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Towards risk governance of nanomaterials: adaptation and validation of test methods for characterization and hazard assessment

Longhin, Eleonora Marta; Doak, Shareen H.; Lynch, Iseult; Moschini, Elisa; Rundén-Pran, Elise; El Yamani, Naouale; Bouman, Evert; Burgum, Michael J.; Reilly, Katie; Cambier, Sebastien; Gutleb, Arno C.; Cimpan, Mihaela-Roxana; Rios-Mondragon, Ivan; Xue, Ying; Cimpan, Emil; Puzyn, Tomasz; Sosnowska, Anita; Fessard, Valérie; Varet, Julie; Vinković Vrček, Ivana; Pem, Barbara; de la Fuente, Jesus Martinez; Sánchez del Castillo, Victor Manuel; Cuestas Ayllón, Carlos; Hoet, Peter; Murugadoss, Sivakumar; de Souza Nunes, Juliana; Lopez, Aitziber; Dupin, Damien; Ghahremani, MH; Gharailou, D; Badetti, Elena; Brunelli, Andrea; Isigonis, Panagiotis; Afantitis, Antreas; Melagraki, Georgia; Bohmer, Nils; Malsch, Ineke; Dusinska, Maria

2022

Genotoxicity assessment of lung cells cultured at the air-liquid interface: comparison of bronchial and alveolar mono- and cocultures

Elje, Elisabeth; McFadden, Erin; Mariussen, Espen; Dusinska, Maria; Rundén-Pran, Elise

2022

Validation of an advanced 3D respiratory tri-culture model at the air-liquid interface for hazard assessment of nanomaterials

Camassa, Laura Maria Azzurra; Elje, Elisabeth; Mariussen, Espen; Longhin, Eleonora Marta; Haugen, Kristine; Dusinska, Maria; Zienolddiny-Narui, Shan; Rundén-Pran, Elise

2022

Decitabine-induced DNA methylation-mediated transcriptomic reprogramming in human breast cancer cell lines; the impact of DCK overexpression

Buociková, Verona; Tyciakova, Sylvia; Pilalis, Eleftherios; Mastrokalou, Chara; Urbanova, Maria; Matuskova, Miroslava; Demkova, Lucia; Medova, Veronika; Longhin, Eleonora Marta; Rundén-Pran, Elise; Dusinska, Maria; Rios Mondragon, Ivan; Cimpan, Mihaela-Roxana; Gábelová, Alena; Soltysova, Andrea; Smolkova, Bozena; Chatziioannou, Aristotelis

Decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, is tested in combination with conventional anticancer drugs as a treatment option for various solid tumors. Although epigenome modulation provides a promising avenue in treating resistant cancer types, more studies are required to evaluate its safety and ability to normalize the aberrant transcriptional profiles. As deoxycytidine kinase (DCK)-mediated phosphorylation is a rate-limiting step in DAC metabolic activation, we hypothesized that its intracellular overexpression could potentiate DAC’s effect on cell methylome and thus increase its therapeutic efficacy. Therefore, two breast cancer cell lines, JIMT-1 and T-47D, differing in their molecular characteristics, were transfected with a DCK expression vector and exposed to low-dose DAC (approximately IC20). Although transfection resulted in a significant DCK expression increase, further enhanced by DAC exposure, no transfection-induced changes were found at the global DNA methylation level or in cell viability. In parallel, an integrative approach was applied to decipher DAC-induced, methylation-mediated, transcriptomic reprogramming. Besides large-scale hypomethylation, accompanied by up-regulation of gene expression across the entire genome, DAC also induced hypermethylation and down-regulation of numerous genes in both cell lines. Interestingly, TET1 and TET2 expression halved in JIMT-1 cells after DAC exposure, while DNMTs’ changes were not significant. The protein digestion and absorption pathway, containing numerous collagen and solute carrier genes, ranking second among membrane transport proteins, was the top enriched pathway in both cell lines when hypomethylated and up-regulated genes were considered. Moreover, the calcium signaling pathway, playing a significant role in drug resistance, was among the top enriched in JIMT-1 cells. Although low-dose DAC demonstrated its ability to normalize the expression of tumor suppressors, several oncogenes were also up-regulated, a finding, that supports previously raised concerns regarding its broad reprogramming potential. Importantly, our research provides evidence about the involvement of active demethylation in DAC-mediated transcriptional reprogramming.

Frontiers Media S.A.

2022

Particle Precipitation Effects on the Global Secondary Ozone Distribution

Espy, Patrick Joseph; Murberg, Lise Eder; Løvset, Tiril; Orsolini, Yvan J.

2022

Nord Stream leak may have been largest methane emission ever recorded

Thompson, Rona Louise; Platt, Stephen Matthew (intervjuobjekter); Dinneen, James (journalist)

2022

Comparison of young male mice of two different strains (C57BL/6J and the hybrid B6129SF1/J) in selected behavior tests. A small scale study

Hansen, Kristine Eraker Aasland; Hudecova, Alexandra Misci; Haugen, Fred; Skjerve, Eystein; Ropstad, Erik; Zimmer, Karin Elisabeth

BACKGROUND
All mouse strains are different, before choosing a strain for a large study, a small scale study should be done. In this study, we compared young males of two mouse strains, C57BL/6J and the hybrid B6129SF1/J, and gained knowledge on their performance in three different behavioral tests; open field (OF) test, Barnes maze (BM) test and a restraint stress test.

RESULTS
We found that the young males of the C57BL/6J strain spent more time moving in the OF. In the BM, the hybrid covered less ground before reaching the goal box during the first three sessions, than the C57BL/6J. The hybrid left more fecal pellets than C57BL/6J both in OF and BM. During the stress test, the C57BL/6J had a lower corticosterone response than the hybrid.

CONCLUSIONS
Our findings indicate that the C57BL/6J has a presumably higher locomotor activity and/or explorative behavior than the hybrid, while the hybrid appeared more sensitive to stress.

BioMed Central (BMC)

2022

Clean air policies are key for successfully mitigating Arctic warming

von Salzen, Knut; Whaley, Cynthia; Anenberg, Susan C.; Van Dingenen, Rita; Klimont, Zbigniew; Flanner, Mark G.; Mahmood, Rashed; Arnold, Stephen R.; Beagley, Stephen; Chien, Rong-You; Christensen, Jesper H.; Eckhardt, Sabine; Ekman, Annica M. L.; Evangeliou, Nikolaos; Faluvegi, Greg; Fu, Joshua S.; Gauss, Michael; Gong, Wanmin; Hjorth, Jens; Im, Ulas; Krishnan, Srinath; Kupiainen, Kaarle; Kuhn, Thomas; Langner, Joakim; Law, Kathy S.; Marelle, Louis; Oliviè, Dirk Jan Leo; Onishi, Tatsuo; Oshima, Naga; Paunu, Ville-Veikko; Peng, Yiran; Plummer, David; Pozzoli, Luca; Rao, Shilpa; Raut, Jean-Christophe; Sand, Maria; Schmale, Julia; Sigmond, Michael; Thomas, Manu Anna; Tsigaridis, Kostas; Tsyro, Svetlana; Turnock, Steven T.; Wang, Minqi; Winter, Barbara

A tighter integration of modeling frameworks for climate and air quality is urgently needed to assess the impacts of clean air policies on future Arctic and global climate. We combined a new model emulator and comprehensive emissions scenarios for air pollutants and greenhouse gases to assess climate and human health co-benefits of emissions reductions. Fossil fuel use is projected to rapidly decline in an increasingly sustainable world, resulting in far-reaching air quality benefits. Despite human health benefits, reductions in sulfur emissions in a more sustainable world could enhance Arctic warming by 0.8 °C in 2050 relative to the 1995–2014, thereby offsetting climate benefits of greenhouse gas reductions. Targeted and technically feasible emissions reduction opportunities exist for achieving simultaneous climate and human health co-benefits. It would be particularly beneficial to unlock a newly identified mitigation potential for carbon particulate matter, yielding Arctic climate benefits equivalent to those from carbon dioxide reductions by 2050.

2022

Integument carotenoid-based colouration reflects contamination to perfluoroalkyl substances, but not mercury, in arctic black-legged kittiwakes

Costantini, David; Blévin, Pierre; Bustnes, Jan Ove; Esteve, Valérie; Gabrielsen, Geir Wing; Herzke, Dorte; Humann-Guilleminot, Ségolène; Moe, Børge; Parenteau, Charline; Récapet, Charlotte; Bustamante, Paco; Chastel, Olivier

Anthropogenic activities are introducing multiple chemical contaminants into ecosystems that act as stressors for wildlife. Perfluoroalkyl substances (PFAS) and mercury (Hg) are two relevant contaminants that may cause detrimental effects on the fitness of many aquatic organisms. However, there is a lack of information on their impact on the expression of secondary sexual signals that animals use for mate choice. We have explored the correlations between integument carotenoid-based colourations, blood levels of carotenoids, and blood levels of seven PFAS and of total Hg (THg) in 50 adult male black-legged kittiwakes (Rissa tridactyla) from the Norwegian Arctic during the pre-laying period, while controlling for other colouration influencing variables such as testosterone and body condition. Kittiwakes with elevated blood concentrations of PFAS (PFOSlin, PFNA, PFDcA, PFUnA, or PFDoA) had less chromatic but brighter bills, and brighter gape and tongue; PFOSlin was the pollutant with the strongest association with bill colourations. Conversely, plasma testosterone was the only significant correlate of hue and chroma of both gape and tongue, and of hue of the bill. Kittiwakes with higher concentrations of any PFAS, but not of THg, tended to have significantly higher plasma concentrations of the carotenoids astaxanthin, zeaxanthin, lutein, and cryptoxanthin. Our work provides the first correlative evidence that PFAS exposure might interfere with the carotenoid metabolism and the expression of integument carotenoid-based colourations in a free-living bird species. This outcome may be a direct effect of PFAS exposure or be indirectly caused by components of diet that also correlate with elevated PFAS concentrations (e.g., proteins). It also suggests that there might be no additive effect of THg co-exposure with PFAS on the expression of colourations. These results call for further work on the possible interference of PFAS with the expression of colourations used in mate choice.

Frontiers Media S.A.

2022

Impact of the Pacific sector sea ice loss on the sudden stratospheric warming characteristics

Zhang, Jiarong; Orsolini, Yvan J.; Limpasuvan, Varavut; Ukita, Jinro

The atmospheric response to Arctic sea ice loss remains a subject of much debate. Most studies have focused on the sea ice retreat in the Barents-Kara Seas and its troposphere-stratosphere influence. Here, we investigate the impact of large sea ice loss over the Chukchi-Bering Seas on the sudden stratospheric warming (SSW) phenomenon during the easterly phase of the Quasi-Biennial Oscillation through idealized large-ensemble experiments based on a global atmospheric model with a well-resolved stratosphere. Although culminating in autumn, the prescribed sea ice loss induces near-surface warming that persists into winter and deepens as the SSW develops. The resulting temperature contrasts foster a deep cyclonic circulation over the North Pacific, which elicits a strong upward wavenumber-2 activity into the stratosphere, reinforcing the climatological planetary wave pattern. While not affecting the SSW occurrence frequency, the amplified wave forcing in the stratosphere significantly increases the SSW duration and intensity, enhancing cold air outbreaks over the continents afterward.

2022

Norges målenettverk for luftkvalitet. Gjennomgang av stasjonsplasseringer i forhold til krav i EUs luftkvalitetsdirektiver.

Hak, Claudia

Rapporten gir en oversikt over Norges luftkvalitetsmålenettverk. Alle målestasjoner som rapporterer måledata til EEA/ESA er beskrevet og plasseringen er vurdert i forhold til krav i EUs direktiver.
Omgivelsene til stasjonene er beskrevet og viktige kilder til utslipp er identifisert. Plasseringen av målestasjonene er dokumentert med kart og flybilde og retningsvisende fotografier av området.
Avvik fra plasseringskriteriene er dokumentert. Anbefalinger for justeringer er gitt for enkelte stasjoner.

NILU

2022

Comparisons between the distributions of dust and combustion aerosols in MERRA-2, FLEXPART, and CALIPSO and implications for deposition freezing over wintertime Siberia

Zamora, Lauren M; Kahn, Ralph A.; Evangeliou, Nikolaos; Zwaaftink, Christine Groot; Huebert, Klaus B

Aerosol distributions have a potentially large influence on climate-relevant cloud properties but can be difficult to observe over the Arctic given pervasive cloudiness, long polar nights, data paucity over remote regions, and periodic diamond dust events that satellites can misclassify as aerosol. We compared Arctic 2008–2015 mineral dust and combustion aerosol distributions from the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite, the Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) reanalysis products, and the FLEXible PARTicle (FLEXPART) dispersion model. Based on coincident, seasonal Atmospheric Infrared Sounder (AIRS) Arctic satellite meteorological data, diamond dust may occur up to 60 % of the time in winter, but it hardly ever occurs in summer. In its absence, MERRA-2 and FLEXPART each predict the vertical and horizontal distribution of large-scale patterns in combustion aerosols with relatively high confidence (Kendall tau rank correlation > 0.6), although a sizable amount of variability is still unaccounted for. They do the same for dust, except in conditions conducive to diamond dust formation where CALIPSO is likely misclassifying diamond dust as mineral dust and near the surface...

2022

LP-39 TWINALT project – an excellent opportunity to exchange knowledge on alternative methods for toxicity assessment

Roszak, J.; Sobańska, Z.; Wolniakowska, A.; Marinovich, M.; Dusinska, Maria; Rundén-Pran, Elise; Vanhaecke, T.; Reszka, E.

Elsevier

2022

The colony forming efficiency assay for toxicity testing of nanomaterials – Modifications for higher-throughput

Rundén-Pran, Elise; Mariussen, Espen; El Yamani, Naouale; Elje, Elisabeth; Longhin, Eleonora Marta

To cope with the high number of nanomaterials manufactured, it is essential to develop high-throughput methods for in vitro toxicity screening. At the same time, the issue with interference of the nanomaterial (NM) with the read-out or the reagent of the assay needs to be addressed to avoid biased results. Thus, validated label-free methods are urgently needed for hazard identification of NMs to avoid unintended adverse effects on human health. The colony forming efficiency (CFE) assay is a label- and interference-free method for quantification of cytotoxicity by cell survival and colony forming efficiency by CFE formation. The CFE has shown to be compatible with toxicity testing of NMs. Here we present an optimized protocol for a higher-throughput set up.

Frontiers Media S.A.

2022

Gassutslipp skaper klimabekymring

Platt, Stephen Matthew (intervjuobjekt)

2022

Nye beregninger viser dobbelt så mye metan over Skandinavia

Platt, Stephen Matthew; Samset, Bjørn Hallvard (intervjuobjekter); Elster, Kristian (journalist)

2022

ACTRIS Data Centre.

Myhre, C. L.; Mona, L.; O'Connor, E.; Descloitres, J.; Fjæraa, A. M.; Fiebig, M.; Amato, F.; D'Amico, G.

2022

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020–2030

Zare Jeddi, Maryam; Hopf, Nancy B.; Louro, Henriqueta; Viegas, Susana; Galea, Karen S.; Pasanen-Kase, Robert; Santonen, Tiina; Mustieles, Vicente; Fernandez, Mariana F.; Verhagen, Hans; Bopp, Stephanie K.; Antignac, Jean Philippe; David, Arthur; Mol, Hans; Barouki, Robert; Audouze, Karine; Duca, Radu-Corneliu; Fantke, Peter; Scheepers, Paul; Ghosh, Manosij; Van Nieuwenhuyse, An; Lobo Vicente, Joana; Trier, Xenia; Rambaud, Loïc; Fillol, Clémence; Denys, Sebastien; Conrad, André; Kolossa-Gehring, Marike; Paini, Alicia; Arnot, Jon; Schulze, Florian; Jones, Kate; Sepai, Ovnair; Ali, Imran; Brennan, Lorraine; Benfenati, Emilio; Cubadda, Francesco; Mantovani, Alberto; Bartonova, Alena; Connolly, Alison; Slobodnik, Jaroslav; Bruinen de Bruin, Yuri; van Klaveren, Jacob; Palmen, Nicole; Dirven, Hubert; Husøy, Trine; Thomsen, Cathrine; Virgolino, Ana; Röösli, Martin; Gant, Tim; von Goetz, Natalie; Bessems, Jos

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission’s Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures.

In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders.

HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.

Elsevier

2022

EMEP modelling of carbonaceous aerosols in Europe: status and issues

Simpson, David; van der Gon, Hugo A.C. Denier; Kuenen, Jeroen; Yttri, Karl Espen

2022

Enhanced electrochemical degradation of acetaminophen in aqueous environments at oxygen-activated carbon felt anodes

Jakobczyk, Pawel; Skowierzak, Grzegorz; Kaczmarzyk, Iwona; Nadolska, Malgorzata; Wcislo, Anna; Lota, Katarzyna; Bogdanowicz, Robert; Ossowski, Tadeusz; Rostkowski, Pawel; Lota, Gregorz; Ryl, Jacek

2022

Lack of mutagenicity of TiO2 nanoparticles in vitro despite cellular and nuclear uptake

El Yamani, Naouale; Rubio, Laura; García-Rodríguez, Alba; Kažimírová, Alena; Rundén-Pran, Elise; Barančoková, Magdaléna; Marcos, Ricard; Dusinska, Maria

The potential genotoxicity of titanium dioxide (TiO2) nanoparticles (NPs) is a conflictive topic because both positive and negative findings have been reported. To add clarity, we have carried out a study with two cell lines (V79–4 and A549) to evaluate the effects of TiO2 NPs (NM-101), with a diameter ranging from 15 to 60 nm, at concentrations 1–75 μg/cm2. Using two different dispersion procedures, cell uptake was determined by Transmission Electron Microscopy (TEM). Mutagenicity was evaluated using the Hprt gene mutation test, while genotoxicity was determined with the comet assay, detecting both DNA breaks and oxidized DNA bases (with formamidopyrimidine glycosylase - Fpg). Cell internalization, as determined by TEM, shows TiO2 NM-101 in cytoplasmic vesicles, as well as close to and inside the nucleus. Such internalization did not depend on the state of agglomeration, nor the dispersion used. In spite of such internalization, no cytotoxicity was detected in V79–4 cells (relative growth activity and plating efficiency assays) or in A549 cells (AlamarBlue assay) after exposure lasting for 24 h. However, a significant decrease in the relative growth activity was detected at longer exposure times (48 and 72 h) and at the highest concentration 75 µg/cm2. When the modified enzyme-linked alkaline comet assay was performed on A549 cells, although no significant induction of DNA damage was detected, a positive concentration-effects relationship was observed (Spearman’s correlation = 0.9, p 0.0001). Furthermore, no significant increase of DNA oxidized purine bases was observed. When the frequency of Hprt gene mutants was determined in V79–4 cells, no increase was observed in the exposed cells, relative to the unexposed cultures. Our general conclusion is that, under our experimental conditions, TiO2 NM-101 exposure does not exert mutagenic effects despite the evidence of NP uptake by V79–4 cells.

2022

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