediment and pore water separation. By various sampling dates within 28 days, we could follow the behavior of model compounds depending on sorption affinities and display specific distribution patterns within the sediment. N,N-dimethylsulfamide showing no sediment adsorption, migrated unhindered in (OECD 219) and out (OECD 218) of the sediment via pore water, resulting in homogenous distributions in both test designs. Fluopyram with moderate adsorption affinity revealed a concentration gradient with declining amounts from top to bottom layer (OECD 219) and higher amounts in the middle and bottom layer as compared to the top layer (OECD 218). Bixafen providing a strong adsorption affinity accumulated in the top layer in OECD 219, while no concentration gradients became visible in OECD 218. For establishing a Toxic Substances in Surface Waters (TOXSWA) model, we compared our measurements with simulated results revealing good agreements. The presented methodology is a useful tool to determine more realistic sediment and pore water concentrations, which the Chironomid larvae are exposed to.

2.
Environ Sci Technol ; 55(9): 5620-5628, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33851533

RESUMEN

For decades, we have known that chemicals affect human and wildlife behavior. Moreover, due to recent technological and computational advances, scientists are now increasingly aware that a wide variety of contaminants and other environmental stressors adversely affect organismal behavior and subsequent ecological outcomes in terrestrial and aquatic ecosystems. There is also a groundswell of concern that regulatory ecotoxicology does not adequately consider behavior, primarily due to a lack of standardized toxicity methods. This has, in turn, led to the exclusion of many behavioral ecotoxicology studies from chemical risk assessments. To improve understanding of the challenges and opportunities for behavioral ecotoxicology within regulatory toxicology/risk assessment, a unique workshop with international representatives from the fields of behavioral ecology, ecotoxicology, regulatory (eco)toxicology, neurotoxicology, test standardization, and risk assessment resulted in the formation of consensus perspectives and recommendations, which promise to serve as a roadmap to advance interfaces among the basic and translational sciences, and regulatory practices.

3.
Ecotoxicol Environ Saf ; 214: 112092, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33690008

RESUMEN

Over the last two decades, effect-directed analysis (EDA) gained importance as a seminal screening tool for tracking biological effects of environmental organic micro-pollutants (MPs). As EDA using high-performance liquid chromatography and bioassays is costly and time consuming, recent implementations of this approach have combined high-performance thin-layer chromatography (HPTLC) with effect-based methods (EBMs) using cell-based bioassays, enabling the detection of estrogenic, androgenic, genotoxic, photosystem II (PSII)- inhibiting, and dioxin-like sample components on a HPTLC plate. In the present study, the developed methodologies were applied as a HPTLC-based bioassay battery, to investigate toxicant elimination efficiency of wastewater treatment plants (WWTPs), and to characterize the toxic potential of landfill leachates. Activity levels detected in untreated landfill leachates, expressed as reference compound equivalence (EQ) concentration, were up to 16.8 µg ß-naphthoflavone-EQ L-1 (indicating the degree of dioxin-like activity), 1.9 µg estradiol-EQ L-1 (estrogenicity) and 8.3 µg diuron-EQ L­1 (PSII-inhibition), dropping to maximal concentrations of 47 ng ß-naphthoflavone-EQ L-1, 0.7 µg estradiol-EQ L-1 and 53.1 ng diuron-EQ L-1 following treatment. Bisphenol A (BPA) is suggested to be the main contributor to estrogenic activity, with concentrations determined by the planar yeast estrogen screen corresponding well to results from chemical analysis. In the investigated WWTP samples, a decrease of estrogenic activity of 6-100% was observed following treatment for most of the active fractions, except of a 20% increase in one fraction (Rf = 0.568). In contrast, androgenicity with concentrations up to 640 ng dihydrotestosterone-EQ L-1 was completely removed by treatment. Interestingly, genotoxic activity increased over the WWTP processes, releasing genotoxic fractions into receiving waters. We propose this combined HPTLC and EBM battery to contribute to an efficient, cheap, fast and robust screening of environmental samples; such an assay panel would allow to gain an estimate of potential biological effects for prioritization prior to substance identification, and its routine application will support an inexpensive identification of the toxicity drivers as a first tier in an EDA strategy.


Asunto(s)
Bioensayo/métodos , Contaminantes Químicos del Agua/toxicidad , Purificación del Agua , Compuestos de Bencidrilo , Cromatografía en Capa Delgada/métodos , Monitoreo del Ambiente/métodos , Estrógenos/toxicidad , Fenoles , Dibenzodioxinas Policloradas/análisis , Aguas Residuales/análisis , beta-naftoflavona
4.
Sci Total Environ ; 764: 142902, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33757253

RESUMEN

To avoid potential risks of biofuels on the environment and human, ecotoxicity investigation should be integrated into the early design stage for promising biofuel candidates. In the present study, a green toxicology testing strategy combining experimental bioassays with in silico tools was established to investigate the potential ecotoxicity of biofuel candidates. Experimental results obtained from the acute immobilisation test, the fish embryo acute toxicity test and the in vitro micronucleus assay (Chinese hamster lung fibroblast cell line V79) were compared with model prediction results by ECOSAR and OECD QSAR Toolbox. Both our experimental and model prediction results showed that 1-Octanol (1-Oct) and Di-n-butyl ether (DNBE) were the most toxic to Daphnia magna and zebrafish among all the biofuel candidates we investigated, while Methyl ethyl ketone (MEK), Dimethoxymethane (DMM) and Diethoxymethane (DEM) were the least toxic. Moreover, both in vitro micronucleus assay and OECD QSAR Toolbox evaluation suggested that the metabolites present higher genotoxicity than biofuel candidates themselves. Overall, our results proved that this green toxicology testing strategy is a useful tool for assessing ecotoxicity of biofuel candidates.


Asunto(s)
Biocombustibles , Contaminantes Químicos del Agua , Animales , Biocombustibles/toxicidad , Línea Celular , Cricetinae , Daphnia , Humanos , Pruebas de Toxicidad Aguda , Pez Cebra
5.
Environ Pollut ; 277: 116795, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33640813

RESUMEN

Investigating environmental pollution is important to understand its impact on endangered species such as green turtles (Chelonia mydas). In this study, we investigated the accumulation and potential toxicity of selected persistent organic pollutants (POPs) and naturally occurring MeO-PBDEs in liver, fat, kidney and muscle of turtles (n = 30) of different gender, size, year of death, location and health status. Overall, POP concentrations were low and accumulation was highest in liver and lowest in fat which is likely due to the poor health of several animals, causing a remobilization of lipids and associated compounds. PCBs and p,p'-DDE dominated the POP profiles, and relatively high MeO-PBDE concentrations (2'-MeO-BDE 68 up to 192 ng/g lw, 6-MeO-BDE 47 up to 79 ng/g lw) were detected in all tissues. Only few influences of factors such as age, gender and location were found. While concentrations were low compared to other marine wildlife, biological toxicity equivalences obtained by screening the tissue extracts using the micro-EROD assay ranged from 2.8 to 356 pg/g and the highest values were observed in muscle, followed by kidney and liver. This emphazises that pollutant mixtures found in the turtles have the potential to cause dioxin-like effects in these animals and that dioxin-like compounds should not be overlooked in future studies.


Asunto(s)
Bifenilos Policlorados , Tortugas , Contaminantes Químicos del Agua , Animales , Monitoreo del Ambiente , Éteres Difenilos Halogenados/toxicidad , Bifenilos Policlorados/toxicidad , Contaminantes Químicos del Agua/toxicidad
6.
Sci Total Environ ; 769: 144324, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33482551

RESUMEN

Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany. We distinguished and evaluated four dominant stressor categories along this gradient: (1) Hydromorphological alterations: Flow diversity and substrate diversity correlated with the EU-Water Framework Directive based indicators for the quality element macroinvertebrates, which deteriorated at the transition from near-natural reference sites to urban sites. (2) Elevated nutrient levels and eutrophication: Low to moderate nutrient concentrations together with complete canopy cover at the reference sites correlated with low densities of benthic algae (biofilms). We found no more systematic relation of algal density with nutrient concentrations at the downstream sites, suggesting that limiting concentrations are exceeded already at moderate nutrient concentrations and reduced shading by riparian vegetation. (3) Elevated organic matter levels: Wastewater treatment plants (WWTP) and stormwater drainage systems were the primary sources of bioavailable dissolved organic carbon. Consequently, planktonic bacterial production and especially extracellular enzyme activity increased downstream of those effluents showing local peaks. (4) Micropollutants and toxicity-related stress: WWTPs were the predominant source of toxic stress, resulting in a rapid increase of the toxicity for invertebrates and algae with only one order of magnitude below the acute toxic levels. This toxicity correlates negatively with the contribution of invertebrate species being sensitive towards pesticides (SPEARpesticides index), probably contributing to the loss of biodiversity recorded in response to WWTP effluents. Our longitudinal approach highlights the potential of coordinated community efforts in supplementing established monitoring methods to tackle the complex phenomenon of multiple stress.

7.
Ecotoxicol Environ Saf ; 208: 111716, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396047

RESUMEN

Although withdrawn from the market in the 1980s, polychlorinated biphenyls (PCBs) are still found ubiquitously in the aquatic environment and pose a serious risk to biota due to their teratogenic potential. In fish, early life-stages are often considered most sensitive with regard to their exposure to PCBs and other dioxin-like compounds. However, little is known about the molecular drivers of the frequently observed teratogenic effects. Therefore, the aims of our study were to: (1) characterize the baseline transcriptome profiles at different embryonic life-stages in zebrafish (Danio rerio); and (2) to identify the molecular response to PCB exposure and life-stage specific-effects of the chemical on associated processes. For both objectives, embryos were sampled at 12, 48, and 96 h post-fertilization (hpf) and subjected to Illumina sequence-by-synthesis and RNAseq analysis. Results revealed that with increasing age more genes and related pathways were upregulated both in terms of number and magnitude. Yet, other transcripts followed an opposite pattern with greater transcript abundance at the earlier time points. Additionally, embryos were exposed to PCB126, a potent agonist of the aryl hydrocarbon receptor (AHR). ClueGO network analysis revealed significant enrichment of genes associated with basic cell metabolism, communication, and homeostasis as well as eye development, muscle formation, and skeletal formation. We selected eight genes involved in the affected pathways for an in-depth characterization of their regulation throughout normal embryogenesis and after exposure to PCB126 by quantification of transcript abundances every 12 h until 118 hpf. Among these, fgf7 and c9 stood out because of their strong upregulation by PCB126 exposure at 48 and 96 hpf, respectively. Cyp2aa12 was upregulated from 84 hpf on. Fabp10ab, myhz1.1, col8a1a, sulf1, and opn1sw1 displayed specific regulation depending on the developmental stage. Overall, we demonstrate that (1) the developmental transcriptome of zebrafish is highly dynamic, and (2) dysregulation of gene expression by exposure to PCB126 was significant and in several cases not directly connected to AHR-signaling. Hence, this study improves the understanding of linkages between molecular events and apical outcomes that are of regulatory relevance.


Asunto(s)
Desarrollo Embrionario/efectos de los fármacos , Bifenilos Policlorados/toxicidad , Teratógenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/embriología , Animales , Embrión no Mamífero/efectos de los fármacos , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Transcriptoma , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/antagonistas & inhibidores
8.
Sci Total Environ ; 751: 142269, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33182016

RESUMEN

This study presents a high-throughput (HTP) micronucleus assay in multi-well plates with an automated evaluation for risk assessment applications. The evaluation of genotoxicity via the micronucleus assays according to international guidelines ISO 21427-2 with Chinese hamster (Cricetulus griseus) V79 cells was the starting point to develop our methodology. A drawback of this assay is that it is very time consuming and cost intensive. Our HTP micronucleus assay in a 48-well plate format allows for the simultaneous assessment of five different sample-concentrations with additional positive, negative and solvent controls with six technical replicates each within a quarter of the time required for the equivalent evaluation using the traditional slide method. In accordance with the 3R principle, animal compounds should be replaced with animal-free alternatives. However, traditional cell culture-based methods still require animal derived compounds like rat-liver derived S9-fraction, which is used to simulate the mammalian metabolism in in vitro assays that do show intrinsic metabolization capabilities. In the present study, a recently developed animal-free biotechnological alternative (ewoS9R) was investigated in the new high-throughput micronucleus assay. In total, 12 different mutagenic or genotoxic chemicals were investigated to assess the potential use of the animal-free metabolization system (ewoS9R) in comparison to a common rat-derived product. Out of the 12 compounds, one compound did not induce micronuclei in any treatment and 2 substances showed a genotoxic potential without the need for a metabolization system. EwoS9R demonstrated promising potential for future applications as it shows comparable results to the rat-derived S9 for 6 of the 9 pro-genotoxic substances tested. The remaining 3 substances (2-Acetamidofluorene, Benzo[a]pyrene, Cyclophosphamide) were only metabolized by rat-derived S9. A potential explanation is that ewoS9R was investigated with an approx. 10-fold lower enzyme concentration and was only optimized for CYP1A metabolization that may be improved with a modified production procedure. Future applications of ewoS9R go beyond the micronucleus assay, but further research is necessary.


Asunto(s)
Benzo(a)pireno , Mutágenos , Animales , Línea Celular , Cricetinae , Ciclofosfamida , Pruebas de Micronúcleos , Mutágenos/toxicidad , Ratas
9.
Sci Total Environ ; 758: 143891, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33338786

RESUMEN

Flooding and other sediment disturbances can lead to increases in sediment resuspension. In this context, it is of central importance to understand the kinetics of release from these sediments and the uptake of pollutants, such as polychlorinated biphenyls (PCBs) and polychlorinated dioxins and furans (PCDD/Fs), into aquatic organisms. In the present study, we parameterized a sediment desorption model based on experimentally determined rapidly-desorbing fractions of dioxin-like chemicals (DLCs). We coupled this desorption model with a physiologically-based toxicokinetic model for rainbow trout. This combined model was used to predict DLC concentrations in the muscle of exposed fish. The performance of this model was evaluated using a previously published dataset on DLC uptake from sediment suspensions during simulated re-suspension events. Predictions generally differed less than 10-fold from measured values, and the model showed a good global coefficient of determination (R2) of 0.95. The root mean squared error (RMSE) for PCBs was 0.31 log units and 0.53 log units for PCDD/Fs. The results of our study demonstrate that the prediction of bioconcentration and related risk to fish resulting from sediment resuspension can be accurately predicted using coupled desorption and toxicokinetic models.


Asunto(s)
Dioxinas , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animales , Bioacumulación , Dibenzofuranos , Dibenzofuranos Policlorados , Sedimentos Geológicos , Bifenilos Policlorados/análisis
10.
Sci Total Environ ; 757: 144188, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33316512

RESUMEN

This special issue of STOTEN is dedicated to presenting the results of the WWF-Australia "Rivers to Reef to Turtles" project, which focused on investigating pollutants in the environment, food and bodies of green turtles (Chelonia mydas) on the Great Barrier Reef (GBR). The project brought together organic and inorganic trace chemical analysis, bioanalytical tools and individual health monitoring to investigate potential causes of an unusual mortality event in 2012. Together, the ten studies in this special issue highlight the shortcomings of current chemical monitoring and impact assessment programmes, which are focused on a limited number of prioritised chemicals and fail to account for the incredible diversity of toxicants released by human activities. It is essential that future management efforts consider the impact of these contaminants on the GBR, already under threat from global warming and sediment and nutrient runoff. Understanding the impact that chemical contaminants have on turtles not only informs green turtle conservation but can also, as they are sensitive and long-lived bioindicators of environmental health, guide efforts to protect, conserve and restore marine ecosystems such as the GBR.


Asunto(s)
Tortugas , Contaminantes Químicos del Agua , Animales , Australia , Ecosistema , Monitoreo del Ambiente , Ríos , Contaminantes Químicos del Agua/análisis
11.
Sci Total Environ ; 751: 141750, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32861187

RESUMEN

Wastewater-based monitoring of the spread of the new SARS-CoV-2 virus, also referred to as wastewater-based epidemiology (WBE), has been suggested as a tool to support epidemiology. An extensive sampling campaign, including nine municipal wastewater treatment plants, has been conducted in different cities of the Federal State of North Rhine-Westphalia (Germany) on the same day in April 2020, close to the first peak of the corona crisis. Samples were processed and analysed for a set of SARS-CoV-2-specific genes, as well as pan-genotypic gene sequences also covering other coronavirus types, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, a comprehensive set of chemical reference parameters and bioindicators was analysed to characterize the wastewater quality and composition. Results of the RT-qPCR based gene analysis indicate the presence of SARS-CoV-2 genetic traces in different raw wastewaters. Furthermore, selected samples have been sequenced using Sanger technology to confirm the specificity of the RT-qPCR and the origin of the coronavirus. A comparison of the particle-bound and the dissolved portion of SARS-CoV-2 virus genes shows that quantifications must not neglect the solid-phase reservoir. The infectivity of the raw wastewater has also been assessed by viral outgrowth assay with a potential SARS-CoV-2 host cell line in vitro, which were not infected when exposed to the samples. This first evidence suggests that wastewater might be no major route for transmission to humans. Our findings draw attention to the need for further methodological and molecular assay validation for enveloped viruses in wastewater.


Asunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Aguas Residuales , Betacoronavirus , Ciudades , Alemania/epidemiología , Humanos
12.
Aquat Toxicol ; 231: 105719, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360234

RESUMEN

Numerous environmental pollutants have the potential to accumulate in sediments, and among them are endocrine-disrupting chemicals (EDCs). It is well documented that water-borne exposure concentrations of some potent EDCs, more specifically estrogenic- active compounds (ECs), can impair the reproduction of fish. In contrast, little is known about the bioavailability and effects of sediment-associated ECs on fish. Particularly, when sediments are disturbed, e.g., during flood events, chemicals may be released from the sediment and become bioavailable. The main objectives of this study were to evaluate a) whether ECs from the sediment become bioavailable to fish when the sediment is suspended, and b) whether such exposure leads to endocrine responses in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were exposed over 21 days to constantly suspended sediments in the following treatments: i) a contaminated sediment from the Luppe River, representing a "hotspot" for EC accumulation, ii) a reference sediment (exhibiting only background contamination), iii) three dilutions, 2-, 4- and 8-fold of Luppe sediment diluted with the reference sediment, and iv) a water-only control. Measured estrogenic activity using in vitro bioassays as well as target analysis of nonylphenol and estrone via LC-MS/MS in sediment, water, fish plasma, as well as bile samples, confirmed that ECs became bioavailable from the sediment during suspension. ECs were dissolved in the water phase, as indicated by passive samplers, and were readily taken up by the exposed trout. An estrogenic response of fish to Luppe sediment was indicated by increased abundance of transcripts of typical estrogen responsive genes, i.e. vitelline envelope protein α in the liver and vitellogenin induction in the skin mucus. Altered gene expression profiles of trout in response to suspended sediment from the Luppe River suggest that in addition to ECs a number of other contaminants such as dioxins, polychlorinated biphenyls (PCBs) and heavy metals were remobilized during suspension. The results of the present study demonstrated that sediments not only function as a sink for ECs but can turn into a significant source of pollution when sediments are resuspended as during flood-events. This highlights the need for sediment quality criteria considering bioavailability sediment-bound contaminants in context of flood events.


Asunto(s)
Estrógenos/toxicidad , Sedimentos Geológicos/química , Oncorhynchus mykiss/metabolismo , Animales , Disponibilidad Biológica , Exposición a Riesgos Ambientales , Femenino , Ontología de Genes , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Vitelogeninas/metabolismo , Contaminantes Químicos del Agua/toxicidad
13.
Sci Total Environ ; 760: 143914, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33333401

RESUMEN

Endocrine disruption (ED) can trigger far-reaching effects on environmental populations, justifying a refusal of market approval for chemicals with ED properties. For the hazard assessment of ED effects on the thyroid system, regulatory decisions mostly rely on amphibian studies. Here, we used transcriptomics and proteomics for identifying molecular signatures of interference with thyroid hormone signaling preceding physiological effects in zebrafish embryos. For this, we analyzed the thyroid hormone 3,3',5-triiodothyronine (T3) and the thyroid peroxidase inhibitor 6-propyl-2-thiouracil (6-PTU) as model substances for increased and repressed thyroid hormone signaling in a modified zebrafish embryo toxicity test. We identified consistent gene expression fingerprints for both modes-of-action (MoA) at sublethal test concentrations. T3 and 6-PTU both significantly target the expression of genes involved in muscle contraction and functioning in an opposing fashion, allowing for a mechanistic refinement of key event relationships in thyroid-related adverse outcome pathways in fish. Furthermore, our fingerprints identify biomarker candidates for thyroid disruption hazard screening approaches. Perspectively, our findings will promote the AOP-based development of in vitro assays for thyroidal ED assessment, which in the long term will contribute to a reduction of regulatory animal tests.


Asunto(s)
Disruptores Endocrinos , Contaminantes Químicos del Agua , Animales , Biomarcadores , Embrión no Mamífero , Disruptores Endocrinos/toxicidad , Glándula Tiroides , Toxicogenética , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/genética
14.
Artículo en Inglés | MEDLINE | ID: mdl-33269444

RESUMEN

In situ burning (ISB) is discussed to be one of the most suitable response strategies to combat oil spills in extreme conditions. After burning, a highly viscous and sticky residue is left and may over time pose a risk of exposing aquatic biota to toxic oil compounds. Scientific information about the impact of burn residues on the environment is scarce. In this context, a comprehensive ISB field experiment with approx. 1000L IFO 180 was conducted in a fjord in Greenland. The present study investigated the toxicity of collected ISB residues to early life stages of zebrafish (Danio rerio) as a model for potentially exposed pelagic organisms. The toxicity of ISB residues on zebrafish embryos was compared with the toxicity of the initial (unweathered) IFO 180 and chemically dispersed IFO 180. Morphological malformations, hatching success, swimming behavior, and biomarkers for exposure (CYP1A activity, AChE inhibition) were evaluated in order to cover the toxic response on different biological organization levels. Across all endpoints, ISB residues did not induce greater toxicity in zebrafish embryos compared with the initial oil. The application of a chemical dispersant increased the acute toxicity most likely due to a higher bioavailability of dissolved and particulate oil components. The results provide insight into the adverse effects of ISB residues on sensitive life stages of fish in comparison with chemical dispersant application.

15.
Sci Total Environ ; : 143522, 2020 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-33246726

RESUMEN

Metabolism has to be considered during the toxicological assessment of chemical and environmental samples because it is an important process in the mammalian liver. It can be assessed in vitro via liver homogenates called S9-fractions, an external metabolic activation system. However, the external metabolic activation systems can vary greatly in their composition due to biological variations among individual animals and animal strains that the S9-fraction are derived as well as the differences in the production treatment. To gain more insight into these variances, three different but commonly used rat-derived S9-fractions were compared in the present study for their variance and performance with a reference compound in the Ames fluctuation assay with Salmonella typhimurium strains TA 98 and TA 100 according to ISO 11350. Severe shortcomings of conventional rat-derived S9-fractions were observed in the present study, such that S9-fractions differed significantly within the same rat strain and for different types of induction procedures in regards to the metabolic capability. An intrinsic mutagenic potential of the three rat-derived S9-fractions were identified in the Ames fluctuation assay with varying S9-fraction concentrations. To address some of the shortcomings of the animal-derived S9-fraction, the present study investigated the use and performance of a biotechnological, animal-free alternative, ewoS9R, in comparison to one of the rat-derived S9-fraction as the others showed a mutagenic potential themselves. Specifically, 12 different chemicals were used as a reference to determine if ewoS9R could serve as an adequate and more consistent replacement of traditional rat-derived metabolic activation systems: 8 pro-mutagenic compounds (i.e., require metabolic activation to show a mutagenic potential), one pro-mutagenic compound but not in the tested strains, one mutagenic compound without metabolic activation and two compounds that are equivocal in the literature. EwoS9R was evaluated as a promising approach in the Ames fluctuation assay with 5 compounds observed to have similar results with both rat-derived S9-fraction and ewoS9R (41%), for 3 compounds ewoS9R was a better metabolization system than the rat-derived S9-fraction (16%). Further research is necessary to determine the full potential of ewoS9R in comparison to rat-derived S9-fractions.

16.
Sci Total Environ ; : 143030, 2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33129534

RESUMEN

Bioanalytical equivalents (BEQs) of mixtures and environmental samples are widely used to reflect the potential threat of pollutants in the environment and can be obtained by bioassays or using chemical analysis combined with relative potencies (REPs). In this study, the relationships between bioassay-detected BEQs (Bio-BEQs) and chemically analyzed BEQs (Chem-BEQs) were studied. BEQs and REPs are correlated with effect level and the concentration-response curves of the reference standard and sample. Thus, effect level (e.g., EC10, EC25 and EC50) should be addressed for the BEQ values obtained from bioassays or chemical analyses. The previous prerequisites for REPs application (i.e., curves that are parallel and have the same maximum response) are redundant, and the use of REPs for the calculation of BEQs or in risk assessment should instead be based on the same effect level. For a complex mixture with many components, all active components can be regarded as dilutions of a standard compound for inducing a specific effect. Relative toxicity estimates based on EC50 ignore the contribution of weak-active components with maximum response below EC50 of the reference standard, especially in complex mixtures or environmental samples. REPs based on an effect level EC10 that can be clearly discriminated from background response are recommended for BEQ calculation. As an example, the aryl hydrocarbon receptor (AhR)-mediated activity of US EPA priority polycyclic aromatic hydrocarbons (PAHs) in RTL-W1 cells was used to assess the reliability of REPs for mixture toxicity prediction based on the effect level EC10.

17.
ALTEX ; 37(4): 693-708, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33080039

RESUMEN

In biological systems (cell culture media, cells, body fluids), drugs/toxicants are usually not freely dissolved but partially bound to biomolecules; only a fraction of the chemical is free/unbound (fu). To predict pharmacological effects and toxicity, it is important that the fu of the drug is known. As the differences between free and nominal concentrations are determined by test system parameters (e.g., the protein and lipid content, and the type of surface material), comparison of nominal concentrations between two different new approach methods (NAM) may lead to faulty conclusions. The same problem exists when in vitro concentrations are compared to those in human subjects. Therefore, the respective fu of a chemical in a test system needs to be determined for in vitro-to-in vivo extrapolations (IVIVE). Besides direct measurements, prediction models can help to obtain fu. Here we describe a simplified approach to approximate fu and provide background information on the underlying assumptions. Comparative predictions and measurements of fu of various drugs are shown to exemplify the approach. Basic input data, like protein and lipid concentrations, are also provided. Beyond such test systems data, the only required chemical-specific inputs are the lipophilicity of the candidate drug and its ionization state, as determined by the dissociation constants of its acidic or basic groups. This overview is intended to be used by any lab scientist without specific toxicokinetics training to obtain an estimate of fu in a given cell culture medium.

18.
Sci Total Environ ; 749: 141468, 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32827816

RESUMEN

Many environmental pollutants pose a toxicological hazard only after metabolic activation. In vitro bioassays using cell lines or bacteria have often no or reduced metabolic activity, which impedes their use in the risk assessment. To improve the predictive capability of in vitro assays, external metabolization systems like the liver S9 fraction are frequently combined with in vitro toxicity assays. While it is typical for S9 fractions that samples and testing systems are combined in the same exposure system, we propose to separate the metabolism step and toxicity measurement. This allows for a modular combination of metabolic activation by enzymes isolated from rat liver (S9) or a biotechnological alternative (ewoS9R) with in vitro bioassays that lack metabolic capacity. Benzo(a)pyrene and 2-aminoanthracene were used as model compounds to optimize the conditions for the S9 metabolic degradation/activation step. The Ames assay with Salmonella typhimurium strains TA98 and TA100 was applied to validate the set-up of decoupling the S9 activation/metabolism from the bioassay system. S9 protein concentration of 0.25 mgprotein/mL, a supplement of 0.13 mM NADPH and a pre-incubation time of 100 min are recommended for activation of samples prior to dosing them to in vitro bioassays using the regular dosing protocols of the respective bioassay. EwoS9R performed equally well as Moltox S9, which is a step forward in developing true animal-free in vitro bioassays. After pre-incubation with S9 fraction, chemicals induced bacteria revertants in both the TA98 and the TA100 assay as efficiently as the standard Ames assay. The pre-incubation of chemicals with S9 fraction could serve for a wide range of cellular in vitro assays to efficiently combine activation and toxicity measurement, which may greatly facilitate the application of these assays for chemical hazard assessment and monitoring of environmental samples.

19.
Aquat Toxicol ; 226: 105555, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32645607

RESUMEN

Fish strongly rely on olfaction as a variety of essential behaviors such as foraging and predator avoidance are mediated by the olfactory system. Cadmium (Cd) is known to impair olfaction and accumulate in the olfactory epithelium (OE) and bulb (OB) of fishes. In the present study, the acute toxicity of Cd on olfaction in zebrafish (Danio rerio) was characterized on the molecular and behavioral level. To this end, quantitative real-time PCR was performed in order to analyze the expression of selected genes in both the OE and OB. Moreover, the response of zebrafish to an alarm cue was investigated. Following 24 h of exposure to Cd, the expression of genes associated with olfactory sensory neurons was reduced in the OE. Furthermore, the antioxidant genes peroxiredoxin 1 (prdx1) and heme oxygenase 1 (hmox1), as well as the metallothionein 2 gene (mt2) were upregulated in the OE, whereas hmox1 and the stress-inducible heat shock protein 70 gene (hsp70) were upregulated in the OB upon exposure to Cd. Following stimulation with a conspecific skin extract, zebrafish displayed a considerable disruption of the antipredator behavior with increasing Cd concentration. Taken together, Cd impaired olfaction in zebrafish, thereby disrupting the antipredator response, which is crucial for the survival of individuals. Cellular stress followed by disruption of olfactory sensory neurons may have contributed to the observed behavioral deficits.


Asunto(s)
Conducta Animal/efectos de los fármacos , Cadmio/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Olfato/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Pez Cebra , Animales , Antioxidantes/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Metalotioneína/genética , Metalotioneína/metabolismo , Mucosa Olfatoria/efectos de los fármacos , Olfato/genética , Pez Cebra/genética , Pez Cebra/fisiología
20.
Toxics ; 8(2)2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32604793

RESUMEN

Genotoxicity assessment is of high relevance for crude and refined petroleum products, since oil compounds are known to cause DNA damage with severe consequences for aquatic biota as demonstrated in long-term monitoring studies. This study aimed at the optimization and evaluation of small-scale higher-throughput assays (Ames fluctuation, micronucleus, Nrf2-CALUX®) covering different mechanistic endpoints as first screening tools for genotoxicity assessment of oils. Cells were exposed to native and chemically dispersed water-accommodated fractions (WAFs) of three oil types varying in their processing degree. Independent of an exogenous metabolic activation system, WAF compounds induced neither base exchange nor frame shift mutations in bacterial strains. However, significantly increased chromosomal aberrations in zebrafish liver (ZF-L) cells were observed. Oxidative stress was indicated for some treatments and was not correlated with observed DNA damage. Application of a chemical dispersant increased the genotoxic potential rather by the increased bioavailability of dissolved and particulate oil compounds. Nonetheless, the dispersant induced a clear oxidative stress response, indicating a relevance for general toxic stress. Results showed that the combination of different in vitro assays is important for a reliable genotoxicity assessment. Especially, the ZF-L capable of active metabolism and DNA repair seems to be a promising model for WAF testing.

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