Found 2678 publications. Showing page 44 of 268:
Thymidine Kinase+/− Mammalian Cell Mutagenicity Assays for Assessment of Nanomaterials
The methods outlined here are part of a series of papers designed specifically for genotoxicity assessment of nanomaterials (NM). Common Considerations such as NM characterization, sample preparation and dose selection, relevant to all genotoxicity assays, are found in an accompanying paper. The present paper describes methods for evaluation of mutagenicity in the mammalian (mouse) thymidine kinase (Tk) gene occurring in L5178Y mouse lymphoma (ML) cells and in the designated TK gene in human lymphoblastoid TK6 cells. Mutations change the functional genotype from TK+/− to TK−/−, detectable as cells surviving on media selective for the lack of thymidine kinase (TK) function. Unlike cells with TK enzyme function, the TK−/− cells are unable to integrate the toxic selection agent, allowing these cells to survive as rare mutant colonies. The ML assay has been shown to detect a broad spectrum of genetic damage, including both small scale (point) mutations and chromosomal alterations. This assay is a widely used mammalian cell gene mutation assay for regulatory purposes and is included in the core battery of genotoxicity tests for regulatory decision-making. The TK6 assay is an assay using a human cell line derived similarly via mutagenic manipulations and optimal selection. Details are provided on the materials required, cell culture methods, selection of test chemical concentrations, cytotoxicity, treatment time, mutation expression, cloning, and data calculation and interpretation. The methods describe the microwell plate version of the assays without metabolic activation.
2022
The alamar blue assay in the context of safety testing of nanomaterials
The Alamar Blue (AB) assay is widely used to investigate cytotoxicity, cell proliferation and cellular metabolic activity within different fields of toxicology. The use of the assay with nanomaterials (NMs) entails specific aspects including the potential interference of NMs with the test. The procedure of the AB assay applied for testing NMs is described in detail and step-by-step, from NM preparation, cell exposure, inclusion of interference controls, to the analysis and interpretation of the results. Provided that the proper procedure is followed, and relevant controls are included, the AB assay is a reliable and high throughput test to evaluate the cytotoxicity/proliferation/metabolic response of cells exposed to NMs.
2022
In vivo Mammalian Alkaline Comet Assay: Method Adapted for Genotoxicity Assessment of Nanomaterials
The in vivo Comet assay measures the generation of DNA strand breaks under conditions in which the DNA will unwind and migrate to the anode in an electrophoresis assay, producing comet-like figures. Measurements are on single cells, which allows the sampling of a diversity of cells and tissues for DNA damaging effects. The Comet assay is the most common in vivo method for genotoxicity assessment of nanomaterials (NM). The Method outlined here includes a recommended step-by-step approach, consistent with OECD 489, taking into consideration the issues impacting assessment of NM, including choice of cells or systems, handling of NM test articles, dose determination, assay methods and data assessment. This method is designed to be used along with the accompanying “Common Considerations” paper, which discusses issues common to any genotoxicity assay using NM as a test article.
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Fourteen legacy organochlorine (OC) contaminants and 12 perfluoroalkyl substances (PFASs) were measured in eggs of tawny owls (Strix alueco) in central Norway (1986–2019). We expected OCs to have reached stable equilibrium levels due to bans, and that recent phase-out of some PFASs would have slowed the increase of these compounds. ∑OC comprised on average approximately 92% of the measured compounds, whereas ∑PFAS accounted for approximately 8%. However, whereas the ∑OC to ∑PFAS ratio was approximately 60 in the first 5 years of the study, it was only approximately 11 in the last 5 years. Both OC pesticides and polychlorinated biphenyls (PCBs) showed substantial declines over the study period (~85%–98%): hexachlorocyclohexanes and chlordanes seemed to be levelling off, whereas p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and hexachlororbenzene (HCB), and most PCB congeners still seemed to decline at a more or less constant rate. While the concentration of perfluorooctane sulfonic acid (PFOS), the dominating PFAS, was reduced by approximately 43%, other perfluorinated sulfonates (PFSAs) showed only minor changes. Moreover, the median concentrations of seven perfluorinated carboxylic acids (PFCAs) increased approximately five-fold over the study period. Perfluorononanoic acid and perfluoroundecanoate acid, however, seemed to be levelling off in recent years. In contrast, perfluorododecanoic acid, perfluorodecanoate acid, perfluorotridecanoic acid, and perfluorotetradecanoic acid seemed to increase more or less linearily. Finally, perfluorooctanoic acid (PFOA) was increasingly likely to be detected over the study period. Hence, most legacy OCs and PFOS have not reached a lower threshold with stable background levels, and voluntary elimination of perfluoroalkyl carboxylates still has not resulted in declining levels in tawny owls in central Norway.
2022
Insight into processes determining the exposure of organohalogenated contaminants (OHCs) in wildlife might be gained from comparing predators in different ecosystems. This study compared two avian predator species with similar food chain lengths: the goldeneye duck (Bucephala clangula) and the tawny owl (Strix aluco) breeding in adjacent freshwater- and terrestrial ecosystems in central Norway. We measured lipophilic organochlorines (OCs) and protein-bound perfluorinated substances (PFASs) in eggs of the two species over 21 years (1999–2019). Across years, the proportional distribution of OCs (∼90% of the ΣOHC load) relative to PFASs (∼10%) was similar in the two species. Moreover, ΣOC concentrations were similar between the species, but PFAS compounds were 2–12 times higher in the goldeneyes than in tawny owls. OC-pesticides dominated in tawny owls (∼60% of ΣOC), whereas persistent polychlorinated biphenyl (PCBs) congeners were the main OC components in goldeneyes (∼70% of ΣOC). The lipid-normalized concentrations of most OC-pesticides and the less persistent PCB101 declined significantly in both species. Hexachlorobenzene (HCB), p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), and more persistent PCBs decreased in tawny owls, while they tended to increase in goldeneyes. The increase in HCB was particulary robust. Among the PFASs, contrasted temporal trends were found across the species for four out of 11 compounds: PFOS declined while most perfluorocarboxylic acids (PFCAs) increased in tawny owls. In contrast, most PFASs were stable in goldeneyes. Moreover, there was no annual covariance between the OHC exposure in the two species: i.e., high concentrations in one species in a given year did not translate into high concentrations in the other. Hence, the two avian predators in adjacent ecosystems seem to be subject to different processes determining the OHC exposure, probably related to variation in diet and climate, long-range transport of different contaminants, and emissions of pollution locally.
2022
Three-dimensional (3D) cloud structures may impact atmospheric trace gas products from ultraviolet–visible (UV–Vis) sounders. We used synthetic and observational data to identify and quantify possible cloud-related bias in NO2 tropospheric vertical column density (TVCD). The synthetic data were based on high-resolution large eddy simulations which were input to a 3D radiative transfer model. The simulated visible spectra for low-earth-orbiting and geostationary geometries were analysed with standard retrieval methods and cloud correction schemes that are employed in operational NO2 satellite products. For the observational data, the NO2 products from the TROPOspheric Monitoring Instrument (TROPOMI) were used, while the Visible Infrared Imaging Radiometer Suite (VIIRS) provided high-spatial-resolution cloud and radiance data. NO2 profile shape, cloud shadow fraction, cloud top height, cloud optical depth, and solar zenith and viewing angles were identified as the metrics being the most important in identifying 3D cloud impacts on NO2 TVCD retrievals. For a solar zenith angle less than about 40∘ the synthetic data show that the NO2 TVCD bias is typically below 10 %, while for larger solar zenith angles the NO2 TVCD is low-biased by tens of percent. The horizontal variability of NO2 and differences in TROPOMI and VIIRS overpass times make it challenging to identify a similar bias in the observational data. However, for optically thick clouds above 3000 m, a low bias appears to be present in the observational data.
2022
An actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry
Omics-based technologies have enabled comprehensive characterization of our exposure to environmental chemicals (chemical exposome) as well as assessment of the corresponding biological responses at the molecular level (eg, metabolome, lipidome, proteome, and genome). By systematically measuring personal exposures and linking these stimuli to biological perturbations, researchers can determine specific chemical exposures of concern, identify mechanisms and biomarkers of toxicity, and design interventions to reduce exposures. However, further advancement of metabolomics and exposomics approaches is limited by a lack of standardization and approaches for assigning confidence to chemical annotations. While a wealth of chemical data is generated by gas chromatography high-resolution mass spectrometry (GC-HRMS), incorporating GC-HRMS data into an annotation framework and communicating confidence in these assignments is challenging. It is essential to be able to compare chemical data for exposomics studies across platforms to build upon prior knowledge and advance the technology. Here, we discuss the major pieces of evidence provided by common GC-HRMS workflows, including retention time and retention index, electron ionization, positive chemical ionization, electron capture negative ionization, and atmospheric pressure chemical ionization spectral matching, molecular ion, accurate mass, isotopic patterns, database occurrence, and occurrence in blanks. We then provide a qualitative framework for incorporating these various lines of evidence for communicating confidence in GC-HRMS data by adapting the Schymanski scoring schema developed for reporting confidence levels by liquid chromatography HRMS (LC-HRMS). Validation of our framework is presented using standards spiked in plasma, and confident annotations in outdoor and indoor air samples, showing a false-positive rate of 12% for suspect screening for chemical identifications assigned as Level 2 (when structurally similar isomers are not considered false positives). This framework is easily adaptable to various workflows and provides a concise means to communicate confidence in annotations. Further validation, refinements, and adoption of this framework will ideally lead to harmonization across the field, helping to improve the quality and interpretability of compound annotations obtained in GC-HRMS.
2022
Is Glacial Meltwater a Secondary Source of Legacy Contaminants to Arctic Coastal Food Webs?
Climate change-driven increases in air and sea temperatures are rapidly thawing the Arctic cryosphere with potential for remobilization and accumulation of legacy persistent organic pollutants (POPs) in adjacent coastal food webs. Here, we present concentrations of selected POPs in zooplankton (spatially and seasonally), as well as zoobenthos and sculpin (spatially) from Isfjorden, Svalbard. Herbivorous zooplankton contaminant concentrations were highest in May [e.g., ∑polychlorinated biphenyls (8PCB); 4.43, 95% CI: 2.72–6.3 ng/g lipid weight], coinciding with the final stages of the spring phytoplankton bloom, and lowest in August (∑8PCB; 1.6, 95% CI: 1.29–1.92 ng/g lipid weight) when zooplankton lipid content was highest, and the fjord was heavily impacted by sediment-laden terrestrial inputs. Slightly increasing concentrations of α-hexachlorocyclohexane (α-HCH) in zooplankton from June (1.18, 95% CI: 1.06–1.29 ng/g lipid weight) to August (1.57, 95% CI: 1.44–1.71 ng/g lipid weight), alongside a higher percentage of α-HCH enantiomeric fractions closer to racemic ranges, indicate that glacial meltwater is a secondary source of α-HCH to fjord zooplankton in late summer. Except for α-HCH, terrestrial inputs were generally associated with reduced POP concentrations in zooplankton, suggesting that increased glacial melt is not likely to significantly increase exposure of legacy POPs in coastal fauna.
2022