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Sökning: WFRF:(Engwall Magnus 1965 )

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1.
  • Alijagic, Andi, 1992-, et al. (författare)
  • A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
  • 2023
  • Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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2.
  • Alijagic, Andi, 1992-, et al. (författare)
  • Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
  • 2022
  • Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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3.
  • Nordén, Marcus, 1982-, et al. (författare)
  • Perfluorooctane sulfonate increases β-oxidation of palmitic acid in chicken liver
  • 2012
  • Ingår i: Environmental Science and Pollution Research. - Heidelberg, Germany : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 19:5, s. 1859-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Perfluorooctane sulfonate (PFOS) belongs to a group of chemicals called perfluoroalkyl acids that have been extensively used in various applications such as stain and oil resistant treatments for fabrics, fire-fighting foams, and insecticides. These chemicals present an environmental and health risk being present in many samples both in wildlife and humans. In this study, we investigate the effect of PFOS on fatty acid β-oxidation in developing chicken embryos.Methods: Fertilized chicken eggs were exposed in ovo to PFOS at day 4 of incubation. On day 10, the eggs were dissected and livers were incubated in vitro with (3)H-palmitic acid for 2 h. The media were collected, and after clean up, the amount of tritiated water was measured with liquid scintillation counting to determine the rate of palmitic acid β-oxidation.Results: PFOS was found to induce fatty acid β-oxidation at doses starting from a lowest observed effect level (LOEL) of 0.1 μg/g egg weight. Maximum induction of 77 % compared to control was seen at 0.3 μg/g.Conclusions: The administered doses in which effects are seen are around and even lower than the levels that can be found in wild populations of birds. General population human levels are a factor of two to three times lower than the LOEL value of this study. The environmental contamination of PFOS therefore presents a possibility of effects in wild populations of birds.
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4.
  • Schönlau, Christine, 1986- (författare)
  • Microplastics in the marine environment and the assessment of potential adverse effects of associated chemicals
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • During the last decade plastics have gained interest by scientists as emerging pollutants particularly in the marine environment due to their ubiquity and persistence. While several studies report the occurrence of microplastics in surface waters globally, there are no harmonized methods to sample and measure microplastics, and the knowledge of toxicological effects in the marine ecosystem is scarce. One of the concerns is that microplastics could transfer hazardous chemicals into organism upon ingestion.In this thesis chemical and bioanalytical methods were combined to address the hypothesis that plastic pollution poses a risk for marine ecosystems by exposure to plastic associated chemicals such as sorbed environmental pollutants, additives, and monomers. Six different pristine plastic polymers were studied which have been deployed in the marine and freshwater system for up to 12 months. Potential adverse effects of plastic associated chemicals were investigated with in vitro reporter gene assays which can be activated by several chemical classes. The main focus was on the aryl hydrocarbon receptor-mediated activity for the assessment of dioxin-like chemicals. Different groups of persistent environmental pollutants, which are present in the aquatic environment, were analyzed by gas chromatographic mass spectrometric methods. The contribution of the targeted chemicals to the measured biological activities was examined by conducting potency balance calculations. A better knowledge about the occurrence of microplastics in the waters surrounding Sweden was gained by sampling surface waters comparing two different sampling techniques, trawl and in-situ pump.The plastic pellets induced bioactivities in most tested reporter gene assays and the activities varied by type of polymer. In the majority of samples the contribution of the targeted environmental pollutants to the observed bioactivities was low. Concentrations of microplastics > 0.3 mm in surface waters around Sweden were observed to be low and the findings of this thesis suggest that the tested polymers with sizes 2-4 mm will not lead to an increased risk for marine ecosystems in terms of exposure to chemicals.
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5.
  • Alijagic, Andi, 1992-, et al. (författare)
  • Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
  • 2024
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 183
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.
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6.
  • Alijagic, Andi, 1992-, et al. (författare)
  • Metabolic and phenotypic changes induced by PFAS exposure in two human hepatocyte cell models
  • 2024
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 190
  • Tidskriftsartikel (refereegranskat)abstract
    • PFAS are ubiquitous industrial chemicals with known adverse health effects, particularly on the liver. The liver, being a vital metabolic organ, is susceptible to PFAS-induced metabolic dysregulation, leading to conditions such as hepatotoxicity and metabolic disturbances. In this study, we investigated the phenotypic and metabolic responses of PFAS exposure using two hepatocyte models, HepG2 (male cell line) and HepaRG (female cell line), aiming to define phenotypic alterations, and metabolic disturbances at the metabolite and pathway levels. The PFAS mixture composition was selected based on epidemiological data, covering a broad concentration spectrum observed in diverse human populations. Phenotypic profiling by Cell Painting assay disclosed predominant effects of PFAS exposure on mitochondrial structure and function in both cell models as well as effects on F-actin, Golgi apparatus, and plasma membrane-associated measures. We employed comprehensive metabolic characterization using liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). We observed dose-dependent changes in the metabolic profiles, particularly in lipid, steroid, amino acid and sugar and carbohydrate metabolism in both cells as well as in cell media, with HepaRG cell line showing a stronger metabolic response. In cells, most of the bile acids, acylcarnitines and free fatty acids showed downregulation, while medium-chain fatty acids and carnosine were upregulated, while the cell media showed different response especially in relation to the bile acids in HepaRG cell media. Importantly, we observed also nonmonotonic response for several phenotypic features and metabolites. On the pathway level, PFAS exposure was also associated with pathways indicating oxidative stress and inflammatory responses. Taken together, our findings on PFAS-induced phenotypic and metabolic disruptions in hepatocytes shed light on potential mechanisms contributing to the broader comprehension of PFAS-related health risks.
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7.
  • Alijagic, Andi, 1992-, et al. (författare)
  • NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity
  • 2023
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
  • Forskningsöversikt (refereegranskat)abstract
    • Micro- and nanoplastics (MNPs) are emerging pollutants with scarcely investigated effects on human innate immunity. If they follow a similar course of action as other, more thoroughly investigated particulates, MNPs may penetrate epithelial barriers, potentially triggering a cascade of signaling events leading to cell damage and inflammation. Inflammasomes are intracellular multiprotein complexes and stimulus-induced sensors critical for mounting inflammatory responses upon recognition of pathogen- or damage-associated molecular patterns. Among these, the NLRP3 inflammasome is the most studied in terms of activation via particulates. However, studies delineating the ability of MNPs to affect NLRP3 inflammasome activation are still rare. In this review, we address the issue of MNPs source and fate, highlight the main concepts of inflammasome activation via particulates, and explore recent advances in using inflammasome activation for assessment of MNP immunotoxicity. We also discuss the impact of co-exposure and MNP complex chemistry in potential inflammasome activation. Development of robust biological sensors is crucial in order to maximize global efforts to effectively address and mitigate risks that MNPs pose for human health.
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8.
  • Alijagic, Andi, 1992-, et al. (författare)
  • The triple exposure nexus of microplastic particles, plastic-associated chemicals, and environmental pollutants from a human health perspective
  • 2024
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 188
  • Forskningsöversikt (refereegranskat)abstract
    • The presence of microplastics (MPs) is increasing at a dramatic rate globally, posing risks for exposure and subsequent potential adverse effects on human health. Apart from being physical objects, MP particles contain thousands of plastic-associated chemicals (i.e., monomers, chemical additives, and non-intentionally added substances) captured within the polymer matrix. These chemicals are often migrating from MPs and can be found in various environmental matrices and human food chains; increasing the risks for exposure and health effects. In addition to the physical and chemical attributes of MPs, plastic surfaces effectively bind exogenous chemicals, including environmental pollutants (e.g., heavy metals, persistent organic pollutants). Therefore, MPs can act as vectors of environmental pollution across air, drinking water, and food, further amplifying health risks posed by MP exposure. Critically, fragmentation of plastics in the environment increases the risk for interactions with cells, increases the presence of available surfaces to leach plastic-associated chemicals, and adsorb and transfer environmental pollutants. Hence, this review proposes the so-called triple exposure nexus approach to comprehensively map existing knowledge on interconnected health effects of MP particles, plastic-associated chemicals, and environmental pollutants. Based on the available data, there is a large knowledge gap in regard to the interactions and cumulative health effects of the triple exposure nexus. Each component of the triple nexus is known to induce genotoxicity, inflammation, and endocrine disruption, but knowledge about long-term and inter-individual health effects is lacking. Furthermore, MPs are not readily excreted from organisms after ingestion and they have been found accumulated in human blood, cardiac tissue, placenta, etc. Even though the number of studies on MPs-associated health impacts is increasing rapidly, this review underscores that there is a pressing necessity to achieve an integrated assessment of MPs’ effects on human health in order to address existing and future knowledge gaps.
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9.
  • Behnisch, Peter, et al. (författare)
  • Results of an international interlaboratory study on dioxin-like activities in drinking-, river surface- and wastewater using DR CALUX bioassay
  • 2024
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 920
  • Tidskriftsartikel (refereegranskat)abstract
    • Aquatic animals and consumers of aquatic animals are exposed to increasingly complex mixtures of known and as-yet-unknown chemicals with dioxin-like toxicities in the water cycle. Effect- and cell-based bioanalysis can cover known and yet unknown dioxin and dioxin-like compounds as well as complex mixtures thereof but need to be standardized and integrated into international guidelines for environmental testing. In an international laboratory testing (ILT) following ISO/CD 24295 as standard procedure for rat cell-based DR CALUX un-spiked and spiked extracts of drinking-, surface-, and wastewater were validated to generate precision data for the development of the full ISO-standard. We found acceptable repeatability and reproducibility ranges below 36 % by DR CALUX bioassay for the tested un-spiked and spiked water of different origins. The presence of 17 PCDD/Fs and 12 dioxin-like PCBs was also confirmed by congener-specific GC-HRMS analysis. We compared the sum of dioxin-like activity levels measured by DR CALUX bioassay (expressed in 2,3,7,8-TCDD Bioanalytical Equivalents, BEQ; ISO 23196, 2022) with the obtained GC-HRMS chemical analysis results converted to toxic equivalents (TEQ; van den Berg et al., 2013).
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10.
  • Beiras, R., et al. (författare)
  • Ingestion and contact with polyethylene microplastics does not cause acute toxicity on marine zooplankton
  • 2018
  • Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 360, s. 452-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Toxicity of polyethylene microplastics (PE-MP) of size ranges similar to their natural food to zooplanktonic organisms representative of the main taxa present in marine plankton, including rotifers, copepods, bivalves, echinoderms and fish, was evaluated. Early life stages (ELS) were prioritized as testing models in order to maximize sensitivity. Treatments included particles spiked with benzophenone-3 (BP-3), a hydrophobic organic chemical used in cosmetics with direct input in coastal areas. Despite documented ingestion of both virgin and BP-3 spiked microplastics no acute toxicity was found at loads orders of magnitude above environmentally relevant concentrations on any of the invertebrate models. In fish tests some effects, including premature or reduced hatching, were observed after 12 d exposure at 10 mg L-1 of BP-3 spiked PE-MP. The results obtained do not support environmentally relevant risk of microplastics on marine zooplankton. Similar approaches testing more hydrophobic chemicals with higher acute toxicity are needed before these conclusions could be extended to other organic pollutants common in marine ecosystems. Therefore, the replacement of these polymers in consumer products must be carefully considered.
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11.
  • Brunström, Björn, et al. (författare)
  • EROD induction in cultured chick embryo liver : a sensitive bioassay for dioxin-like environmental pollutants
  • 1995
  • Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 14:5, s. 837-842
  • Tidskriftsartikel (refereegranskat)abstract
    • A technique for studying 7-ethoxyresorufin O-deethylase (EROD) induction in chick embryo liver in vitro was developed. Livers from 8-d-old embryos were cultured in rotating vials at 37 degrees C for 48 h in a medium to which DMSO-dissolved test compounds had been added. This bioassay proved to be highly sensitive to dioxin-like compounds, and its usefulness for assessing the toxic potency of such compounds in environmental samples was demonstrated. Concentration-response curves were determined for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-penlachlorobiphenyl (PCB IUPAC no. 126), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,3',4,4'-pentachlorobiphenyl (PCB 105), and benzo[k]fluoranthene (BkF). TCDD induced EROD in a concentration-dependent manner, having an EC50 of 5.0 x 10(-12) M. The cultured embryo livers were extremely sensitive to TCDD, and about 30 fg of this compound per liver (2 x 10(-13) M) was enough to significantly induce EROD. The EC50 values obtained for PCBs 126, 77, 105, and BkF were 4,4 x 10(-11) M, 9.2 x 10(-9) M, 1.6 x 10(-8) M, and 6.2 x 10(-7) M, respectively. The maximal induction levels obtained for three different preparations of polychlorinated naphthalenes (PCNs) were less than those of the other compounds tested. When the technical PCN mixture Halowax 1014 was coadministered with TCDD, the induction was lower than that caused by TCDD alone. An organic extract of fly ash from a municipal waste combustion plant was very potent. Considering its contents of polychlorinated dibenzo-p-dioxins/furans, expressed as TCDD equivalents, the EC50 obtained was close to that for TCDD.
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12.
  • Chavan, Swapnil, et al. (författare)
  • Predicting Chemical-Induced Liver Toxicity Using High-Content Imaging Phenotypes and Chemical Descriptors : A Random Forest Approach
  • 2020
  • Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 33:9, s. 2261-2275
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatotoxicity is a major reason for the withdrawal or discontinuation of drugs from clinical trials. Thus, better tools are needed to filter potential hepatotoxic drugs early in drug discovery. Our study demonstrates utilization of HCI phenotypes, chemical descriptors, and both combined (hybrid) descriptors to construct random forest classifiers (RFCs) for the prediction of hepatotoxicity. HCI data published by Broad Institute provided HCI phenotypes for about 30 000 samples in multiple replicates. Phenotypes belonging to 346 chemicals, which were tested in up to eight replicates, were chosen as a basis for our analysis. We then constructed individual RFC models for HCI phenotypes, chemical descriptors, and hybrid (chemical and HCI) descriptors. The model that was constructed using selective hybrid descriptors showed high predictive performance with 5-fold cross validation (CV) balanced accuracy (BA) at 0.71, whereas within the given applicability domain (AD), independent test set and external test set prediction BAs were equal to 0.61 and 0.60, respectively. The model constructed using chemical descriptors showed a similar predictive performance with a 5-fold CV BA equal to 0.66, a test set prediction BA within the AD equal to 0.56, and an external test set prediction BA within the AD equal to 0.50. In conclusion, the hybrid and chemical descriptor-based models presented here should be considered as a new tool for filtering hepatotoxic molecules during compound prioritization in drug discovery.
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13.
  • Dulio, Valeria, et al. (författare)
  • The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate!
  • 2020
  • Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken.
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14.
  • Eichbaum, Kathrin, et al. (författare)
  • In vitro bioassays for detecting dioxin-like activity : Application potentials and limits of detection, a review
  • 2014
  • Ingår i: Science of the Total Environment. - Amsterdam : Elsevier. - 0048-9697 .- 1879-1026. ; 487, s. 37-48
  • Tidskriftsartikel (refereegranskat)abstract
    • Use of in vitro assays as screening tool to characterize contamination of a variety of environmental matrices has become an increasingly popular and powerful toolbox in the field of environmental toxicology.While bioassays cannot entirely substitute analytical methods such as gas chromatography-mass spectrometry (GC-MS), the increasing improvement of cell lines and standardization of bioassay procedures enhance their utility as bioanalytical pre-screening tests prior to more targeted chemical analytical investigations. Dioxin-receptor-based assays provide a holistic characterization of exposure to dioxin-like compounds (DLCs) by integrating their overall toxic potential, including potentials of unknown DLCs not detectable via e.g. GC-MS. Hence, they provide important additional information with respect to environmental risk assessment of DLCs.This review summarizes different in vitro bioassay applications for detection of DLCs and considers the comparability of bioassay and chemical analytically derived toxicity equivalents (TEQs) of different approaches and various matrices. These range from complex samples such as sediments through single reference to compound mixtures. A summary of bioassay derived detection limits (LODs) showed a number of current bioassays to be equally sensitive as chemical methodologies, but moreover revealed that most of the bioanalytical studies conducted to date did not report their LODs, which represents a limitation with regard to low potency samples.
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15.
  • Eichbaum, Kathrin, et al. (författare)
  • The dioRAMA project : assessment of dioxin-like activity in sediments and fish (Rutilus rutilus) in support of the ecotoxicological characterization of sediments
  • 2013
  • Ingår i: Journal of Soils and Sediments. - : Springer. - 1439-0108 .- 1614-7480. ; 13:4, s. 770-774
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Given the complex interactions of re-suspension processes and bioavailability of sediment-bound pollutants such as dioxin-like chemicals, there is need for a better integrative understanding of the cause-effect relationship of these pollutants. Currently, the majority of studies investigating potential risks of these chemicals only focus on characterizing sediment extracts via in vitro bioassays, thereby disregarding bioavailability, uptake, metabolism, and elimination rates of these compounds in vivo. To determine to which extent mechanism-specific effects in vitro reflect possible adverse effects in vivo, the research project dioRAMA, involving partnership between the Institute for Environmental Research of RWTH Aachen University and the Department Biochemistry/Ecotoxicology of the German Federal Institute of Hydrology, was established.Methods: Animals from an elevated trophic level-common roach (Rutilus rutilus)-will be exposed to sediments from two major German rivers. Exposure will be performed in a system that enables a concurrent monitoring of environmental parameters. In parallel, in vitro studies will be conducted to determine dioxin-like potentials of sediment and fish extracts from the in vivo exposure experiments using different cell lines with varying endpoints. Moreover, extract fractionation procedures, using the strategy of effect-directed analysis, will enable the detection of specific contaminant groups responsible for the biological activity observed.Conclusion: A closer interconnection between applied ecotoxicological science and regulatory needs will facilitate the improved assessment of dioxin-like compounds in sediment and biota. Consequently, this will enable their application in sediment management programs, which is one of the main goals of the dioRAMA project.
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16.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Biological and chemical determination of contaminant levels in settling particulate matter and sediments : a Swedish river system before, during, and after dredging of PCB-contaminated lake sediments
  • 1998
  • Ingår i: Ambio. - 0044-7447 .- 1654-7209. ; 27:5, s. 403-410
  • Tidskriftsartikel (refereegranskat)abstract
    • A sensitive bioassay, based on EROD induction in cultured chicken embryo livers, was used together with chemical analysis to determine levels of dioxin-like contaminants in particulate matter in Eman. Extracts of sediment and settling particulate matter (SPM) collected in the river system before, during, and after dredging of a PCB contaminated lake, Lake Jarnsjon, were separated into three fractions containing a) monoaromatic/aliphatic; b) diaromatic (e.g., PCBs and polychlorinated dibenzodioxins and dibenzofurans); and c) polyaromatic compounds (e.g., polycyclic aromatic hydrocarbons). The samples from Lake Jarnsjon contained the highest PCB concentrations and the diaromatic extracts from Lake Jarnsjon samples showed the highest activities of EROD-inducing diaromatic compounds. The dioxin-like activity of the diaromatic fraction in sediment collected after the dredging of Jarnsjon had only around 1% of the activity of the pre-dredging sediment, showing that the remediation was successful in terms of removal of the PCB-contaminated sediment from the lake. In SPM collected immediately downstream from Jarnsjon, levels of diaromatic dioxin-like compounds were elevated during the dredging, and decreased after that. The post-dredging concentrations were however higher than in SPM from lakes upstream of Jarnsjon, showing that elevated levels of dioxin-like diaromatic compounds were still present in the water System downstream of Jarnsjon a couple of years after the dredging.
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17.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Cytochrome P450IA induction by a coplanar PCB, a PAH mixture, and PCB-contaminated sediment extracts following microinjection of rainbow trout sac-fry
  • 1994
  • Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X .- 1879-1514. ; 30:4, s. 311-324
  • Tidskriftsartikel (refereegranskat)abstract
    • The 7-ethoxyresorufin-O-deethylase (EROD)-inducing potencies of a coplanar polychlorinated biphenyl (PCB) (3,3',4,3',5-pentachlorobiphenyl, IUPAC No. 126), a mixture of five polycyclic aromatic hydrocarbons (benzo(k)fluoranthene, benz(a)anthracene, benzo(a)pyrene, indeno(1,2,3-cd)pyrene and chrysene), and lipophilic compounds extracted from the sediments in a PCB-contaminated lake and from sediments in lakes up- and downstream, were studied in rainbow trout sac-fry in a 43-day study. The compounds/extracts were injected into the yolk sacs of newly hatched sac-fry and hepatic EROD activities and mortality rates were measured at various times after the injections. Five livers from each group were also examined by transmission electron microscopy. All the compounds/extracts induced hepatic EROD activities in the sac-fry. Ten days after injection the EROD activity caused by PCB No. 126 (1.3 ng per embryo) was 40-fold compared to the control activity. This was the highest induction rate observed in the experiment. For the sediment extracts, the highest induction rates were observed at the first sampling occasion, which for these groups was on day 24. The extract from the Lake Jarnsjon sediment was more potent as an EROD inducer than the extracts of sediments from the lakes up- and downstream from Lake Jarnsjon. None of the sediment extracts caused any significant mortality. In sac-fry injected with the PAH mixture, EROD was only slightly induced. The highest dose of PAHs (10 mu g per embryo) caused about 90% mortality by 24 days after injection. When the livers were examined by transmission electron microscopy, morphological alterations (e.g. hepatocyte degeneration and hypertrophy) were seen in the groups injected with Lake Jarnsjon sediment extract, PCB No. 126 and the highest dose of the PAH mixture (10 mu g per embryo).
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18.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Dioxin-like compounds in HPLC-fractionated extracts of marine samples from the east and west coast of Sweden : bioassay- and instrumentally-derived TCDD equivalents
  • 1997
  • Ingår i: Marine Pollution Bulletin. - 0025-326X .- 1879-3363. ; 34:12, s. 1032-1040
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipophilic extracts of sediment, settling particulate matter (SPM) and blue mussel (Mytilus edulis) samples, collected at coastal locations on the east and west coast of Sweden, were HPLC-separated into three fractions containing 1. monoaromatic/aliphatic, 2. diaromatic (e,g, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins and polychlorinated dibenzofuraus (PCDDs/Fs)), and 3, polyaromatic compounds (e,g, polycyclic aromatic hydrocarbons (PAHs)), The fractions were tested for dioxin-like effects using a sensitive bioassay, based on EROD-induction in cultured chicken embryo livers, The concentrations of PCDDs/Fs, PCBs and 15 PAHs in the samples were also determined, The polyaromatic fractions of the sediment samples were more potent as EROD-inducers than the diaromatic fractions, Only a small part of the EROD-induction caused by the polyaromatic fractions could be explained by the analysed PAHs in the samples, indicating presence of non-quantified polyaromatic EROD-inducing compounds in the samples, A greater pollution by EROD-inducing diaromatic and polyaromatic compounds on the east coast site than on the west coast site was seen, The filtration activities and faeces production of the mussels on the east coast experimental site increased the sedimentation of PCDDs/Fs, PCBs and PAHs, The described bioassay proved very useful in the assessment of dioxin-like compounds in both abiotic and biotic samples from the marine environment,
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19.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH)-inducing potency and lethality of chlorinated naphthalenes in chicken (Gallus domesticus) and eider duck (Somateria mollissima) embryos
  • 1994
  • Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 68:1, s. 37-42
  • Tidskriftsartikel (refereegranskat)abstract
    • The 7-ethoxyresorufin O-deethylase (EROD)- and aryl hydrocarbon hydroxylase (AHH)-inducing potencies and lethalities of a technical preparation of polychlorinated naphthalenes (PCNs) (Halowax 1014, approx imate congener ratio: 20% tetrachloronaphthalenes, 40% pentachloronaphthalenes, 40% hexachloronaphthalenes), a mixture of 50% 1,2,3,5,6,7-hexachloronaphthalene and 50% 1,2,3,4,6,7-hexachloronaphthalene (HxCN-mix), and 1,2,3,4,5,6,7-heptachloronaphthalene (HpCN) were studied in chicken (Gallus domesticus) and elder duck (Somateria mollissima) embryos. Mortality and hepatic EROD activity were determined on day 10 of incubation in chicken embryos exposed to various doses of the PCNs via the air-sacs of the eggs on day 7. The HxCN-mix and Halowax 1014 proved to have both embryolethal and EROD-inducing properties, while the HpCN had low EROD-inducing potency and embryolethality. ED(50) values for EROD induction by the HxCN-mix and Halowax 1014 were estimated to be 0.06 mg/kg egg and 0.2 mg/kg egg, respectively. Fifty percent of the chicken embryos died (6/12) when given 3.0 mg/kg of the HxCN-mix while a similar dose of Halowax 1014 caused mortality in 4 out of 12 chicken embryos. The dose-response curve for EROD induction by Halowax 1014 exhibited a decline after the maximal level was reached. When Halowax 1014 (1.0 mg/kg, egg) was coinjected with 3,3',4,4',5-pentachlorobiphenyl (PCB IUPAC #126) (0.1 mu g/kg egg) no additive effects on EROD activity were found, but when the same dose of Halowax 1014 was coinjected with a dose of PCB #126, known to cause maximal induction (1.0 mu g/kg egg), the resulting EROD activity was lower than that caused solely by 1.0 mu g PCB #126/kg egg. These findings indicate that Halowax 1014 has both EROD-inducing and EROD-inhibiting properties. Mortality and EROD and AHH activities were determined on day 18 (chicken) or day 24 (elder) of incubation in embryos exposed to 1.0 mg/kg egg via the yolk-sac on day 4 (chicken) or day 5 (elder). The HxCN-mix and Halowax 1014 induced AHH and EROD in both chicken and elder, but the induction rates were higher in the elder embryos. The HxCN-mix and Halowax 1014 caused degenerative hepatic lesions and pericardial oedema in the chicken embryos but not in the elder embryos. The most toxic PCNs tested (the HxCN-mix and Halowax 1014) were approximately of the same EROD-inducing potency as previously found for the most toxic mono-ortho-chlorinated biphenyls (Brunstrom 1990), and 1000 times less toxic and potent as EROD inducers compared with PCB #126 (Brunstrom and Andersson 1988). HpCN was considerably less toxic and exhibited a low EROD-inducing potency. The chicken embryos were more sensitive to the hepatotoxic effects produced by Halowax 1014 and the HxCN-mix than the elder duck embryos, while the elder embryos were more responsive in terms of EROD and AHH induction. The two HxCNs studied usually make up approximately 1% of the total quantity of PCNs present in Halowax 1014 [when determined with gas chromatography (flame ionization detection)]. Therefore, the relatively high toxic potency of Halowax 1014 cannot be explained by its content of the two HxCNs.
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20.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Fate of Ah-receptor agonists in organic household waste during anaerobic degradation : estimation of levels using EROD induction in organ cultures of chick embryo livers
  • 2002
  • Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 297:1-3, s. 105-108
  • Tidskriftsartikel (refereegranskat)abstract
    • The fate of 7-ethoxyresorufin O-deethylase (EROD)-inducing compounds in source-separated organic household waste subject to anaerobic degradation (i.e. mesophilic/thermophilic anaerobic treatment) was investigated using organ cultures of embryonic chicken livers from fertilised hen eggs. This bioassay reflects the combined effect of all EROD-inducing, possibly dioxin-like compounds in a sample, including chemicals that are seldom or never analysed. All samples tested induced EROD in the bioassay, indicating the presence of dioxin-like compounds. In the anaerobic processes, the amounts of acid-resistant EROD-inducing compounds coming out of the reactors were considerably higher than the incoming amounts, especially for the low-temperature (mesophilic) process. This apparent production of EROD-inducing compounds may be due to de novo synthesis or to an increase in the EROD-inducing potency of the compounds in the material.
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21.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Levels of dioxin-like compounds in sewage sludge determined with a bioassay based on EROD induction in chicken embryo liver cultures
  • 1999
  • Ingår i: Chemosphere. - 0045-6535 .- 1879-1298. ; 38:10, s. 2327-2343
  • Tidskriftsartikel (refereegranskat)abstract
    • A bioassay for the detection of dioxin-like compounds was used to estimate levels in sewage sludge from Swedish sewage treatment plants (STPs). The sludge extracts were HPLC-separated into three fractions containing a) monoaromatic/aliphatic, b) diaromatic (e.g. polychlorinated biphenyls [PCBs], polychlorinated dibenzodioxins and polychlorinated dibenzofurans [PCDDs/Fs]), and c) polyaromatic compounds (e.g. polycyclic aromatic hydrocarbons [PAHs]). The bioassay, which is based on EROD (7-ethoxyresorufin O-deethylase) induction in cultured chicken embryo livers detected dioxin-like activity in all unfractionated extracts and in the di- and polyaromatic fractions of all sludge extracts, but not in the monoatomatic/aliphatic fractions. The levels ranged between 6 and 109 pg bio-TEQ/g sludge (d.w.). In sediment samples from rural lakes in Sweden, levels of about 5 pg bio-TEQ/g (d.w.) have been found. The polyaromatic fractions of the sludge samples were potent in the bioassay, probably due to various PAHs and other polyaromatics in the sludge. The levels of six PAHs that are screened for in the sludge at Swedish STPs accounted for only 3-10% of the observed EROD-induction by the polyaromatic fractions. Consequently, many other polyaromatic EROD-inducing compounds were present in the sludge. Inclusion of a biological test like the chicken embryo liver bioassay in the screening of sludge would improve the ability to detect the presence of bioactive dioxin-like compounds. A theoretical estimation of bio-TEQ concentrations in farm-soil following long-term application of sludge with bio-TEQ concentrations similar to those observed in this investigation indicated that the bio-TEQ levels in soil would increase very slowly over time. The chicken embryo liver bioassay proved useful in assessing levels of dioxin-like compounds in sewage sludge and it gives valuable complementary information to chemical analysis data.
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22.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Polycyclic aromatic hydrocarbons (PAHs) reduce hepatic beta-oxidation of fatty acids in chick embryos
  • 2013
  • Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 20:3, s. 1881-1888
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycyclic aromatic hydrocarbons (PAHs) are widespread fused-ring contaminants formed during incomplete combustion of almost all kind of organic materials from both natural and anthropogenic sources. Some PAHs have been shown to be carcinogenic to humans, and a wide range of PAHs are found in wildlife all around the globe including avian species. The purpose of this project was to assess the effects of a standard mixture of 16 PAHs (United States Environmental Protection Agency) on the hepatic fatty acid beta-oxidation in chicken embryos (Gallus gallus domesticus) exposed in ovo. The hepatic beta-oxidation was measured using a tritium release assay with [9,10-H-3]-palmitic acid (16:0) as substrate. Treated groups were divided into groups of 0.05, 0.1, 0.3, 0.5, and 0.8 mg PAHs/kg egg weight. The hepatic beta-oxidation was reduced after exposure in ovo to the 16 PAHs mixture compared to control. The mechanisms causing reduced fatty acid oxidation in the present study are unclear, however may be due to deficient membrane structure, the functionality of enzymes controlling the rate of fatty acid entering into the mitochondria, or complex pathways connected to endocrine disruption. To the best of our knowledge, this is the first time a PAH-caused reduction of hepatic beta-oxidation of fatty acids in avian embryos has been observed. The implication of this finding on risk assessment of PAH exposure in avian wildlife remains to be determined.
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23.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Toxic potencies of extracts of sediment and settling particulate matter collected in the recipient of a bleached pulp mill effluent before and after abandoning chlorine bleaching
  • 1997
  • Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 16:6, s. 1187-1194
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracts of bottom sediment and settling particulate matter (SPM) samples collected in the recipient water body of a bleached pulp mill effluent were separated into three fractions: monoaromatic/aliphatic compounds, diaromatic compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans), and polyaromatic compounds assessment of dioxinlike potency were an in vitro assay, based on the induction of 7-ethoxyresorufin-O-deethylase (EROD) in chicken embryo livers, a test for EROD induction in ovo using chicken embryos, and an immunotoxicity test measuring inhibition of lymphoid cell development in cultured fetal mouse thymuses. The samples collected closest to the mill were the most potent. There was a time-dependent decrease in dioxinlike potency in the SPM samples collected near the mill, which coincided with the cessation of chlorine gas bleaching at the mill. The bioassays in general, and the in vitro chicken embryo liver bioassay in particular, proved useful in the assessment of dioxinlike compounds in the sediment and SPM samples. The polyaromatic fractions of the samples were generally more potent than the diaromatic fractions. Only a small part of the effects caused by the polyaromatic fractions could be explained by 15 analyzed PAHs, indicating the presence of unquantified polyaromatic compounds with dioxinlike effects. This investigation indicates that the cessation of chlorine bleaching in the pulp mill resulted in a reduced load of diaromatic dioxinlike compounds in the recipient water body.
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24.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Toxic potencies of lipophilic extracts from sediments and settling particulate matter (SPM) collected in a PCB-contaminated river system
  • 1996
  • Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 15:2, s. 213-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Sediments and settling particulate matter (SPM) were sampled in a polychlorinated biphenyl (PCB)-contaminated lake, Lake Jarnsjon, and in lakes located up-/and downstream from Lake Jarnsjon. The 7-ethoxyresorufin O-deethylase (EROD)-inducing potencies of lipophilic extracts from sediment and SPM were investigated in organ cultures of chicken embryo livers (denoted in vitro chicken embryo liver bioassay). The extract from sediments collected in Lake Jarnsjon had the greatest EROD-inducing potency of the extracts studied, and it also contained the highest concentrations of PCBs, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated dibenzodioxins/furans (PCDDs/Fs). The non-ortho-chlorinated PCBs in the extracts were probably major contributors to the EROD induction noted. The EROD-inducing potency of sediment extract from the lake downstream Lake Jarnsjon was higher than that of extract from the upstream lake. This indicates that EROD-inducing substances were transported from Lake Jarnsjon sediment to the lake downstream. The extracts from Lake Jarnsjon sediment and SPM were separated into three fractions containing aliphatic/monoaromatic, diaromatic, and polyaromatic compounds, respectively, which were tested in the in vitro chicken embryo Liver bioassay. In all extracts, the aliphatic/monoaromatic fractions were low in EROD-inducing potency, while the polyaromatic fractions from SPM were more potent than their corresponding diaromatic fractions, indicating that they contained high concentrations of aromatic hydrocarbon (Ah) receptor ligands. Only a small part of the EROD induction caused by the polyaromatic fractions could be attributed to the 15 analyzed PAHs in the samples. The EROD-inducing potencies of the diaromatic fractions correlated quite well with their concentrations of PCDDs/Fs and PCBs. The in vitro chicken embryo liver bioassay detected low concentrations of EROD inducers in the extracts and therefore proved useful for estimating the contents of Ah receptor ligands in environmental samples.
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25.
  • Engwall, Magnus, 1965-, et al. (författare)
  • Uptake of dioxin-like compounds from sewage sludge into various plant species : assessment of levels using a sensitive bioassay
  • 2000
  • Ingår i: Chemosphere. - 0045-6535 .- 1879-1298. ; 40:9-11, s. 1189-1195
  • Tidskriftsartikel (refereegranskat)abstract
    • A bioassay for the detection of dioxin-like compounds was used to estimate uptake of dioxin-like compounds in carrots, oil seed rape seeds, zucchinis and cucumbers grown in soil amended with sewage sludge from Swedish sewage treatment plants (STP), This sensitive bioassay is based on 7-ethoxyresorufin O-deethylase (EROD)-induction in cultured chicken embryo livers and reflects the combined biological effect of all dioxin-like compounds in a sample, including ones that seldom are analyzed. The bioassay detected low concentrations of dioxin-like compounds in all carrot, zucchini and cucumber samples, but did not detect any dioxin-like compounds in the rape seeds. In carrots the concentrations were increased up to seven times when grown in soil amended with high applications of some of the sludge samples, while others did not increase the concentrations compared to control. More realistic sludge applications only increased the concentrations slightly. The sludge-fertilized carrots contained the highest concentrations of the investigated plants (up to 14 pg bioassay-derived TCDD equivalents (bio-TEQs)/g d.w.). In the carrots, differences in uptake of dioxin-like compounds depended on the sludge origin, which may be due to more easily bioaccumulated dioxin-like compounds in some sludge samples, or other components that facilitated uptake into the carrots. In the cucumbers, a more than two-fold increase (from 0.2 to 0.5 pg bio-TEQs/g d.w.) was observed in specimens grown in sludge-amended soil when compared to controls, suggesting a small uptake from the roots to the shoots. No sludge-dependent increase in uptake was seen in the zucchini fruits. The bio-TEQ levels were generally low in the consumable above ground plant parts of the investigated species. However, the question if repeated sludge application results in a soil accumulation of dioxin-like compounds, thereby increasing the risk of plant uptake, remains to be investigated.
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26.
  • Eriksson, Ulrika, 1972-, et al. (författare)
  • Examination of aryl hydrocarbon receptor (AhR), estrogenic and anti-androgenic activities, and levels of polyaromatic compounds (PACs) in tire granulates using in vitro bioassays and chemical analysis
  • 2022
  • Ingår i: Chemosphere. - : Pergamon Press. - 0045-6535 .- 1879-1298. ; 298
  • Tidskriftsartikel (refereegranskat)abstract
    • Tire granulates recovered from end-of-life tires contain a complex mixture of chemicals, amongst them polyaromatic compounds (PACs), of which many are recognized to be toxic and persistent in the environment. Only a few of these PACs are regularly monitored. In this study a combined approach of chemical analysis and a battery of CALUX® in vitro bioassays was used to determine PAC concentrations and estrogenic, (anti)-androgenic and aryl hydrocarbon receptor (AhR) activities in tire granulates. Tire granulates from a recycling company was analyzed for PAHs, alkyl-PAHs, oxy-PAHs and heterocyclic PACs (NSO-PACs), in total 85 PACs. The concentrations of PACs were between 42 and 144 mg/kg, with major contribution from PAHs (74-88%) followed by alkyl-PAHs (6.6-20%) and NSO-PACs (1.8-7.0%). The sum of eight priority PAHs were between 2.3 and 8.6 mg/kg, contributing with 4.7-8.2% of ∑PACs. Bioassay analysis showed presence of AhR agonists, estrogen receptor (ERα) agonists, and androgen receptor (AR) antagonists in the tire granulate samples. Only 0.8-2.4% of AhR-mediated activities could be explained by the chemical analysis. Benzo[k+j]fluoranthenes, benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene, 2-methylchrysene, and 3-methylchrysene were the major contributors to the AhR-mediated activities. The high contribution (98-99%) of unknown bioactive compounds to the bioassay effects in this study raises concerns and urges for further investigations of toxicants identification and source apportionment.
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27.
  • Fallet, Manon, 1992-, et al. (författare)
  • Present and future challenges for the investigation of transgenerational epigenetic inheritance
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 172
  • Forskningsöversikt (refereegranskat)abstract
    • Epigenetic pathways are essential in different biological processes and in phenotype-environment interactions in response to different stressors and they can induce phenotypic plasticity. They encompass several processes that are mitotically and, in some cases, meiotically heritable, so they can be transferred to subsequent generations via the germline. Transgenerational Epigenetic Inheritance (TEI) describes the phenomenon that phenotypic traits, such as changes in fertility, metabolic function, or behavior, induced by environmental factors (e.g., parental care, pathogens, pollutants, climate change), can be transferred to offspring generations via epigenetic mecha-nisms. Investigations on TEI contribute to deciphering the role of epigenetic mechanisms in adaptation, adver-sity, and evolution. However, molecular mechanisms underlying the transmission of epigenetic changes between generations, and the downstream chain of events leading to persistent phenotypic changes, remain unclear. Therefore, inter-, (transmission of information between parental and offspring generation via direct exposure) and transgenerational (transmission of information through several generations with disappearance of the triggering factor) consequences of epigenetic modifications remain major issues in the field of modern biology.In this article, we review and describe the major gaps and issues still encountered in the TEI field: the general challenges faced in epigenetic research; deciphering the key epigenetic mechanisms in inheritance processes; identifying the relevant drivers for TEI and implement a collaborative and multi-disciplinary approach to study TEI. Finally, we provide suggestions on how to overcome these challenges and ultimately be able to identify the specific contribution of epigenetics in transgenerational inheritance and use the correct tools for environmental science investigation and biomarkers identification.
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28.
  • Geng, Dawei, 1986-, et al. (författare)
  • Effect of perfluorooctanesulfonic acid (PFOS) on the liver lipid metabolism of the developing chicken embryo
  • 2019
  • Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier. - 0147-6513 .- 1090-2414. ; 170, s. 691-698
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorooctanesulfonate (PFOS) is a well-known contaminant in the environment and it has shown to disrupt multiple biological pathways, particularly those related with lipid metabolism. In this study, we have studied the impact of in ovo exposure to PFOS on lipid metabolism in livers in developing chicken embryos using lipidomics for detailed characterization of the liver lipidome. We used an avian model (Gallus gallus domesticus) for in ovo treatment at two levels of PFOS. The lipid profile of the liver of the embryo was investigated by ultra-high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry and by gas chromatography mass spectrometry. Over 170 lipids were identified, covering phospholipids, ceramides, di- and triacylglycerols, cholesterol esters and fatty acid composition of the lipids. The PFOS exposure caused dose dependent changes in the lipid levels, which included upregulation of specific phospholipids associated with the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, triacylglycerols with low carbon number and double bond count as well as of lipotoxic ceramides and diacylglycerols. Our data suggest that at lower levels of exposure, mitochondrial fatty acid β-oxidation is suppressed while the peroxisomal fatty acid β -oxidation is increased. At higher doses, however, both β -oxidation pathways are upregulated.
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29.
  • Gustavsson, L., et al. (författare)
  • Treatment of sludge containing nitro-aromatic compounds in reed-bed mesocosms : Water, BOD, carbon and nutrient removal
  • 2012
  • Ingår i: Waste Management. - : Elsevier. - 0956-053X .- 1879-2456. ; 32:1, s. 104-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the mid-1970s, Sweden has been depositing 1 million ton d.w sludge/year, produced at waste water treatment plants. Due to recent legislation this practice is no longer a viable method of waste management. It is necessary to improve existing and develop new sludge management techniques and one promising alternative is the dewatering and treatment of sludge in constructed wetlands. The aim of this study was to follow reduction of organic carbon, BOD and nutrients in an industrial sludge containing nitro-aromatic compounds passing through constructed small-scale wetlands, and to investigate any toxic effect such as growth inhibition of the common reed Phragmites australis. The result showed high reduction of all tested parameters in all the outgoing water samples, which shows that constructed wetlands are suitable for carbon and nutrient removal. The results also showed that P. australis is tolerant to xenobiotics and did not appear to be affected by the toxic compounds in the sludge. The sludge residual on the top of the beds contained low levels of organic carbon and is considered non-organic and could therefore be landfilled. Using this type of secondary treatment method, the amount of sludge could be reduced by 50-70%, mainly by dewatering and biodegradation of organic compounds.
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30.
  • Hafner, Christoph, et al. (författare)
  • Investigations on sediment toxicity of German rivers applying a standardized bioassay battery
  • 2015
  • Ingår i: Environmental Science and Pollution Research. - : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 22:21, s. 16358-16370
  • Tidskriftsartikel (refereegranskat)abstract
    • River sediments may contain a huge variety of environmental contaminants and play a key role in the ecological status of aquatic ecosystems. Contaminants adsorbed to sediments and suspended solids may contribute directly or after remobilization to an adverse ecological and chemical status of surface water. In this subproject of the joint research project DanTox, acetonic Soxhlet extracts from three German river sediments from the River Rhine (Altrip and Ehrenbreitstein with moderate contamination) and River Elbe (Veringkanal Hamburg heavily contaminated) were prepared and redissolved in dimethyl sulfoxide (DMSO). These extracts were analyzed with a standard bioassay battery with organisms from different trophic levels (bacteria, algae, Daphnia, fish) as well as in the Ames test and the umuC test for bacterial mutagenicity and genotoxicity according to the respective OECD and ISO guidelines. In total, 0.01 % (standard) up to 0.25 % (only fish embryo test) of the DMSO sediment extract was dosed to the test systems resulting in maximum sediment equivalent concentrations (SEQ) of 2 up to 50 g l(-1). The sediment of Veringkanal near Hamburg harbor was significantly more toxic in most tests compared to the sediment extracts from Altrip and Ehrenbreitstein from the River Rhine. The most toxic effect found for Veringkanal was in the algae test with an ErC50 (72 h) of 0.00226 g l(-1) SEQ. Ehrenbreitstein and Altrip samples were about factor 1,000 less toxic. In the Daphnia, Lemna, and acute fish toxicity tests, no toxicity at all was found at 2 g l(-1) SEQ. corresponding to 0.01 % DMSO. Only when increasing the DMSO concentration the fish embryo test showed a 22-fold higher toxicity for Veringkanal than for Ehrenbreitstein and Altrip samples, while the toxicity difference was less evident for the Daphnia test due to the overlaying solvent toxicity above 0.05 % dimethyl sulfoxide (DMSO). The higher toxicities observed with the Veringkanal sample are supported by the PAH and PCB concentrations analyzed in the sediments. The sediment extracts of Altrip andVeringkanal were mutagenic in the Ames tester strain TA98 with metabolic activation (S9mix). The findings allow a better ecotoxicological characterization of the sediments extensively analyzed in all subprojects of the DanTox project (e. g., Garcia-Kaeufer et al. Environ Sci Pollut Res. doi: 10.1007/s11356-014-3894-4, 2014; Schiwy et al. Environ Sci Pollut Res. doi: 10.1007/s11356-014-31850, 2014; Hollert and Keiter 2015). In the absence of agreed limit values for sediment extracts in standard tests, further data with unpolluted reference sediments are required for a quantitative risk assessment of the investigated polluted sediments.
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31.
  • Henriksson, Sara, 1975-, et al. (författare)
  • Uptake and bioaccumulation of PCDD/Fs in earthworms after in situ and in vitro exposure to soil from a contaminated sawmill site
  • 2017
  • Ingår i: Science of the Total Environment. - Amsterdam, Netherlands : Elsevier. - 0048-9697 .- 1879-1026. ; 580, s. 564-571
  • Tidskriftsartikel (refereegranskat)abstract
    • Uptake of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) was studied in earthworms collected from a sawmill site in Sweden with severe PCDD/Fs contamination (the hot spot concentration was 690,000 ng TEQWHO2005/kg d.w.) in order to investigate the transfer of PCDD/Fs from the site to the biota. PCDD/Fs concentrations in the collected earthworms were compared to PCDD/Fs concentrations in laboratory exposed earthworms (Eisenia fetida), which were exposed to contaminated soils from the sawmill site for 34 days. All analyses were performed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). PCDD/Fs concentrations in the earthworms ranged from 290 to 520,000 pg/g (f.w.). The main congeners found in both soils and earthworms were OCDF, 1234678-HpCDF, OCDD and 1234678-HpCDD. The study showed that the PCDD/Fs in the soil were biovailable to the earthworms and the PCDD/Fs concentrations in the soils correlated with the concentrations in the earthworms. Earthworm samples from soil with lower concentration had higher bioaccumulation factors than samples from soils with high concentration of contamination. Thus, a less contaminated soil could yield higher concentrations in earthworms compared to a higher contaminated soil. Assuming that when assessing risks with PCDD/F contaminated soil, a combination of chemical analysis of soil PCDD/Fs concentrations and bioavailability should be employed for a more comprehensive risk assessment.
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32.
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33.
  • Hollert, Henner, et al. (författare)
  • Biological and Chemical Determination of Dioxin-like Compounds in Sediments by Means of a Sediment Triad Approach in the Catchment Area of the River Neckar
  • 2002
  • Ingår i: Ecotoxicology. - 0963-9292 .- 1573-3017. ; 11:5, s. 323-36
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate the sediment quality of selected sites in the catchment area of the River Neckar, an integrative assessment approach was used to assess the ecological hazard potential of dioxin-like sediment compounds. The approach is based on 7-ethoxyresorufin-O -deethylase (EROD) induction in embryonic chicken liver culture and comprehensive chemical analyses of polycyclic aromatic hydrocarbons (priority PAHs according to the US Environmental Protection Agency). The majority of the sediment extracts exhibited high potencies as EROD-inducers. In one sediment sample, which was influenced by a sewage treatment plant, a very high concentration of 930 ng bioassay 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) equivalents (bio-TEQs )/g organic carbon could be determined. However, in none of the samples, more than 6% of the EROD-inducing potency could be explained by the PAHs analyzed chemically. Thus, non-analyzed compounds with EROD-inducing potency were present in the extracts. A fractionation of sediment samples according to pH allowed to localize the major part of EROD-inducing compounds in the neutral fractions. However, a significant portion of the EROD induction could also be explained by the acidic fractions. Following the concept of the Sediment Quality Triad according to Chapman, in situ alterations of macrozoobenthos were examined. A comparison of the results predicted by the EROD assay and chemical analyses with alterations in situ , as measured by means of the saprobic index and the ecotoxicological index according to Carmargo, revealed a high ecological relevance of the results of bioassays and chemical analyses for major sites.
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34.
  • Håkansson, H., et al. (författare)
  • In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
  • 1991
  • Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
  • Tidskriftsartikel (refereegranskat)abstract
    • Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
  •  
35.
  • Jacobsen, Annette V., et al. (författare)
  • Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos
  • 2018
  • Ingår i: Environmental Science and Pollution Research. - : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 25:23, s. 23074-23081
  • Tidskriftsartikel (refereegranskat)abstract
    • Per- and polyfluoroalkyl substances (PFAS) are synthetic surfactants with a wide variety of applications; however, due to their stability, they are particularly resistant to degradation and, as such, are classed as persistent organic pollutants. Perfluorooctane sulfonate (PFOS) is one such PFAS that is still detectable in a range of different environmental settings, despite its use now being regulated in numerous countries. Elevated levels of PFOS have been detected in various avian species, and the impact of this on avian health is of interest when determining acceptable levels of PFOS in the environment. Due to its similarities to naturally occurring fatty acids, PFOS has potential to disrupt a range of biological pathways, particularly those associated with lipid metabolism, and this has been shown in various species. In this study, we have investigated how in ovo exposure to environmentally relevant levels of PFOS affects expression of genes involved in lipid metabolism of developing chicken embryos. We have found a broad suppression of transcription of genes involved in fatty acid oxidation and PPAR-mediated transcription with more significant effects apparent at lower doses of PFOS. These results highlight the need for more research investigating the biological impacts of low levels of PFAS to properly inform environmental policy governing their regulation.
  •  
36.
  • Jernbro, Susanne, et al. (författare)
  • Perfluorooctane Sulfonate Increases the Genotoxicity of Cyclophosphamide in the Micronucleus Assay with V79 Cells : Further Proof of Alterations in Cell Membrane Properties Caused by PFOS
  • 2007
  • Ingår i: Environmental Science and Pollution Research. - : Ecomed. - 0944-1344 .- 1614-7499. ; 14:2, s. 85-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorooctane sulfonate (PFOS; C8F17SO3–) is a fully fluorinated organic compound which has been manufactured for decades and was used widely in industrial and commercial products. The recent toxicological knowledge of PFOS mainly concerns mono-substance exposures of PFOS to biological systems, leaving the potential interactive effects of PFOS with other compounds as an area where understanding is significantly lacking. However, a recent study, reported the potential of PFOS to enhance the toxicity of two compounds by increasing cell membrane permeability. This is of particular concern since PFOS has been reported to be widely distributed in the environment where contaminants are known to occur in complex mixtures. In this study, PFOS was evaluated alone and in combination with cyclophosphamide (CPP) to investigate whether a presence of PFOS leads to an increased genotoxic potential of CPP towards hamster lung V79 cells. Genotoxicity was investigated using the micronucleus(MN) assay according to the recent draft ISO/DIS 21427-2 method. PFOS alone demonstrated no genotoxicity up to a concentration of 12.5 μg/ml. However, PFOS combined with two different concentrations of CPP, with metabolic activation, caused a significant increase in the number of micronucleated cells compared to treatments with CPP alone. These results provide a first indication that PFOS has the potential to enhance the genotoxic action of CPP towards V79 cells, suggesting, together with the alterations in cell membrane properties shown previously, that genotoxicity of complex mixtures may be increased significantly by changes in chemical uptake. Together with an earlier study performed by the own working group, it can be concluded that PFOS alone is not genotoxic in this bioassay using V79 cells up to 12.5 μg/ml, but that further investigations are needed to assess the potential interaction between PFOS and other substances, in particular regarding the impact of membrane alterations on the uptake of toxic substances.
  •  
37.
  • Keiter, Susanne, et al. (författare)
  • Does perfluorooctane sulfonate (PFOS) act as chemosensitizer in zebrafish embryos?
  • 2016
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 548-549, s. 317-324
  • Tidskriftsartikel (refereegranskat)abstract
    • Earlier studies have shown that perfluorooctane sulfonate (PFOS) increases the toxicity of other chemicals by enhancing their uptake by cells and tissues. The present study aimed at testing whether the underlying mechanism of enhanced uptake of chemicals by zebrafish (Danio rerio) embryos in the presence of PFOS is by interference of this compound with the cellular efflux transporter Abcb4. Modifications of uptake/clearance and toxicity of two Abcb4 substrates, the fluorescent dye rhodamine B (RhB) and vinblastine, by PFOS were evaluated using 24 and 48. h post-fertilization (hpf) embryos. Upon 90. min exposure of 24. hpf embryos to 1. μM RhB and different PFOS concentrations (3-300. μM) accumulation of RhB in zebrafish was increased by up to 11.9-fold compared to controls, whereas RhB increases in verapamil treatments were 1.7-fold. Co-administration of PFOS and vinblastine in exposures from 0 to 48. hpf resulted in higher vinblastine-caused mortalities in zebrafish embryos indicating increased uptake of this compound. Interference of PFOS with zebrafish Abcb4 activity was further studied using recombinant protein obtained with the baculovirus expression system. PFOS lead to a concentration-dependent decrease of the verapamil-stimulated Abcb4 ATPase activity; at higher PFOS concentrations (250, 500. μM), also the basal ATPase activity was lowered indicating PFOS to be an Abcb4 inhibitor. In exposures of 48. hpf embryos to a very high RhB concentration (200. μM), accumulation of RhB in embryo tissue and adsorption to the chorion were increased in the presence of 50 or 100. μM PFOS. In conclusion, the results indicate that PFOS acts as inhibitor of zebrafish Abcb4; however, the exceptionally large PFOS-caused effect amplitude of RhB accumulation in the 1. μM RhB experiments and the clear PFOS effects in the experiments with 200. μM RhB suggest that an additional mechanism appears to be responsible for the potential of PFOS to enhance uptake of Abcb4 substrates.
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38.
  • Keiter, Su, et al. (författare)
  • Long-term effects of a binary mixture of perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) in zebrafish (Danio rerio)
  • 2012
  • Ingår i: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 118-119, s. 116-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous in vitro studies have reported the potential of perfluorooctane sulfonate (PFOS) to increase the toxicity of other compounds. Given the complex nature of mixtures of environmental pollutants in aquatic systems together with the persistent and bioaccumulative properties of PFOS, this study aimed at evaluating the long-term effects and toxicity-increasing behavior of PFOS in vivo using the zebrafish (Danio rerio). Fish were maintained in flow-through conditions and exposed to single and binary mixtures of PFOS and the endocrine disruptor bisphenol A (BPA) at nominal concentrations of 0.6, 100 and 300 mu g/L and 10, 200 and 400 mu g/L, respectively. F1 and F2 generations were evaluated from 0 to 180 days post-fertilization (dpf) and F3 generation was evaluated from 0 to 14 dpf. Survival was documented in all generations, whereas growth, fecundity, fertilization rate, histological alterations (in liver, thyroid and gonads) and vitellogenin (Vtg) induction in males were evaluated for Fl and F2 generations. Data for growth were collected at 30, 90 and 180 dpf and data for histological evaluations and Vtg induction were analyzed at 90 and 180 dpf. No significant effects on survival were seen in the Fl generation in any treatment following 180 d exposure: however, in the F2 generation, 300 mu g/L PFOS both alone and in combination with BPA (10, 200 and 400 mu g/L) induced 100% mortality within 14 dpf. PFOS (0.6 and 300 mu g/L) did not increase the Vtg-inducing potential of BPA (10, 200 and 400 mu g/L) in a binary mixture. In contrast, binary mixtures with 300 mu g/L PFOS suppressed the Vtg levels in Fl males at 90 dpf when compared to single BPA exposures. Whereas the lowest tested PFOS concentration (0.6 mu g/L) showed an estrogenic potential in terms of significant Vtg induction, Vtg levels were generally found to decrease with increasing PFOS-exposure in both Fl and F2 generations. In Fl generation, BPA-exposure was found to increase Vtg levels in a concentration-dependent manner. Histological analyses of Fl and F2 fish revealed hepatocellular vacuolization, predominantly in males, following PFOS-exposure both alone and in combination with BPA. Hepatotoxicity by PFOS might explain the suppressed Vtg response seen in PFOS-exposed Fl and F2 males. PFOS-exposed fish also showed granulomas, mainly in the liver. Given previous reports of the immunosuppressive potential of PFOS, the granulomas could be a consequence of a PFOS-induced reduction of the immune response potential. In conclusion, the hypothesis that the presence of PFOS increases the endocrine potential of BPA could not be confirmed in zebrafish. Adverse effects on liver structure and survival were only seen at concentrations well above ecologically relevant concentrations; however, the decline in survival rates following PFOS-exposure seen over generations again documents the importance of long-term studies for the investigation of persistent environmental pollutants.
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39.
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40.
  • Lam, Monika M., 1987- (författare)
  • Characterization of PAC-contaminated soil with the focus on availability, leachability and biological activities
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Current risk assessments of polycyclic aromatic compounds (PACs)-contaminated soil are often based on the 16 priority PAHs and do not consider availability of PACs in soil sufficiently. This may lead to uncertainties of the assessment, since important contaminants can be overlooked and only a small fraction of contaminants is available for the uptake for organisms. The overall aim of this thesis was to develop a refined and enhanced analytical approach based on both chemical and bioassay analysis coupled to passive sampling with polyoxymethylene (POM) and leaching tests that can provide a more comprehensive picture of chemical pollution at PAC-contaminated sites. To achieve this, bioassay-specific relative potency factors (REPs) of PACs were determined for the H4IIE-luc bioassay, detecting AhR-mediated activity, and for the VM7luc4E2 transactivation assay, detecting ER-mediated activity for the use in potency-balance analysis. Results of uptake-experiments of PACs in earthworms and POM suggested that POM is a suitable tool to study availability of AhR and ER agonists in soil. Availability and mobility of PACs in soil were investigated by the use of POM and leaching tests. The results of potency-balance analysis showed that in soil samples, in POM-fractions or in leachates, a large fraction of AhR- or ER-agonists remained unexplained, despite the use of a large number of REPs. In addition, coupling of chemical and biological analysis to passive sampling or leaching tests revealed that only a small fraction of the total mass of PACs in the soil is available or leachable in soil. The results suggests that the use of only the total concentration in soil while ignoring unknown toxicants will lead to great uncertainties in the risk assessment. Therefore, effect-based screening using bioassays, taking availability and mobility of compounds into account, as well as a widened chemical analysis should be included in modern hazard- and risk assessment of PAH contaminated soils.
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41.
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42.
  • Lam, Monika M., 1987-, et al. (författare)
  • Methylated PACs Are More Potent than Their Parent Compounds : A Study on AhR-mediated Activity, Degradability and Mixture Interactions in the H4IIE-luc Assay
  • 2018
  • Ingår i: Environmental Toxicology and Chemistry. - : John Wiley & Sons. - 0730-7268 .- 1552-8618. ; 37:5, s. 1409-1419
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty-six polycyclic aromatic compounds (PACs; including native polycyclic aromatic hydrocarbons [PAHs], hydroxylated PAHs, alkylated and oxygenated PAHs, and [alkylated] heterocyclic compounds) were investigated for their aryl hydrocarbon receptor (AhR)-mediated potencies in the H4IIE-luc bioassay. Potential degradabilities of PACs were investigated by use of various durations of exposure (24, 48, or 72 h), and various mixtures of PACs including PAHs, alkylated and oxygenated PAHs, and heterocyclic compounds were tested for their joint AhR-mediated potency. Additive behaviors of PACs in mixtures were studied by comparing observed mixture potencies with mixture potencies predicted by use of the concentration addition model. Methylated derivatives were more potent than their parent compounds in the H4IIE-luc assay. A time-dependent decrease in relative potency was observed for all AhR-active compounds, which may be indicative of in vitro biotransformation. Monomethylated compounds seemed to be more rapidly transformed than analogous unsubstituted compounds. In addition, the results showed that the predictive power of the concentration addition model increased with the number of compounds, suggesting additivity in multicomponent mixtures. Due to the greater potency of methylated derivatives and their ubiquitous occurrence, there is a need for further research on the toxicity and mixture behavior of these environmentally and toxicologically relevant compounds.
  •  
43.
  • Lam, Monika M., 1987-, et al. (författare)
  • Methylated polycyclic aromatic hydrocarbons and/or their metabolites are important contributors to the overall estrogenic activity of polycyclic aromatic hydrocarbon-contaminated soils
  • 2018
  • Ingår i: Environmental Toxicology and Chemistry. - : John Wiley & Sons. - 0730-7268 .- 1552-8618. ; 37:2, s. 385-397
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay. Relative potencies were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist vertical bar C vertical bar 182,780 (vertical bar C vertical bar) and the aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone. Luciferase induction and CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD) activity were measured to assess whether the estrogenic activity was elicited by the compound itself and/or by its metabolites. Relative potencies ranged between 10(-7) and 10(-4). The ability of ICI to decrease luciferase activity stimulated by all compounds indicated that the induction responses were ER-dependent. The aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone decreased luciferase induction and EROD activity by several compounds, including the methylated chrysenes, suggesting that metabolites of these chemicals contributed to ER activation. Several PACs, such as acridine and its derivatives, appear to directly activate the ER. Furthermore, extracts of soils from industrial areas were examined using this bioassay, and estrogenic activity was detected in all soil samples. Mass-balance analysis using a combination of relative potencies and chemical analysis of the samples suggested that polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, such as 1-and 3-methylchrysene, are important contributors to the overall estrogenic activity. However, these results revealed that a considerable proportion of the estrogenic activity in the soil remained unexplained, indicating the presence of other significant estrogenic compounds.
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44.
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45.
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46.
  • Larsson, Maria, 1975-, et al. (författare)
  • AhR-mediated activities of polycyclic aromatic compound (PAC) mixtures are predictable by the concept of concentration addition
  • 2014
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 73, s. 94-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Risk assessments of polycyclic aromatic hydrocarbons (PAHs) are complicated because these compounds exist in the environment as complex mixtures of hundreds of individual PAHs and other related polycyclic aromatic compounds (PACs). In this study, the hypothesis that concentration addition (CA) can be used to predict the aryl hydrocarbon receptor (AhR)-mediated activity of PACs in mixtures containing various combinations of PACs was tested. AhR-mediated activities of 18 mixtures composed of two to 23 PACs, which included PAHs, azaarenes and oxygenated PAHs, were examined by the use of the AhR-based H4IIE-luc bioassay. Since greater AhR-mediated activities have been observed in soils contaminated by PAHs, investigations were done to test whether soil extract matrix or the presence of non-effect PACs might affect responses of the H4IIE-luc bioassay. Our results showed that AhR-mediated activities of mixtures of PACs could be predicted by the use of concentration addition. Additive activities of PACs in multi component mixtures along with the insignificant effect of the soil matrix support the use of concentration addition in mass balance calculations and AhR-based bioassays in risk assessment of environmental samples. However, independent action (IA) could not be used to predict the activity of mixtures of PACs.
  •  
47.
  • Larsson, Maria, et al. (författare)
  • Chemical and bioanalytical characterisation of PAHs in risk assessment of remediated PAH-contaminated soils
  • 2013
  • Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 20:12, s. 8511-8520
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in soil at former industrial areas; and in Sweden, some of the most contaminated sites are being remediated. Generic guideline values for soil use after so-called successful remediation actions of PAH-contaminated soil are based on the 16 EPA priority pollutants, which only constitute a small part of the complex cocktail of toxicants in many contaminated soils. The aim of the study was to elucidate if the actual toxicological risks of soil samples from successful remediation projects could be reflected by chemical determination of these PAHs. We compared chemical analysis (GC-MS) and bioassay analysis (H4IIE-luc) of a number of remediated PAH-contaminated soils. The H4IIE-luc bioassay is an aryl hydrocarbon (Ah) receptor-based assay that detects compounds that activate the Ah receptor, one important mechanism for PAH toxicity. Comparison of the results showed that the bioassay-determined toxicity in the remediated soil samples could only be explained to a minor extent by the concentrations of the 16 priority PAHs. The current risk assessment method for PAH-contaminated soil in use in Sweden along with other countries, based on chemical analysis of selected PAHs, is missing toxicologically relevant PAHs and other similar substances. It is therefore reasonable to include bioassays in risk assessment and in the classification of remediated PAH-contaminated soils. This could minimise environmental and human health risks and enable greater safety in subsequent reuse of remediated soils.
  •  
48.
  • Larsson, Maria, 1975-, et al. (författare)
  • Occurrence and leachability of polycyclic aromatic compounds in contaminated soils : Chemical and bioanalytical characterization
  • 2018
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 622-623, s. 1476-1484
  • Tidskriftsartikel (refereegranskat)abstract
    • An important concern regarding sites contaminated with polycyclic aromatic compounds (PACs) is the risk of groundwater contamination by release of the compounds from soils. The goal of this study was to investigate the occurrence and leachability of 77 PACs including polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (NSO-PACs) among total aryl hydrocarbon receptor (AhR) agonists in soils from historical contaminated sites. A novel approach combining chemical and bioanalytical methods in combination with characterization of leachability by use of a column leaching test was used. Similar profiles of relative concentrations of PACs were observed in all soils, with parent PAHs accounting for 71 to 90% of total concentrations in soils. Contribution of oxy-PAHs, alkyl-PAHs and N-PACs ranged from 2 to 9%, 3 to 9% and 1 to 14%, respectively. Although the contributions of groups of PACs were small, some compounds were found in similar or greater concentrations than parent PAHs. Leachable fractions of 77 PACs from soils were small and ranged from 0.002 to 0.54%. Polar PACs were shown to be more leachable than parent PAHs. The contribution of analyzed PACS to overall AhR-mediated activities in soils and leachates suggests presence of other AhR agonists in soils, and a potential risk. Only a small fraction of AhR agonists was available in soils, indicating an overestimation of the risk if only total initial concentrations in soils would be considered in risk assessment. The results of the study strongly support that focus on 16US EPA PAHs may result in inadequate assessment of risk and hazard of PACs in complex environmental samples.
  •  
49.
  • Larsson, Maria, 1975-, et al. (författare)
  • Time-dependent relative potency factors for polycyclic aromatic hydrocarbons and their derivatives in the H4IIE-luc bioassay
  • 2014
  • Ingår i: Environmental Toxicology and Chemistry. - Hoboken : Wiley-Blackwell. - 0730-7268 .- 1552-8618. ; 33:4, s. 943-953
  • Tidskriftsartikel (refereegranskat)abstract
    • The H4IIE-luc transactivation bioassay for aryl hydrocarbon receptor (AhR) agonists was used to investigate the relative potency factors (REPs) of 22 individual polycyclic aromatic hydrocarbons (PAHs) and their oxygenated-, methylated-, and N-containing derivatives (azaarenes), which are often present in PAH-contaminated soils. Naphthacene and dibenz[ah]acridine exhibited greater AhR-mediated potency, whereas lesser molecular-weight azaarenes were less potent AhR agonists. Six oxygenated PAHs had calculable REPs, but their potencies were less than their parent PAHs. Unlike the parent, unsubstituted PAHs, oxidation of methylated PAHs seemed to increase the AhR-mediated potency of the compounds, with 2-methylanthracene-9,10-dione being almost 2 times more potent than 2-methylanthracene. Both bioassay and gas chromatography-mass spectrometry analysis were used to examine the exposure time-dependent effects on the REPs at 24 h, 48 h, and 72 h of exposure in the H4IIE-luc transactivation bioassay. Changes in concentrations of 5 compounds including the model reference 2,3,7,8-tetrachlorodibenzo-p-dioxin in the cell culture wells were measured, and the amounts in the cell medium, in the cells, and adsorbed to the wells was determined and the influence on the REPs was studied. Declining REP values with increased duration of exposure were shown for all compounds, which we concluded were a consequence of the metabolism of PAHs and PAH derivatives in H4IIe-luc cells. The present study provides new knowledge regarding the degradation and distribution of compounds in the wells during exposure. Environ Toxicol Chem 2014;33:943-953. (c) 2014 SETAC
  •  
50.
  • Le Du-Carrée, Jessy, et al. (författare)
  • Cocktail effects of tire wear particles leachates on diverse biological models : A multilevel analysis
  • 2024
  • Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 471
  • Tidskriftsartikel (refereegranskat)abstract
    • Tire wear particles (TWP) stand out as a major contributor to microplastic pollution, yet their environmental impact remains inadequately understood. This study delves into the cocktail effects of TWP leachates, employing molecular, cellular, and organismal assessments on diverse biological models. Extracted in artificial seawater and analyzed for metals and organic compounds, TWP leachates revealed the presence of polyaromatic hydrocarbons and 4-tert-octylphenol. Exposure to TWP leachates (1.5 to 1000 mg peq L-1) inhibited algae growth and induced zebrafish embryotoxicity, pigment alterations, and behavioral changes. Cell painting uncovered pro-apoptotic changes, while mechanism-specific gene-reporter assays highlighted endocrine-disrupting potential, particularly antiandrogenic effects. Although heavy metals like zinc have been suggested as major players in TWP leachate toxicity, this study emphasizes water-leachable organic compounds as the primary causative agents of observed acute toxicity. The findings underscore the need to reduce TWP pollution in aquatic systems and enhance regulations governing highly toxic tire additives.
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