| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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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
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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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)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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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)
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Perfluorooctane sulfonate increases β-oxidation of palmitic acid in chicken liver
- 2012
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Ingår i: Environmental Science and Pollution Research. - Heidelberg, Germany : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 19:5, s. 1859-1863
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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)
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Microplastics in the marine environment and the assessment of potential adverse effects of associated chemicals
- 2019
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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)
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Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 183
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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)
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NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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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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| 7. |
- Alijagic, Andi, 1992-, et al.
(författare)
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The triple exposure nexus of microplastic particles, plastic-associated chemicals, and environmental pollutants from a human health perspective
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 188
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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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| 8. |
- Behnisch, Peter, et al.
(författare)
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Results of an international interlaboratory study on dioxin-like activities in drinking-, river surface- and wastewater using DR CALUX bioassay
- 2024
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 920
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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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| 9. |
- Beiras, R., et al.
(författare)
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Ingestion and contact with polyethylene microplastics does not cause acute toxicity on marine zooplankton
- 2018
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 360, s. 452-460
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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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| 10. |
- Brunström, Björn, et al.
(författare)
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EROD induction in cultured chick embryo liver : a sensitive bioassay for dioxin-like environmental pollutants
- 1995
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 14:5, s. 837-842
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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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