| 1. |
- Mohammed Taha, Hiba, et al.
(författare)
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The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
- 2022
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
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| 2. |
- Dulio, Valeria, et al.
(författare)
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The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate!
- 2020
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1
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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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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
- Ouyang, Xiyu, et al.
(författare)
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Non-target analysis of household dust and laundry dryer lint using comprehensive two-dimensional liquid chromatography coupled with time-of-flight mass spectrometry
- 2017
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 166, s. 431-437
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Tidskriftsartikel (refereegranskat)abstract
- Household dust and laundry dryer lint are important indoor environmental matrices that may have notable health effects on humans due to chronic exposure. However, due to the sample complexity the studies conducted on these sample matrices until now were almost exclusively on the basis of target analysis. In this study, comprehensive two-dimensional liquid chromatography coupled with time-of flight mass spectrometry (LC x LC-ToF MS) was applied, to enable non-target analysis of household dust as well as laundry dryer lint for the first time. The higher peak capacity and, good orthogonality of LC x LC, together with reduced ion suppression in the MS enabled rapid identification of environmental contaminants in these complex sample matrices. A number of environmental contaminants were tentatively identified based on their accurate masses and isotopic patterns, including plasticizers, flame retardants, pesticides, drug metabolites, etc. The identity of seven compounds: tris(2-butoxyethyl) phosphate, tris(2-chloropropyl) phosphate, n-benzyl butyl phthalate, dibutyl phthalate, tributyl phosphate, triethyl phosphate and N, N-diethyl-meta-toluamide was confirmed using two-dimensional retention alignment and their concentrations in the samples were semi-quantitatively determined.
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| 8. |
- Weiss, Jana M, et al.
(författare)
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Competitive Binding of Poly- and Perfluorinated Compounds to the Thyroid Hormone Transport Protein Transthyretin
- 2009
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Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press of the Society of Toxicology. - 1096-0929. ; 109:2, s. 206-16
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Tidskriftsartikel (refereegranskat)abstract
- Due to their unique surfactant properties, poly- and perfluorinated compounds (PFCs) have been extensively used, and can be found all over the environment.. Concern about their environmental fate and toxicological properties have initiated several research projects. In the present study, we investigated if PFCs can compete with thyroxin (T4, i.e. the transport form of thyroid hormone) for binding to the human thyroid hormone transport protein transthyretin (TTR). Such competitive capacity may lead to decreased thyroid hormone levels as previously reported for animals exposed to PFCs. Twenty four PFCs, together with six structurally similar natural fatty acids, were tested for binding capacity in a radioligand binding assay. The binding potency decreased in the order: PFHxS>PFOS/PFOA>PFHpA>L-PFOSi>PFNA, with TTR binding potencies 12.5-50 times lower than the natural ligand thyroxine (T4). Some lower molecular weight compounds with structural similarity to these PFCs were >100 times less potent than T4. Simple descriptors based on the two dimensional molecular structures of the compounds were used to visualize the chemical variation and to model the structure-activity relationship for the competitive potencies of the TTR-binding compounds. The models indicated the dependence on molecular size and functional group(s), but demanded a more detailed description of the chemical properties and data for validation and further QSAR development. Competitive binding of PFCs to TTR as observed for human TTR in the present study, may explain altered thyroid hormone levels described for PFC-exposed rats and monkeys. Median human blood levels of the most potent TTR-binding PFCs are 1-2 orders of magnitude lower than IC50-values determined in the present study. In addition, this study contributes to the understanding of the bioaccumulation of PFCs in man and possibly in other wildlife species.
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| 9. |
- Weiss, Jana M., et al.
(författare)
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Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats
- 2021
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; :28, s. 39001-39013
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Tidskriftsartikel (refereegranskat)abstract
- Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler's exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4-160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (r(S)=0.32, p<0.049) and PFUnDA (r(S)=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (r(S)=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (r(S)=0.46, p<0.01), PFUnDA (r(S)=0.40, p<0.05), PFDoDA (r(S)=0.44, p<0.01), and sum PFAS (r(S)=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat's health.
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| 10. |
- Weiss, Jana M., et al.
(författare)
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Tracing thyroid hormone-disrupting compounds : database compilation and structure-activity evaluation for an effect-directed analysis of sediment
- 2015
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 407:19, s. 5625-5634
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Tidskriftsartikel (refereegranskat)abstract
- A variety of anthropogenic compounds has been found to be capable of disrupting the endocrine systems of organisms, in laboratory studies as well as in wildlife. The most widely described endpoint is estrogenicity, but other hormonal disturbances, e.g., thyroid hormone disruption, are gaining more and more attention. Here, we present a review and chemical characterization, using principal component analysis, of organic compounds that have been tested for their capacity to bind competitively to the thyroid hormone transport protein transthyretin (TTR). The database contains 250 individual compounds and technical mixtures, of which 144 compounds are defined as TTR binders. Almost one third of these compounds (n = 52) were even more potent than the natural hormone thyroxine (T-4). The database was used as a tool to assist in the identification of thyroid hormone-disrupting compounds (THDCs) in an effect-directed analysis (EDA) study of a sediment sample. Two compounds could be confirmed to contribute to the detected TTR-binding potency in the sediment sample, i.e., triclosan and nonylphenol technical mixture. They constituted less than 1 % of the TTR-binding potency of the unfractionated extract. The low rate of explained activity may be attributed to the challenges related to identification of unknown contaminants in combination with the limited knowledge about THDCs in general. This study demonstrates the need for databases containing compound-specific toxicological properties. In the framework of EDA, such a database could be used to assist in the identification and confirmation of causative compounds focusing on thyroid hormone disruption.
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