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Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation
Get PDFData suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.publishedVersio
Risk assessment of consumer spray products using in vitro lung surfactant function inhibition, exposure modelling and chemical analysis
Get PDFConsumer spray products release aerosols that can potentially be inhaled and reach the deep parts of the lungs. A thin layer of liquid, containing a mixture of proteins and lipids known as lung surfactant, coats the alveoli. Inhibition of lung surfactant function can lead to acute loss of lung function. We focused on two groups of spray products; 8 cleaning and 13 impregnation products, and in the context of risk assessment, used an in vitro method for assessing inhibition of lung surfactant function. Original spray-cans were used to generate aerosols to measure aerodynamic particle size distribution. We recreated a real-life exposure scenario to estimate the alveolar deposited dose. Most impregnation products inhibited lung surfactant function at the lowest aerosolization rate, whereas only two cleaning products inhibited function at the highest rates. We used inhibitory dose and estimated alveolar deposition to calculate the margin of safety (MoS). The MoS for the inhibitory products was ≤1 for the impregnation products, while much larger for the cleaning products (>880). This risk assessment focused on the risk of lung surfactant function disruption and provides knowledge on an endpoint of lung toxicity that is not investigated by the currently available OECD test guidelines.publishedVersio
Estimation of the historical dry deposition of air pollution indoors to the monumental paintings by Edvard Munch in the University Aula, in Oslo, Norway
Get PDFThe historical (1835–2020) deposition of major air pollutants (SO2, NOx, O3 and PM2.5) indoors, as represented by the monumental Edvard Munch paintings (c. 220 m2) installed in 1916 in the Oslo University Aula in Norway, were approximated from the outdoor air concentrations, indoor to outdoor concentration ratios and dry deposition velocities. The annual deposition of the pollutants to the paintings was found to have been 4–25 times lower than has been reported to buildings outdoors in the urban background in the centre of Oslo. It reflected the outdoor deposition but varied less, from 0.3 to 1.2 g m−2 a−1. The accumulated deposition since 1916, and then not considering the regularly performed cleaning of the paintings, was found to have been 43 ± 13 g m−2, and 110 ± 40 g m−2 in a similar situation since 1835. The ozone deposition, and the PM2.5 deposition before the 1960s, were a relatively larger part of the accumulated total indoor (to the paintings) than reported outdoor deposition. About 18 and 33 times more O3 than NOx and PM2.5 deposition was estimated to the paintings in 2020, as compared to the about similar reported outdoor dry deposition of O3 and NOx. The deposition of PM2.5 to the paintings was probably reduced with about 62% (50–80%) after installation of mechanical filtration in 1975 and was estimated to be 0.011 (± 0.006) g m−2 in 2020.publishedVersio
Copper Oxide Nanoparticles Stimulate the Immune Response and Decrease Antioxidant Defense in Mice After Six-Week Inhalation
Get PDFCopper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.publishedVersio
The colony forming efficiency assay for toxicity testing of nanomaterials – Modifications for higher-throughput
Get PDFTo 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.publishedVersio
Integument carotenoid-based colouration reflects contamination to perfluoroalkyl substances, but not mercury, in arctic black-legged kittiwakes
Get PDFAnthropogenic 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.publishedVersio
Spatial trends of chlorinated paraffins and dechloranes in air and soil in a tropical urban, suburban, and rural environment
Get PDFThere are large knowledge gaps concerning environmental levels and fate of many organic pollutants, particularly for chemicals of emerging concern in tropical regions of the Global South. In this study, we investigated the levels of chlorinated paraffins (CPs) and dechloranes in air and soil in rural, suburban, and urban regions in and around Dar es Salaam, Tanzania. Samples were also collected near the city's main municipal waste dumpsite and an electronic waste (e-waste) handling facility. In passive air samples, short chain CPs (SCCPs) dominated, with an average estimated concentration of 22 ng/m3, while medium chain CPs (MCCPs) had an average estimated concentration of 9 ng/m3. The average estimated air concentration of ∑dechloranes (Dechlorane Plus (DP) + Dechlorane 602 + Dechlorane 603) was three to four orders of magnitudes lower, 2 pg/m3. In soil samples, MCCPs dominated with an average concentration of 640 ng/g dw, followed by SCCPs with an average concentration of 330 ng/g dw, and ∑dechloranes with an average concentration of 0.9 ng/g dw. In both air and soil, DP was the dominating dechlorane compound. Urban pulses were observed for CPs and dechloranes in air and soil. CPs were in addition found in elevated levels at the municipal waste dumpsite and the e-waste handling facility, while DPs were found in elevated levels at the e-waste handling facility. This suggests that waste handling sites represent important emission sources for these pollutants. Investigations into seasonal trends and environmental fate of CPs and dechloranes showed that monsoonal rain patterns play a major role in governing air concentrations and mobility, particularly for the less volatile MCCPs and dechloranes. This study is the first to report levels of CPs in air from sub-Saharan Africa, and DP, Dechlorane 602, and Dechlorane 603 in soil from sub-Saharan Africa.publishedVersio
Numerical Study of Non-Linear Effects for a Swept Bias Langmuir Probe
Get PDFWe present a numerical study disclosing non-linear effects and hysteresis loops for a swept bias Langmuir probe. A full kinetic particle in cell (PIC) model has been used to study the temporal sheath effects and the probe current. Langmuir "close to steady state" condition is required to characterize the plasma. However, during operations above frequencies normally used, capacitive and non-linear resistive effects are being unveiled. We demonstrate how ion and electron density and temperature change properties of the probe-plasma system. We also show that a swept Langmuir probe exhibits essential properties described as the "fingerprint of memristors" and how a Langmuir probe can be identified as a transversal memristor. Understanding non-linear processes might enable new ways to operate Langmuir probes with higher sampling rates and better accuracy.publishedVersio
The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
Get PDFBackground 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/).publishedVersio
Mercury isotope evidence for Arctic summertime re-emission of mercury from the cryosphere
Get PDFDuring Arctic springtime, halogen radicals oxidize atmospheric elemental mercury (Hg0), which deposits to the cryosphere. This is followed by a summertime atmospheric Hg0 peak that is thought to result mostly from terrestrial Hg inputs to the Arctic Ocean, followed by photoreduction and emission to air. The large terrestrial Hg contribution to the Arctic Ocean and global atmosphere has raised concern over the potential release of permafrost Hg, via rivers and coastal erosion, with Arctic warming. Here we investigate Hg isotope variability of Arctic atmospheric, marine, and terrestrial Hg. We observe highly characteristic Hg isotope signatures during the summertime peak that reflect re-emission of Hg deposited to the cryosphere during spring. Air mass back trajectories support a cryospheric Hg emission source but no major terrestrial source. This implies that terrestrial Hg inputs to the Arctic Ocean remain in the marine ecosystem, without substantial loss to the global atmosphere, but with possible effects on food webs.publishedVersio