| 1. |
- Lupu, Diana, et al.
(författare)
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The ENDpoiNTs Project : Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.
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| 2. |
- Audouze, Karine, et al.
(författare)
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Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways : Challenges and Opportunities
- 2021
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- A transformation of regulatory toxicology is underway to meet the demands of testing increasing numbers of chemicals whilst reducing reliance on in vivo models. This transformation requires a shift from chemical safety assessment largely based on direct empirical observation of apical toxicity outcomes in whole organisms to predictive approaches in which outcomes and risks are inferred from accumulated mechanistic understanding.
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| 3. |
- Gustafsson, Johan, 1991-
(författare)
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Exposure and effects of naturally produced hydroxylated polybrominated diphenyl ethers in fish : Implications for Baltic Sea wildlife
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate if naturally produced hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are causing negative health effects for Baltic Sea wildlife. In the laboratory, OH-PBDEs have shown to be potent disrupters of energy metabolism as well as endocrine disruptors and neurotoxins. OH-PBDEs are naturally produced, for example, by filamentous macroalgae in the Baltic Sea but are also metabolites of the flame retardants polybrominated diphenyl ethers (PBDEs). High concentrations of OH-PBDEs have been detected in several species in the Baltic Sea, including the European perch (Perca fluviatilis). The concentrations of OH-PBDEs in perch, and some other species from the Baltic Sea, are within reported toxicological effect concentrations.In this thesis, perch were sampled approximately once a week during an exposure peak of OH-PBDEs between May and October in 2018. In Paper I, correlations between OH-PBDEs and several health biomarkers in perch were studied. A higher OH-PBDE concentration correlated with increased ethoxyresorufin-O-deethylase (EROD) activity, increased plasma lactate concentration, increased plasma glucose concentration, decreased lipid percentage in muscle, and decreased liver somatic index. These correlations indicate that OH-PBDEs might cause negative health effects in perch from the Baltic Sea.Many aquatic species in the Baltic Sea have been reported to suffer from thiamine (vitamin B1) deficiency. Thiamine deficiency could be a confounding factor when assessing potential in vivo effects of OH-PBDEs. Hence, in Paper II, the thiamine status of perch was investigated. Perch were found to have sufficient thiamine, thus thiamine deficiency is not a confounding factor when assessing potential effects of OH-PBDEs in perch from the Baltic Sea.In Paper III, metabolomics was performed on zebrafish (Danio rerio) embryos exposed to OH-PBDEs. The aim was to study the toxicity of OH-PBDEs at the metabolome level and to identify selective and sensitive biomarker(s) for energy disruption of OH-PBDEs. OH-PBDEs were found to cause diverse metabolic effects at environmentally relevant concentrations. Accumulation of succinic acid, a key metabolite for energy production and regulation of the immune system, was suggested as a potential biomarker for energy disruption due to OH-PBDEs. In Paper IV, lipids and 19 polar metabolites, including metabolites observed to be affected by OH-PBDEs in Paper III, were analysed in perch from the Baltic Sea. Among other findings, a correlation between increased OH-PBDE exposure and increased concentration of succinic acid was observed. The correlations observed in the perch to a large extent agreed with the metabolic effects seen in zebrafish embryos exposed to OH-PBDEs (Paper III), indicating potential causality between exposure to OH-PBDEs and effects in perch from the Baltic Sea.The correlations observed in this thesis between OH-PBDEs and biomarkers in perch should be interpreted with caution as the correlations could be spurious, for example caused by underlying environmental factors. However, taken together, the results support the hypothesis that naturally produced OH-PBDEs could cause negative health effects in perch from the Baltic Sea.
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| 4. |
- Gustafsson, Johan, et al.
(författare)
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Metabolite alterations in zebrafish embryos exposed to hydroxylated polybrominated diphenyl ethers
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 857
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system. This is the first study focusing on the effects of OH-PBDEs at the metabolite level in vivo. The aim of the current study was to investigate the metabolic effects of exposure to OH-PBDEs using metabolomics, and to identify potential biomarker(s) for energy disruption of OH-PBDEs. Zebrafish (Danio rerio) embryos were exposed to two different concentrations of 6-OH-BDE47 and 6-OH-BDE85 and a mixture of these two compounds. In total, 342 metabolites were annotated and 79 metabolites were affected in at least one exposure. Several affected metabolites, e.g. succinic acid, glutamic acid, glutamine, tyrosine, tryptophan, adenine, and several fatty acids, could be connected to known toxic mechanisms of OH-PBDEs. Several phospholipids were strongly up-regulated with up to a six-fold increase after exposure to 6-OH-BDE47, a scarcely described effect of OH-PBDEs. Based on the observed metabolic effects, a possible connection between disruption of the energy metabolism, neurotoxicity and potential immunotoxicity of OH-PBDEs was suggested. Single compound exposures to 6-OH-BDE47 and 6-OH-BDE85 showed little overlap in the affected metabolites. This shows that compounds of similar chemical structure can induce different metabolic effects, possibly relating to their different toxic mechanisms. There were inter-concentration differences in the metabolic profiles, indicating that the metabolic effects were concentration dependent. After exposure to the mixture of 6-OH-BDE47 and 6-OH-BDE85, a new metabolic profile distinct from the profiles obtained from the single compounds was observed. Succinic acid was up-regulated at the highest, but still environmentally relevant, concentration of 6-OH-BDE47, 6-OH-BDE85, and the mixture. Therefore, succinic acid is suggested as a potential biomarker for energy disruption of OH-PBDEs.
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| 5. |
- Van Der Veen, Ike, et al.
(författare)
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Fate of Per- and Polyfluoroalkyl Substances from Durable Water-Repellent Clothing during Use
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society. - 0013-936X .- 1520-5851. ; 56:9, s. 5886-5897
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Tidskriftsartikel (refereegranskat)abstract
- To make outdoor clothing water- or dirt-repellent, durable water-repellent (DWR) coatings based on side-chain fluorinated polymers (SFPs) are used. During use of outdoor clothing, per- and polyfluoroalkyl substances (PFASs) can be emitted from the DWR to the environment. In this study, the effects of aging, washing, and tumble drying on the concentration of extractable PFASs in the DWR of perfluorohexane-based short-chain SFPs (FC-6 chemistry) and of perfluorooctane-based long-chain SFPs (FC-8 chemistry) were assessed. For this purpose, polyamide (PA) and polyester (PES) fabrics were coated with FC-6- and FC-8-based DWRs. Results show that aging of the coated fabrics causes an increase in concentration and formation of perfluoroalkyl acids (PFAAs). The effect of aging on the volatile PFASs depends on the type of fabric. Washing causes a decrease in PFAA concentrations, and in general, volatile PFASs are partly washed out of the textiles. However, washing can also increase the extractable concentration of volatile PFASs in the fabrics. This effect becomes stronger by a combination of aging and washing. Tumble drying does not affect the PFAS concentrations in textiles. In conclusion, aging and washing of fabrics coated with the DWR based on SFPs release PFASs to the environment.
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