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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
To assess how climate-sensitive factors may affect the exposure to organochlorines (OCs) and perfluoroalkyl substances (PFASs), we monitored concentrations in eggs of the common goldeneye (Bucephala clangula) over two decades (1999–2019) in central Norway. The goldeneye alternates between marine and freshwater habitats and is sensitive to climate variation, especially due to alterations in ice conditions which may affect feeding conditions. We assessed how biological factors such as diet (stable isotopes δ13C and δ15N), the onset of egg laying, and physical characteristics such as winter climate (North Atlantic Oscillation: NAOw) influenced exposure. We predicted compounds to show different temporal trends depending on whether they were still in production (i.e. some PFASs) or have been banned (i.e. legacy OCs and some PFASs). Therefore, we controlled for potential temporal trends in all analyses. There were declining trends for α- and γ-hexachlorocyclohexane (HCH), oxychlordane, cis-chlordane, cis-nonachlor, p,p′-dichlorodiphenyltrichloroethane (p.p′-DDT) and less persistent polychlorinated biphenyl (PCB) congeners (e.g. PCB101). In contrast, the dominant compounds, such as p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and persistent PCB congeners, were stable, whereas hexachlorobenzene (HCB) increased over time. Most OCs were positively related to δ15N, suggesting higher exposure in birds feeding at upper trophic levels. Chlordanes and HCB were positively associated with δ13C, indicating traces of marine input for these compounds, whereas the relationships to most PCBs were negative. Among PFASs, perfluorooctanesulfonamide (PFOSA) and perfluorohexane sulfonic acid (PFHxS) declined. Most PFASs were positively associated with δ13C, whereas there were no associations with δ15N. Egg laying date was positively associated to perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), suggesting that some of the PFAS load originated from the wintering locations. Although NAOw had little impact on the exposure to organohalogenated contaminants, factors sensitive to climate change, especially diet, were associated with the exposure to OHCs in goldeneyes.
2022
2022
2022
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.
2022
NILU - Norsk Institutt for luftforskning har på oppdrag for Boliden Odda AS, utført sprednings- og avsetningsberegninger i forbindelse med utslipp fra sinkproduksjonsanlegget. Studien beregner luftkonsentrasjon og avsetning av svovel (forsuring) og konsentrasjon av metaller/svevestøv ved dagens sinkproduksjon og ved en planlagt utvidelse. Timesmiddel-, døgnmiddel- og årsmiddel-konsentrasjon av SO2 og PM10 er beregnet til å være innenfor grenseverdier og luftkvalitetskriterier ved dagens og utvidet produksjon. Beregningene viser mulig overskridelse av målsetningsverdien for kadmium ved en utvidelse av produksjonen. Utvidelse i produksjon gir et ytterligere bidrag til overskridelsen av tålegrensen (forsuring) i området rundt Odda. Økningen i avsetning forøvrig er beregnet å være i områder hvor tålegrensen er mer robust. Rapporten er en revisjon av NILU-rapport 3/2019.
NILU
2022
Retrievals of trace gas concentrations from satellite observations are mostly performed for clear regions or regions with low cloud coverage. However, even fully clear pixels can be affected by clouds in the vicinity, either by shadowing or by scattering of radiation from clouds in the clear region. Quantifying the error of retrieved trace gas concentrations due to cloud scattering is a difficult task. One possibility is to generate synthetic data by three-dimensional (3D) radiative transfer simulations using realistic 3D atmospheric input data, including 3D cloud structures. Retrieval algorithms may be applied on the synthetic data, and comparison to the known input trace gas concentrations yields the retrieval error due to cloud scattering.
In this paper we present a comprehensive synthetic dataset which has been generated using the Monte Carlo radiative transfer model MYSTIC (Monte Carlo code for the phYSically correct Tracing of photons In Cloudy atmospheres). The dataset includes simulated spectra in two spectral ranges (400–500 nm and the O2A-band from 755–775 nm). Moreover it includes layer air mass factors (layer-AMFs) calculated at 460 nm. All simulations are performed for a fixed background atmosphere for various sun positions, viewing directions and surface albedos.
Two cloud setups are considered: the first includes simple box clouds with various geometrical and optical thicknesses. This can be used to systematically investigate the sensitivity of the retrieval error on solar zenith angle, surface albedo and cloud parameters. Corresponding 1D simulations are also provided. The second includes realistic three-dimensional clouds from an ICON large eddy simulation (LES) for a region covering Germany and parts of surrounding countries. The scene includes cloud types typical of central Europe such as shallow cumulus, convective cloud cells, cirrus and stratocumulus. This large dataset can be used to quantify the trace gas concentration retrieval error statistically.
Along with the dataset, the impact of horizontal photon transport on reflectance spectra and layer-AMFs is analysed for the box-cloud scenarios. Moreover, the impact of 3D cloud scattering on the NO2 vertical column density (VCD) retrieval is presented for a specific LES case. We find that the retrieval error is largest in cloud shadow regions, where the NO2 VCD is underestimated by more than 20 %.
The dataset is available for the scientific community to assess the behaviour of trace gas retrieval algorithms and cloud correction schemes in cloud conditions with 3D structure.
2022
Per and polyfluoroalkyl substances (PFASs) are found in Antarctic wildlife, with high levels in the avian top predator south polar skua (Catharacta maccormicki). As increasing PFAS concentrations were found in the south polar skua during the breeding season in Antarctica, we hypothesised that available prey during the breeding period contributes significantly to the PFAS contamination in skuas. To test this, we compared PFAS in south polar skuas and their main prey from two breeding sites on opposite sides of the Antarctic continent: Antarctic petrel (Thalassoica antarctica) stomach content, eggs, chicks, and adults from Svarthamaren in Dronning Maud Land and Adélie penguin chicks (Pygoscelis adeliae) from Dumont d’Urville in Adélie Land. Of the 22 PFAS analysed, seven were present in the majority of samples, except petrel stomach content [only perfluoroundecanoate (PFUnA) present] and Adélie penguins (only four compounds present), with increasing concentrations from the prey to the skuas. The biomagnification factors (BMFs) were higher at Dumont d’Urville than Svarthamaren. When adjusted to reflect one trophic level difference, the BMFs at Svarthamaren remained the same, whereas the ones at Dumont d’Urville doubled. At both the colonies, the skua PFAS pattern was dominated by perfluorooctanesulfonic acid (PFOS), followed by PFUnA, but differed with the presence of branched PFOS and perfluorotetradecanoate (PFTeA) and lack of perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) at Dumont d’Urville. At Svarthamaren, the pattern in the prey was comparable to the skuas, but with a higher relative contribution of PFTeA in prey. At Dumont d’Urville, the pattern in the prey differed from the skuas, with the domination of PFUnA and the general lack of PFOS in prey. Even though the PFAS levels are low in Antarctic year-round resident prey, the three lines of evidence (pattern, BMF difference, and BMF adjusted to one trophic level) suggest that the Antarctic petrel are the significant source of PFAS in the Svarthamaren skuas, whereas the skuas in Dumont d’Urville have other important sources to PFAS than Adélie penguin, either in the continent or external on the inter-breeding foraging grounds far from Antarctica.
2022
Background
Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases.
Methods
Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references.
Results
Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles.
Conclusions
The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.
2022
We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, “Nanoparticle Populations” of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
2022
2022
Northern Fulmars (Fulmarus glacialis) are a pelagic seabird species distributed at northern and polar latitudes. They are often used as an indicator of plastic pollution in the North Sea region, but data are lacking from higher latitudes, especially when it comes to chicks. Here, we investigated amounts of ingested plastic and their characteristics in fulmar chicks from the Faroe Islands. Plastic particles (1 mm) in chicks of two age classes were searched using a digestion method with KOH. In addition, to evaluate if additive tissue burden reflects plastic ingestion, we measured liver tissue concentrations of two pollutant classes associated with plastic materials: polybrominated diphenyl ethers (PBDEs) and several dechloranes, using gas chromatography with high-resolution mass spectrometry. The most common shape was hard fragment (81%) and the most common polymer was polyethylene (73%). Plastic contamination did not differ between either age class, and we found no correlation between neither the amount and mass of plastic particles and the concentration of additives. After comparison with previous studies on adult fulmars, we do not recommend using chicks for biomonitoring adults because chicks seem to ingest more plastics than adults.
2022
2022
Prøvetaking av PM10 i omgivelsene til Brevik bru. 22. sept – 5. okt 2021.
NILU – Norsk institutt for luftforskning har, på oppdrag fra Statens vegvesen – Drift og vedlikehold sør, utført prøvetaking av PM10 i luft i omgivelsene til Brevik bru mellom Brevik og Stathelle. Målingene ble utført med filterprøvetakere ved 2 steder nedvinds for brua i forhold til lokale hovedvindretninger. Prøvene ble tatt hver dag i perioden 22. september – 5. oktober 2021 for å utrede i hvilken grad prosjekt Brevik bru påfører lokalt miljø støvforurensning som kan medføre helseplager. 18 av de 28 prøvene tatt ble analysert med hensyn på metaller.
Det ble ikke funnet sammenheng mellom konsentrasjonsforskjell mellom de to målestedene og vindretning mot et av stedene for de målte komponentene. PM10- og metallkonsentrasjoner var godt under grense-/målsettingsverdier.
NILU
2022
2022
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
VKM has performed a risk-benefit assessment of sunscreen use and six UV filters. This task
was undertaken on the initiative of a VKM Panel in response to the apparent paradox
between the need for protective measures, such as use of sunscreens, to reduce Norway’s
high incidence and mortality of skin cancer and a consumer concern for the safety of
sunscreens. Concerns include safety of ingredients and sunscreens’ effect on vitamin D
synthesis. Sunscreen products are legally regulated as cosmetic products in the EU, and only
approved UV filters up to a maximum determined concentration are allowed in the ready-foruse preparation.
VKM used a systematic approach to assess risks and benefits of sunscreen use and risks of
six selected UV filters: bis-ethyl-hexyloxyphenol methoxyphenyl triazine (BEMT), butyl
methoxydibenzoyl methane (BMDBM), 2-ethylhexyl salicylate (EHS), ethylhexyl triazone
(EHT), octocrylene (OC), and titanium dioxide in nanoform (NP-TiO2). These UV filters are
among the most frequently used in sunscreens on the Norwegian market. Sunscreen sprays
and lip products were not included. Scientific publications and reports up to 2020 were
retrieved to assess adverse and protective effects of sunscreen and adverse effects of UV
filters. We assessed risk of bias in the studies and evidence for health outcomes with the aid
of validity tools, and estimated exposure to each UV filter using probabilistic methods.
The evidence showed that sunscreens were beneficial in protecting against certain skin
cancers. Insufficient evidence precluded determination of the hazard associated with
sunscreen use.
The UV filters occurred in concentrations similar to or below the limits set in the EU
cosmetics regulative. VKM considered that little to no hazard was associated with use of the
six evaluated UV filters.
VKM concludes that the risks related to use of the six evaluated UV filters are negligible since
the real-life use of these UV filters is several-fold lower than the amounts that may cause
any adverse health effect. The evidence for harmful health effects of sunscreens is
insufficient to determine risk. Sunscreen use protects against certain skin cancers and is
beneficial for the general Norwegian population.
2022
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