Publications by authors named "Nico van den Brink"

52 Publications

Determination of 56 per- and polyfluoroalkyl substances in top predators and their prey from Northern Europe by LC-MS/MS.

Chemosphere 2021 Aug 10;287(Pt 2):131775. Epub 2021 Aug 10.

National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece. Electronic address:

Per- and polyfluoroalkyl substances (PFAS) are a group of emerging substances that have proved to be persistent and highly bioaccumulative. They are broadly used in various applications and are known for their long-distance migration and toxicity. In this study, 65 recent specimens of a terrestrial apex predator (Common buzzard), freshwater and marine apex predators (Eurasian otter, harbour porpoise, grey seal, harbour seal) and their potential prey (bream, roach, herring, eelpout) from northern Europe (United Kingdom, Germany, the Netherlands and Sweden) were analyzed for the presence of legacy and emerging PFAS, employing a highly sensitive liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method. 56 compounds from 14 classes were measured; 13 perfluoroalkyl carboxylic acids (PFCAs), 7 perfluoroalkyl sulphonic acids (PFSAs), 3 perfluorooctane sulfonamides (FOSAs), 4 perfluoroalkylphosphonic acids (PFAPAs), 3 perfluoroalkylphosphinic acids (PFPi's), 5 telomer alcohols (FTOHs), 2 mono-substituted polyfluorinated phosphate esters (PAPs), 2 di-substituted polyfluorinated phosphate esters (diPAPs), 6 saturated fluorotelomer acids (FTAS), 3 unsaturated fluorotelomer acids (FTUAs), 2 N-Alkyl perfluorooctane sulfonamidoethanols (FOSEs), 3 fluorotelomer sulphonic acids (FTSAs), 2 perfluoroether carboxylic acids (PFECAs) and 1 chlorinated perfluoroether sulphonic acid (Cl-PFESA). All samples were lyophilized before analysis, in order to enhance extraction efficiency, improve the precision and achieve lower detection limits. The analytes were extracted from the dry matrices through generic methods of extraction, using an accelerated solvent extraction (ASE), followed by clean-up through solid phase extraction (SPE). Method detection limits and method quantification limits ranged from 0.02 to 1.25 ng/g wet weight (ww) and from 0.05 to 3.79 ng/g (ww), respectively. Recovery ranged from 40 to 137%. Method precision ranged from 3 to 20 %RSD. The sum of PFAS concentration in apex predators livers ranged from 0.2 to 20.2 μg/g (ww), whereas in the fish species muscle tissues it ranged from 16 to 325 ng/g (ww). All analyzed specimens were primarily contaminated with PFOS, while the three PFPi's included in this study exhibited frequency of appearance (FoA) 100 %. C9 to C13 PFCAs were found at high concentrations in apex predator livers, while the overall PFAS levels in fish fillets also exceeded ecotoxicological thresholds. The findings of our study show a clear association between the PFAS concentrations in apex predators and the geographical origin of the specimens, with samples that were collected in urban and agricultural zones being highly contaminated compared to samples from pristine or semi-pristine areas. The high variety of PFAS and the different PFAS composition in the apex predators and their prey (AP&P) samples is alarming and strengthens the importance of PFAS monitoring across the food chain.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131775DOI Listing
August 2021

Environmental exposure to cadmium reduces the primary antibody-mediated response of wood mice (Apodemus sylvaticus) from differentially polluted locations in the Netherlands.

Environ Pollut 2021 Aug 5;289:117909. Epub 2021 Aug 5.

Sub-department of Toxicology, Wageningen University, Netherlands. Electronic address:

The Wood mouse (Apodemus sylvaticus) is a widespread mammalian species that acts as a reservoir host for multiple infections, including zoonotic diseases. Exposure to immunotoxins, like for instance trace metals, may reduce the ability of the host to mount proper responses to pathogens, potentially increasing the transmission and prevalence of infections. Antibody-mediated responses are crucial in preventing and limiting infections, and the quantification of the primary antibody response is considered a sensitive predictor of immunosuppression. The current study aims to investigate effects of cadmium exposure on the antibody-mediated responses of wood mice inhabiting polluted and non-polluted areas in the Netherlands. Wood mice were captured alive at different locations and immunized to sheep red blood cells (SRBC) to induce a primary antibody response. SRBC-specific antibody-producing cells, or plaque forming cells (PFC), were quantified and related to kidney cadmium levels. Differential circulating main leukocyte populations were also characterised. Cadmium concentrations in mice kidneys differed between mice captured at different locations, and increased with individual body mass, likely associated with age-related time of exposure. Effect of cadmium was apparent on the percentages of B cell counts in blood. Because of potential natural immune heterogeneity between wild rodent populations, mice immune responses were analysed and compared grouped by captured locations. Capture location had significant effect on the total counts of white blood cells. Increasing cadmium exposure in wood mice captured from polluted sites was associated with a decrease of splenic PFC counts. This field research shows that wood mice antibody responses can be impaired by cadmium exposure, even at low environmental levels, by affecting B cell functioning mainly. Impaired B cell function can make exposed mice more susceptible to infections, potentially increasing the reservoir function of their populations. It also shows that immunomodulatory effects in the field should be assessed site specifically.
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http://dx.doi.org/10.1016/j.envpol.2021.117909DOI Listing
August 2021

Modulatory Effects of Mercury (II) Chloride (HgCl ) on Chicken Macrophage and B-Lymphocyte Cell Lines with Viral-Like Challenges In Vitro.

Environ Toxicol Chem 2021 Jul 20. Epub 2021 Jul 20.

Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands.

Mercury (Hg) is a toxic trace metal ubiquitously distributed in the environment. Inorganic mercury (as HgCl ) can cause immunotoxicity in birds, but the mechanisms of action are still not fully resolved, especially with respect to responses to viral infections. To investigate the potential immunomodulatory effects of Hg on specific cell types of the avian immune system, chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines were applied as in vitro models for the innate and adaptive immune systems, respectively. The cells were stimulated with synthetic double-stranded RNA, which can be recognized by toll-like receptor-3 to mimic a viral infection. The Hg showed concentration-dependent cytotoxicity in both cell lines, with similar median effect concentrations at 30 µM. The cytotoxicity of Hg was closely related to glutathione (GSH) depletion and reactive oxygen species induction, whereas the de novo synthesis of GSH acted as a primary protective strategy. Nitric oxide produced by activated macrophages was strongly inhibited by Hg , and was also influenced by cellular GSH levels. Cell proliferation, gene expression of microRNA-155, and cellular IgM levels in B cells were decreased at noncytotoxic Hg concentrations. The secretion of antiviral interferon-α was induced by Hg in both cell lines. Overall, our results suggest that Hg exposure can cause immunomodulatory effects in birds by disrupting immune cell proliferation and cytokine production, and might result in disorders of the avian immune system. Environ Toxicol Chem 2021;00:1-12. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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http://dx.doi.org/10.1002/etc.5169DOI Listing
July 2021

Are long-term exposure studies needed? Short-term toxicokinetic model predicts the uptake of metal nanoparticles in earthworms after nine months.

Ecotoxicol Environ Saf 2021 Sep 27;220:112371. Epub 2021 May 27.

Division of Toxicology, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands.

Uptake of most metal nanoparticles (NPs) in organisms is assumed to be mainly driven by the bioavailability of the released ions, as has been verified in controlled and short-term exposure tests. However, the changeability of NPs and the dynamic processes which NPs undergo in the soil environment, bring uncertainty regarding their interactions with soil organisms over a long period of time. To assess the potential impacts of long-term exposure scenarios on the toxicokinetic of metal NPs, earthworms Eisenia fetida were exposed to soils spiked with pristine Ag-NP, aged Ag-NP (AgS-NP) and ionic Ag for nine months, and results were compared to those from a similar short-term (28 days) experiment, conducted under similar conditions. Overall, there were no statistical differences between long-term accumulation patterns in earthworms exposed to pristine Ag-NP and AgNO, while for AgS-NP, the amount of Ag internalized after 9 months was five times lower than for the other treatments. Average Ag concentrations in soil pore water in all treatments did not change over time, however the soil pH decreased and electrical conductivity increased in all treatments. Metallothionein concentrations in exposed earthworms were not statistically different from levels in untreated earthworms. Finally, the short-term toxicokinetic models predicted the bioaccumulation in earthworms exposed to Ag-NP, AgNO after nine months on the whole. Although the bioaccumulation for AgS-NPs was somewhat under-predicted, the rate of accumulation of AgS-NPs is much lower than that of Ag-NPs or AgNO and thus potentially of lower concern. Nevertheless, better understanding about the exposure kinetics of AgS-NP would help to address potential nano-specific toxicokinetic and toxicodynamics, also of other sulfidized metal NPs.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112371DOI Listing
September 2021

The toxicity and toxicokinetics of imidacloprid and a bioactive metabolite to two aquatic arthropod species.

Aquat Toxicol 2021 Jun 11;235:105837. Epub 2021 Apr 11.

Aquatic Ecology and Water Quality Management group, Wageningen University, P.O. Box 47, 6700 AA Wageningen, the Netherlands; Wageningen Environmental Research, P.O. Box 47, 6700 AA Wageningen, the Netherlands.

Previous studies have explored effects of imidacloprid and its metabolites on terrestrial species, such as bees, and indicated the importance of some active metabolites. However, the biotransformation of IMI and the toxicity of its metabolites to aquatic arthropods are largely unknown, especially the mechanisms driving species sensitivity differences and time-cumulative toxicity effects. To assess the potential effects of the metabolization of IMI and the toxicokinetics and toxicity of the metabolite(s) on aquatic arthropods, we first studied the acute toxicity of IMI and relevant metabolites to the mayfly species Cloen dipterum (sensitive to IMI) and the amphipod species Gammarus pulex (less sensitive to IMI). Secondly, toxicokinetic experiments were conducted using both the parent compound and imidacloprid-olefin (IMI-ole), a metabolite assessed as toxic in the acute tests and defined as bioactive. Of the four tested metabolites, only IMI-ole was readily biotransformed from the parent IMI and showed similar toxicity to C. dipterum as IMI. However, C. dipterum was hardly able to eliminate IMI-ole from its body. For G. pulex, IMI-ole was also the only detected metabolite causing toxicity, but the biotransformation of IMI to IMI-ole was slower and lower in G. pulex compared to C. dipterum, and G. pulex eliminated IMI-ole quicker than C. dipterum. Our results on internal kinetics of IMI and IMI-ole, and on biotransformation of IMI indicated that the metabolite IMI-ole was toxic and was rather persistent inside the body tissue of both invertebrate species, especially for C. dipterum. In conclusion, as IMI and IMI-ole have similar toxicity and IMI was replaced rapidly by IMI-ole which in turn was poorly eliminated by C. dipterum, the overall toxicity is a function of dose and time. As a result, no long-term threshold of effects of IMI may exist for C. dipterum as the poor elimination results in an ongoing increase of toxicity over time for mayflies as also found experimentally in previous published papers.
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http://dx.doi.org/10.1016/j.aquatox.2021.105837DOI Listing
June 2021

Key principles and operational practices for improved nanotechnology environmental exposure assessment.

Nat Nanotechnol 2020 09 17;15(9):731-742. Epub 2020 Aug 17.

UK Centre for Ecology and Hydrology, Wallingford, Oxfordshire, UK.

Nanotechnology is identified as a key enabling technology due to its potential to contribute to economic growth and societal well-being across industrial sectors. Sustainable nanotechnology requires a scientifically based and proportionate risk governance structure to support innovation, including a robust framework for environmental risk assessment (ERA) that ideally builds on methods established for conventional chemicals to ensure alignment and avoid duplication. Exposure assessment developed as a tiered approach is equally beneficial to nano-specific ERA as for other classes of chemicals. Here we present the developing knowledge, practical considerations and key principles need to support exposure assessment for engineered nanomaterials for regulatory and research applications.
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http://dx.doi.org/10.1038/s41565-020-0742-1DOI Listing
September 2020

A schematic sampling protocol for contaminant monitoring in raptors.

Ambio 2021 Jan 12;50(1):95-100. Epub 2020 May 12.

Area of Toxicology, Faculty of Veterinary Medicine, University of Murcia, Campus Espinardo, 30100, Murcia, Spain.

Birds of prey, owls and falcons are widely used as sentinel species in raptor biomonitoring programmes. A major current challenge is to facilitate large-scale biomonitoring by coordinating contaminant monitoring activities and by building capacity across countries. This requires sharing, dissemination and adoption of best practices addressed by the Networking Programme Research and Monitoring for and with Raptors in Europe (EURAPMON) and now being advanced by the ongoing international COST Action European Raptor Biomonitoring Facility. The present perspective introduces a schematic sampling protocol for contaminant monitoring in raptors. We provide guidance on sample collection with a view to increasing sampling capacity across countries, ensuring appropriate quality of samples and facilitating harmonization of procedures to maximize the reliability, comparability and interoperability of data. The here presented protocol can be used by professionals and volunteers as a standard guide to ensure harmonised sampling methods for contaminant monitoring in raptors.
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http://dx.doi.org/10.1007/s13280-020-01341-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708607PMC
January 2021

Implications of Trophic Variability for Modeling Biomagnification of POPs in Marine Food Webs in the Svalbard Archipelago.

Environ Sci Technol 2020 04 13;54(7):4026-4035. Epub 2020 Mar 13.

Department of Environmental Science, Institute for Wetland and Water Research, Faculty of Science, Radboud University, P.O. Box 9010, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

The occurrence of persistent organic pollutants (POPs) in the Arctic has been of constant concern, as these chemicals cause reproductive effects and mortality in organisms. The Arctic acts as a chemical sink, which makes this system an interesting case for bioaccumulation studies. However, as conducting empirical studies for all Arctic species and POPs individually is unfeasible, methods have been developed. Existing bioaccumulation models are predominately validated for temperate food chains, and do not account for a large variation in trophic levels. This study applies Monte Carlo simulations to account for variability in trophic ecology on Svalbard when predicting bioaccumulation of POPs using the optimal modeling for ecotoxicological applications (OMEGA) bioaccumulation model. Trophic magnification factors (TMFs) were calculated accordingly. Comparing our model results with monitored POP residues in biota revealed that, on average, all predictions fell within a factor 6 of the monitored POP residues in biota. Trophic variability did not affect model performance tremendously, with up to a 25% variability in performance metrics. To our knowledge, we were the first to include trophic variability in predicting biomagnification in Arctic ecosystems using a mechanistic biomagnification model. However, considerable amounts of data are required to quantify the implications of trophic variability on biomagnification of POPs in Arctic food webs.
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http://dx.doi.org/10.1021/acs.est.9b06666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144221PMC
April 2020

Modulatory Effects of Pb on Virally Challenged Chicken Macrophage (HD-11) and B-Lymphocyte (DT40) Cell Lines In Vitro.

Environ Toxicol Chem 2020 05 31;39(5):1060-1070. Epub 2020 Mar 31.

Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands.

Elevated levels of lead have been found in waterfowl, due to human activities. Lead may cause immunomodulatory effects, but the mechanisms are largely unknown, especially after viral challenges. To characterize avian immunomodulatory hazards of lead (Pb) , we used chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines, as in vitro models for the innate and adaptive immune systems, respectively. The cells were activated via toll-like receptor-3 by polyinosinic-polycytidylic acid sodium salt (poly I:C), mimicking viral infections. Our results indicate that Pb is cytotoxic to both cell lines, macrophages being more sensitive. De novo synthesis of glutathione plays an important role in protecting macrophages from Pb intoxication, which might also be closely involved in the induction of nitric oxide after Pb exposure. Stimulatory effects on cell proliferation were noticed at noncytotoxic Pb concentrations as well. Exposure to Pb could also affect the inflammatory status by inhibiting the pro-inflammatory interferon (IFN)-γ while promoting the production of anti-inflammatory type I IFNs in both macrophages and B-cells, and increasing intracellular IgM levels in B-cells. These results suggest that the immunomodulatory effects of Pb in birds are probably closely associated with disruption of immune cell proliferation and cytokine production, potentially causing disorders of the avian immune system. Environ Toxicol Chem 2020;39:1060-1070. © 2020 SETAC.
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http://dx.doi.org/10.1002/etc.4702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277059PMC
May 2020

Legacy and Emerging Persistent Organic Pollutants in Antarctic Benthic Invertebrates near Rothera Point, Western Antarctic Peninsula.

Environ Sci Technol 2020 03 14;54(5):2763-2771. Epub 2020 Feb 14.

Sub-Department of Toxicology, Wageningen University, PO Box 8000, NL 6700 EA Wageningen, the Netherlands.

Pollutant levels in polar regions are gaining progressively more attention from the scientific community. This is especially so for pollutants that persist in the environment and can reach polar latitudes via a wide range of routes, such as some persistent organic pollutants (POPs). In this study, samples of Antarctic marine benthic organisms were analyzed for legacy and emerging POPs (polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides) to comprehensively assess their current POP concentrations and infer the potential sources of the pollutants. Specimens of five benthic invertebrate species were collected at two distinct locations near Rothera research station on the Antarctic Peninsula (67°35'8 ̋ S and 68°7'59 ̋ W). Any impact of the nearby Rothera station as a local source of pollution appeared to be negligible. The most abundant chemicals detected were hexachlorobenzene (HCB) and BDE-209. The highest concentrations detected were in limpets and sea urchins, followed by sea stars, ascidians, and sea cucumbers. The relative congener patterns of PCBs and PBDEs were similar in all of the species. Some chemicals (e.g., heptachlor, oxychlordane, and mirex) were detected in the Antarctic invertebrates for the first time. Statistical analyses revealed that the distribution of the POPs was not only driven by the feeding traits of the species but also by the physicochemical properties of the specific compounds.
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http://dx.doi.org/10.1021/acs.est.9b06622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057541PMC
March 2020

Strategies for robust and accurate experimental approaches to quantify nanomaterial bioaccumulation across a broad range of organisms.

Environ Sci Nano 2019 ;6

Bren School of Environmental Science and Management, Earth Research Institute and University of California Center for the Environmental Implications of Nanotechnology (UC CEIN), University of California, Santa Barbara, California 93106, United States.

One of the key components for environmental risk assessment of engineered nanomaterials (ENMs) is data on bioaccumulation potential. Accurately measuring bioaccumulation can be critical for regulatory decision making regarding material hazard and risk, and for understanding the mechanism of toxicity. This perspective provides expert guidance for performing ENM bioaccumulation measurements across a broad range of test organisms and species. To accomplish this aim, we critically evaluated ENM bioaccumulation within three categories of organisms: single-celled species, multicellular species excluding plants, and multicellular plants. For aqueous exposures of suspended single-celled and small multicellular species, it is critical to perform a robust procedure to separate suspended ENMs and small organisms to avoid overestimating bioaccumulation. For many multicellular organisms, it is essential to differentiate between the ENMs adsorbed to external surfaces or in the digestive tract and the amount absorbed across epithelial tissues. For multicellular plants, key considerations include how exposure route and the role of the rhizosphere may affect the quantitative measurement of uptake, and that the efficiency of washing procedures to remove loosely attached ENMs to the roots is not well understood. Within each organism category, case studies are provided to illustrate key methodological considerations for conducting robust bioaccumulation experiments for different species within each major group. The full scope of ENM bioaccumulation measurements and interpretations are discussed including conducting the organism exposure, separating organisms from the ENMs in the test media after exposure, analytical methods to quantify ENMs in the tissues or cells, and modeling the ENM bioaccumulation results. One key finding to improve bioaccumulation measurements was the critical need for further analytical method development to identify and quantify ENMs in complex matrices. Overall, the discussion, suggestions, and case studies described herein will help improve the robustness of ENM bioaccumulation studies.
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http://dx.doi.org/10.1039/C8EN01378KDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774209PMC
January 2019

Bioturbation of AgS-NPs in soil columns by earthworms.

Environ Pollut 2019 Sep 22;252(Pt A):155-162. Epub 2019 May 22.

Division of Toxicology, Wageningen University & Research, P.O. Box 8000, 6700 EA, Wageningen, the Netherlands.

Sewage sludge contains AgS-NPs causing NP exposure of soil fauna when sludge is applied as soil amendment. Earthworm bioturbation is an important process affecting many soil functions. Bioturbation may be affected by the presence of AgS-NPs, but the earthworm activity itself may also influence the displacement of these NPs that otherwise show little transport in the soil. The aim of this study was to determine effects of AgS-NPs on earthworm bioturbation and effect of this bioturbation on the vertical distribution of AgS-NPs. Columns (12 cm) of a sandy loamy soil with and without Lumbricus rubellus were prepared with and without 10 mg Ag kg, applied as AgS-NPs in the top 2 cm of the soil, while artificial rainwater was applied at ∼1.2 mm day. The soil columns were sampled at three depths weekly for 28 days and leachate collected from the bottom. Total Ag measurements showed more displacement of Ag to deeper soil layers in the columns with earthworms. The application of rain only did not significantly affect Ag transport in the soil. No Ag was detected in column leachates. X-ray tomography showed that changes in macro porosity and pore size distribution as a result of bioturbation were not different between columns with and without AgS-NPs. Earthworm activity was therefore not affected by AgS-NPs at the used exposure concentration. Ag concentrations along the columns and the earthworm density allowed the calculation of the bioturbation rate. The effect on the Ag transport in the soil shows that earthworm burrowing activity is a relevant process that must be taken into account when studying the fate of nanoparticles in soils.
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http://dx.doi.org/10.1016/j.envpol.2019.05.106DOI Listing
September 2019

Stress behaviour and physiology of developing Arctic barnacle goslings ( Branta leucopsis) is affected by legacy trace contaminants.

Proc Biol Sci 2018 Dec;285(1893):20181866

1 Behavioural and Physiological Ecology, Groningen Institute for Evolutionary Life Sciences, University of Groningen , 9747 AG Groningen , The Netherlands.

Natural populations are persistently exposed to environmental pollution, which may adversely impact animal physiology and behaviour and even compromise survival. Responding appropriately to any stressor ultimately might tip the scales for survival, as mistimed behaviour and inadequate physiological responses may be detrimental. Yet effects of legacy contamination on immediate physiological and behavioural stress coping abilities during acute stress are virtually unknown. Here, we assessed these effects in barnacle goslings ( Branta leucopsis) at a historical coal mine site in the Arctic. For three weeks we led human-imprinted goslings, collected from nests in unpolluted areas, to feed in an abandoned coal mining area, where they were exposed to trace metals. As control we led their siblings to feed on clean grounds. After submitting both groups to three well-established stress tests (group isolation, individual isolation, on-back restraint), control goslings behaved calmer and excreted lower levels of corticosterone metabolites. Thus, legacy contamination may decisively change stress physiology and behaviour in long-lived vertebrates exposed at a young age.
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http://dx.doi.org/10.1098/rspb.2018.1866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304058PMC
December 2018

Cell-specific immune-modulation of cadmium on murine macrophages and mast cell lines in vitro.

J Appl Toxicol 2019 07 3;39(7):992-1001. Epub 2019 Mar 3.

Division of Toxicology, Wageningen University and Research, Stippeneng 4, 6708WE, Wageningen, The Netherlands.

Toxic trace metals are widespread contaminants that are potentially immunotoxic even at environmentally low exposure levels. They can modulate the immunity to infections, e.g., in wildlife species living in contaminated areas. The diverse immune cell types can be differentially affected by the exposure leading to the modulation of specific protective mechanisms. Macrophages and mast cells, part of the innate immune system, trigger immune responses and perform particular effector functions. The present study compared toxicological and functional effects of cadmium in two models of murine macrophages (RAW264.7 and NR8383 cell lines) and two models of murine mast cells (MC/9 and RBL-2H3 cell lines). Cadmium was selected as a model compound because its known potential to induce reactive oxygen species and its relevance as an environmental contaminant. Mechanisms of toxicity, such as redox imbalance and apoptosis induction were measured in stationary cells, while functional outcome effects were measured in activated cells. Cadmium-depleted glutathione antioxidant in all four cell lines tested although reactive oxygen species was not significantly increased. Mast cells had full dose-response depletion of glutathione below cytotoxic levels while in macrophages the depletion was not complete. Functional endpoints tumour necrosis factor-alpha and nitrite production in lipopolysaccharide-activated macrophages were increased by cadmium exposure. In contrast, mast cell lipopolysaccharide-induced tumour necrosis factor-alpha and IgE-mediated histamine release were reduced by cadmium. These data indicate potentially differential effects of cadmium among murine innate immune cell types, where mast cells would be more susceptible to oxidative stress and their function might be at a higher risk to be modulated compared to macrophages.
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http://dx.doi.org/10.1002/jat.3788DOI Listing
July 2019

Biomarker responses and biotransformation capacity in Arctic and temperate benthic species exposed to polycyclic aromatic hydrocarbons.

Sci Total Environ 2019 Apr 15;662:631-638. Epub 2019 Jan 15.

Sub-department of Toxicology, Department of Agrotechnology and Food Sciences, Wageningen University, P.O. Box 8000, 6700 EA Wageningen, the Netherlands.

Monitoring parameters for the assessment of oil and gas related contaminants and their biological effects need validation before application in the Arctic. For such monitoring purposes, we evaluated the potential use of three biomarkers (acetylcholinesterase, acyl-CoA oxidase and glutathione S-transferase) for application to an Arctic bivalve (Astarte borealis) and determined the body residue of pyrene and two pyrene metabolites (1-hydroxypyrene and pyrene-1-glucuronide) in Arctic benthic species (bivalve: Macoma calcarea; polychaete: Nephtys ciliata) and temperate benthic species (bivalve: Limecola balthica; polychaete: Alitta virens) in order to establish the potential of polycyclic aromatic hydrocarbons (PAHs) metabolite profiles as biomarkers of exposure in such species. Experimental PAH exposure levels were probably too low (0.2-1.7 mg/kg dry weight in sediment) to induce or inhibit biomarker responses in A. borealis. Concentrations of pyrene and pyrene metabolites varied between species, although no consistent patterns could be established among taxonomic groups and locations. Metabolites made up to 79% of the total pyrene concentrations, indicating that basal metabolic activity is affecting pyrene kinetics even at low concentrations in all species. This indicates that Arctic and temperate species could show similar metabolism patterns of PAHs, although more insight into the effects of confounding factors is needed.
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http://dx.doi.org/10.1016/j.scitotenv.2019.01.034DOI Listing
April 2019

Bioaccumulation of polycyclic aromatic hydrocarbons by arctic and temperate benthic species.

Environ Toxicol Chem 2019 04 27;38(4):883-895. Epub 2019 Feb 27.

Aquatic Ecology and Water Quality Management Group, Department of Environmental Sciences, Wageningen University, Wageningen, The Netherlands.

Increasing oil and gas activities may substantially increase chemical stress to benthic ecosystems in the Arctic, and it is necessary to evaluate such environmental risks in these systems. Risk assessment procedures for oil-related compounds (e.g., polycyclic aromatic hydrocarbons [PAHs]) should address differences in exposure between Arctic and temperate benthos. We compare for the first time the bioaccumulation of PAHs by Arctic benthic invertebrate species with that of temperate species, based on their biota-sediment accumulation factors (BSAFs). Measured PAH BSAFs were generally higher in temperate bivalves (Limecola balthica) than in Arctic bivalves (Macoma calcarea), whereas BSAFs in Arctic polychaetes (Nephtys ciliata) were higher than in temperate polychaetes (Alitta virens). Differences in measured BSAFs were explained by species-specific feeding modes and traits. However, modeled BSAFs revealed that steady state was not likely to be reached in the 28-d tests for all PAHs and organisms. Due to the low numbers of individuals, most species-specific parameters were too uncertain to reveal differences between Arctic and temperate species. The results of the present study suggest that data from temperate species could be used as a surrogate for Arctic species in risk assessment. Environ Toxicol Chem 2019;38:883-895. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
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http://dx.doi.org/10.1002/etc.4366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850439PMC
April 2019

Hatching failure and accumulation of organic pollutants through the terrestrial food web of a declining songbird in Western Europe.

Sci Total Environ 2019 Feb 12;650(Pt 1):1547-1553. Epub 2018 Sep 12.

Institute for Water and Wetland Research, Animal Ecology and Physiology & Experimental Plant Ecology, Radboud University, PO Box 9100, 6500 GL Nijmegen, the Netherlands.

Population growth in passerine birds is largely driven by fecundity. If fecundity is affected, for instance by hatching failure, populations may decline. We noted high hatching failure of up to 27% per year in relict populations of the Northern wheatear (Oenanthe oenanthe) in The Netherlands, a strongly declining, migratory passerine in Europe. This hatching failure itself can cause population decline, irrespective of other adverse factors. Additionally, we investigated the cause of hatching failure. Unhatched eggs showed egg yolk infections or embryonic malformations, part of which is associated with the actions of dioxin-like compounds (DLCs). Indeed, DLCs appear to bioaccumulate in the local foodweb, where the soil contained only background concentrations, similar to those found at many other locations. DLC concentrations in Dutch eggs were six-fold higher than those in a reference population in Sweden, where egg failure was only 6%. However, Northern wheatears appear to be only moderately sensitive to the actions of DLCs, because of their specific Ah-receptor type which may moderate the receptor mediated effects of DLCs. This indicates that the concentrations of DLCs, although elevated, may not have caused the embryo malformations or the low hatching rates. We discuss whether other toxins may be important or imbalances in the nutrition and if inbreeding may play a larger role than expected.
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http://dx.doi.org/10.1016/j.scitotenv.2018.09.138DOI Listing
February 2019

Use of proteomics to detect sex-related differences in effects of toxicants: implications for using proteomics in toxicology.

Crit Rev Toxicol 2018 09 26;48(8):666-681. Epub 2018 Sep 26.

Division of Toxicology, Wageningen University, Wageningen, The Netherlands.

This review provides an overview of results obtained when using proteome analysis for detecting sex-based differences in response to toxicants. It reveals implications to be taken into account when considering the use of proteomics in toxicological studies. It appears that results may differ when studying the same chemical in the same species in different target tissues. Another result of interest is the limited dose-response behavior of differential abundance patterns observed in studies where more than one dose level is tested. It is concluded that use of proteomics to study differences in modes of action of toxic compounds is an active area of research. The examples from use of proteomics to study sex-dependent differences also reveal that further studies are needed to provide reliable insight in modes of action, novel biomarkers or even novel therapies. To eventually reach this aim for this and other toxicological endpoints, it is essential to consider background variability, consequences of timing of toxicant administration, dose-response behavior, relevant species and target organ, species and organ variability and the presence of proteoforms.
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http://dx.doi.org/10.1080/10408444.2018.1509941DOI Listing
September 2018

Mercury associated neurochemical response in Arctic barnacle goslings (Branta leucopsis).

Sci Total Environ 2018 May 27;624:1052-1058. Epub 2017 Dec 27.

Arctic Centre, University Groningen, P.O. Box 716, 9700 AS Groningen, The Netherlands.

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http://dx.doi.org/10.1016/j.scitotenv.2017.12.191DOI Listing
May 2018

Avoidance tests as a tool to detect sublethal effects of oil-impacted sediments.

Environ Toxicol Chem 2018 06 30;37(6):1757-1766. Epub 2018 Apr 30.

Aquatic Ecology and Water Quality Management Group, Department of Environmental Sciences, Wageningen University, Wageningen, The Netherlands.

Currently, risk assessment for oil contamination does not consider behavioral responses of benthos to oil toxicity. Avoidance of oil-contaminated sediment by benthic amphipods, however, may be a highly sensitive endpoint for sublethal effects of commonly used distillate fuels. In the present study, the avoidance behavior of temperate freshwater (Gammarus pulex) and marine (Gammarus locusta) amphipods was tested by allowing them to choose between a reference sediment and a distillate marine grade A (DMA) oil-spiked sediment. Avoidance of DMA-spiked sediment at 1000 mg/kg dry weight was significant within the total exposure time (96 h) in G. pulex and within the first 72 h in G. locusta in 1 of 2 tests. Absence of DMA avoidance at lower concentrations (≤250 mg/kg dry wt) indicates that test species can only detect DMA above these concentrations. However, sensitivity to oil may vary according to the phenology and physiological conditions of the populations involved, such as the species temperature tolerance and reproductive stage. The results suggest that avoidance tests may be used as an alternative to traditional chronic toxicity tests provided that a causal link between avoidance and long-term effects can be established. Environ Toxicol Chem 2018;37:1757-1766. © 2018 SETAC.
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http://dx.doi.org/10.1002/etc.4129DOI Listing
June 2018

Effects of Systematic Variation in Size and Surface Coating of Silver Nanoparticles on Their In Vitro Toxicity to Macrophage RAW 264.7 Cells.

Toxicol Sci 2018 03;162(1):79-88

Division of Toxicology, Wageningen University, WE 6708 Wageningen, The Netherlands.

In literature, varying and sometimes conflicting effects of physicochemical properties of nanoparticles (NPs) are reported on their uptake and effects in organisms. To address this, small- and medium-sized (20 and 50 nm) silver nanoparticles (AgNPs) with specified different surface coating/charges were synthesized and used to systematically assess effects of NP-properties on their uptake and effects in vitro. Silver nanoparticles were fully characterized for charge and size distribution in both water and test media. Macrophage cells (RAW 264.7) were exposed to these AgNPs at different concentrations (0-200 µg/ml). Uptake dynamics, cell viability, induction of tumor necrosis factor (TNF)-α, ATP production, and reactive oxygen species (ROS) generation were assessed. Microscopic imaging of living exposed cells showed rapid uptake and subcellular cytoplasmic accumulation of AgNPs. Exposure to the tested AgNPs resulted in reduced overall viability. Influence of both size and surface coating (charge) was demonstrated, with the 20-nm-sized AgNPs and bovine serum albumin (BSA)-coated (negatively charged) AgNPs being slightly more toxic. On specific mechanisms of toxicity (TNF-α and ROS production) however, the AgNPs differed to a larger extent. The highest induction of TNF-α was found in cells exposed to the negatively charged AgNP_BSA, both sizes (80× higher than control). Reactive oxygen species induction was only significant with the 20 nm positively charged AgNP_Chit.
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http://dx.doi.org/10.1093/toxsci/kfx228DOI Listing
March 2018

Indices of stress and immune function in Arctic barnacle goslings (Branta leucopsis) were impacted by social isolation but not a contaminated grazing environment.

Sci Total Environ 2017 Dec 25;601-602:132-141. Epub 2017 May 25.

Arctic Centre, University of Groningen, Aweg 30, 9718 CW Groningen, The Netherlands. Electronic address:

In many areas around the Arctic remains and spoil heaps of old mines can be found, which have been abandoned after their heydays. Runoff from tailings of these abandoned mines can directly contaminate the local environment with elevated concentrations of trace metals. Few studies have investigated the possible negative effects of contaminants on Arctic terrestrial animals that use these areas. Trace metals can accumulate in animals and this accumulation has been linked to negative effects on fitness. Both, the hypothalamus-pituitary-adrenal (HPA) axis and/or the immune system have been named as possible underlying causes for these observations. Free-living animals are often exposed to multiple stressors simultaneously, however, and this is often not considered in studies on the effects of contaminants on animal physiology. Here, we performed a study on Spitsbergen (Svalbard) taking both potential effects of trace metal contamination and social stress into account. We investigated experimentally effects of exposure to contaminants from a historic coal mine area on plasma corticosterone levels and on four innate immune parameters (haemolysis, haemagglutination, haptoglobin-like activity and nitric oxide) before and after social isolation in human-raised barnacle goslings (Branta leucopsis). Baseline corticosterone and immune parameters were not affected by mine-exposure. After social isolation, mine goslings tended to show decreased haemagglutination in comparison with control goslings, but we detected no difference in the other measures. Social isolation increased corticosterone and decreased haptoglobin-like activity in all goslings. Immunology and corticosterone levels of barnacle goslings thus seem unaffected, at least on the short term, by Arctic coal mining contamination.
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http://dx.doi.org/10.1016/j.scitotenv.2017.05.183DOI Listing
December 2017

Analysis of fullerenes in soils samples collected in The Netherlands.

Environ Pollut 2016 Dec 20;219:47-55. Epub 2016 Sep 20.

University of Amsterdam - IBED, Science Park 904, 1098 XH Amsterdam, The Netherlands; KWR, Watercycle Research Institute, P.O. Box 1072, 3433 PE Nieuwegein, The Netherlands.

Fullerenes are carbon based nanoparticles that may enter the environment as a consequence of both natural processes and human activities. Although little is known about the presence of these chemicals in the environment, recent studies suggested that soil may act as a sink. The aim of the present work was to investigate the presence of fullerenes in soils collected in The Netherlands. Samples (n = 91) were taken from 6 locations and analyzed using a new developed LC-QTOF-MS method. The locations included highly trafficked and industrialized as well as urban and natural areas. In general, C was the most abundant fullerene found in the environment, detected in almost a half of the samples and at concentrations in the range of ng/kg. Other fullerenes such as C and an unknown structure containing a C cage were detected to a lower extent. The highest concentrations were found in the proximity of combustion sites such as a coal power plant and an incinerator, suggesting that the nanoparticles were unintentionally produced during combustions processes and reached the soil through atmospheric deposition. Consistent with other recent studies, these results show that fullerenes are widely present in the environment and that the main route for their entrance may be due to human activities. These data will be helpful in the understanding of the distribution of fullerenes in the environment and for the study of their behavior and fate in soil.
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http://dx.doi.org/10.1016/j.envpol.2016.09.034DOI Listing
December 2016

Bioaccumulation of polycyclic aromatic hydrocarbons, polychlorinated biphenyls and hexachlorobenzene by three Arctic benthic species from Kongsfjorden (Svalbard, Norway).

Mar Pollut Bull 2016 Nov 27;112(1-2):65-74. Epub 2016 Aug 27.

Aquatic Ecology and Water Quality Management Group, Department of Environmental Sciences, Wageningen University, P.O. Box 47, 6700 AA Wageningen, The Netherlands; IMARES, Institute for Marine Resources & Ecosystem Studies, Wageningen UR, P.O. Box 77, 4400 AB Yerseke, The Netherlands.

The predicted expansion of oil and gas (O&G) activities in the Arctic urges for a better understanding of impacts of these activities in this region. Here we investigated the influence of location, feeding strategy and animal size on the bioaccumulation of Polycyclic Aromatic Hydrocarbons (PAHs), Polychlorinated Biphenyls (PCBs) and Hexachlorobenzene (HCB) by three Arctic benthic species in Kongsfjorden (Svalbard, Norway). No toxicity was expected based on biota PAH critical body residues. Biota PCB levels were mainly below limit of detection, whereas samples were moderately polluted by HCB. PAH concentrations in biota and Biota Sediment Accumulation Factors (BSAFs) were generally higher in Blomstrandhalvøya than in Ny-Ålesund, which was explained by a higher abundance of black carbon in Ny-Ålesund harbour. BSAFs differed significantly among species and stations. We conclude that contaminant body residues are a less variable and more straightforward monitoring parameter than sediment concentrations or BSAFs in Arctic benthos.
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http://dx.doi.org/10.1016/j.marpolbul.2016.08.041DOI Listing
November 2016

Properties of silver nanoparticles influencing their uptake in and toxicity to the earthworm Lumbricus rubellus following exposure in soil.

Environ Pollut 2016 Nov 11;218:870-878. Epub 2016 Aug 11.

Division of Toxicology, Wageningen University and Research Centre, Tuinlaan 5, 6703 HE, Wageningen, The Netherlands. Electronic address:

Physicochemical properties of nanoparticles influence their environmental fate and toxicity, and studies investigating this are vital for a holistic approach towards a comprehensive and adequate environmental risk assessment. In this study, we investigated the effects of size, surface coating (charge) of silver nanoparticles (AgNPs) - a most commonly-used nanoparticle-type, on the bioaccumulation in, and toxicity (survival, growth, cocoon production) to the earthworm Lumbricus rubellus. AgNPs were synthesized in three sizes: 20, 35 and 50 nm. Surface-coating with bovine serum albumin (AgNP_BSA), chitosan (AgNP_Chit), or polyvinylpyrrolidone (AgNP_PVP) produced negative, positive and neutral particles respectively. In a 28-day sub-chronic reproduction toxicity test, earthworms were exposed to these AgNPs in soil (0-250 mg Ag/kg soil DW). Earthworms were also exposed to AgNO at concentrations below known EC. Total Ag tissue concentration indicated uptake by earthworms was generally highest for the AgNP_BSA especially at the lower exposure concentration ranges, and seems to reach a plateau level between 50 and 100 mg Ag/kg soil DW. Reproduction was impaired at high concentrations of all AgNPs tested, with AgNP_BSA particles being the most toxic. The EC for the 20 nm AgNP_BSA was 66.8 mg Ag/kg soil, with exposure to <60 mg Ag/kg soil already showing a decrease in the cocoon production. Thus, based on reproductive toxicity, the particles ranked: AgNP_BSA (negative) > AgNP_PVP (neutral) > Chitosan (positive). Size had an influence on uptake and toxicity of the AgNP_PVP, but not for AgNP_BSA nor AgNP_Chit. This study provides essential information on the role of physicochemical properties of AgNPs in influencing uptake by a terrestrial organism L. rubellus under environmentally relevant conditions. It also provides evidence of the influence of surface coating (charge) and the limited effect of size in the range of 20-50 nm, in driving uptake and toxicity of the AgNPs tested.
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http://dx.doi.org/10.1016/j.envpol.2016.08.016DOI Listing
November 2016

Use of terrestrial field studies in the derivation of bioaccumulation potential of chemicals.

Integr Environ Assess Manag 2016 Jan 8;12(1):135-45. Epub 2015 Dec 8.

NERC Centre for Ecology and Hydrology, Lancaster, United Kingdom.

Field-based studies are an essential component of research addressing the behavior of organic chemicals, and a unique line of evidence that can be used to assess bioaccumulation potential in chemical registration programs and aid in development of associated laboratory and modeling efforts. To aid scientific and regulatory discourse on the application of terrestrial field data in this manner, this article provides practical recommendations regarding the generation and interpretation of terrestrial field data. Currently, biota-to-soil-accumulation factors (BSAFs), biomagnification factors (BMFs), and bioaccumulation factors (BAFs) are the most suitable bioaccumulation metrics that are applicable to bioaccumulation assessment evaluations and able to be generated from terrestrial field studies with relatively low uncertainty. Biomagnification factors calculated from field-collected samples of terrestrial carnivores and their prey appear to be particularly robust indicators of bioaccumulation potential. The use of stable isotope ratios for quantification of trophic relationships in terrestrial ecosystems needs to be further developed to resolve uncertainties associated with the calculation of terrestrial trophic magnification factors (TMFs). Sampling efforts for terrestrial field studies should strive for efficiency, and advice on optimization of study sample sizes, practical considerations for obtaining samples, selection of tissues for analysis, and data interpretation is provided. Although there is still much to be learned regarding terrestrial bioaccumulation, these recommendations provide some initial guidance to the present application of terrestrial field data as a line of evidence in the assessment of chemical bioaccumulation potential and a resource to inform laboratory and modeling efforts.
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http://dx.doi.org/10.1002/ieam.1717DOI Listing
January 2016

Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife.

Environ Sci Technol 2014 9;48(15):8433-45. Epub 2014 Jul 9.

Patuxent Wildlife Research Center, U.S. Geological Survey, Beltsville, Maryland 20705, United States.

Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.
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http://dx.doi.org/10.1021/es501740nDOI Listing
October 2015

Effects of silver nanoparticles (NM-300K) on Lumbricus rubellus earthworms and particle characterization in relevant test matrices including soil.

Environ Toxicol Chem 2014 Apr;33(4):743-52

Alterra, Wageningen UR, Wageningen, The Netherlands; Division of Toxicology, Wageningen University, Wageningen, The Netherlands.

The impact of silver nanoparticles (AgNP; at 0 mg Ag/kg, 1.5 mg Ag/kg, 15.4 mg Ag/kg, and 154 mg Ag/kg soil) and silver nitrate (AgNO3 ; 15.4 mg Ag/kg soil) on earthworms, Lumbricus rubellus, was assessed. A 4-wk exposure to the highest AgNP treatment reduced growth and reproduction compared with the control. Silver nitrate (AgNO3 ) exposure also impaired reproduction, but not as much as the highest AgNP treatment. Long-term exposure to the highest AgNP treatment caused complete juvenile mortality. All AgNP treatments induced tissue pathology. Population modeling demonstrated reduced population growth rates for the AgNP and AgNO3 treatments, and no population growth at the highest AgNP treatment because of juvenile mortality. Analysis of AgNP treated soil samples revealed that single AgNP and AgNP clusters were present in the soil, and that the total Ag in soil porewater remained high throughout the long-term experiment. In addition, immune cells (coelomocytes) of earthworms showed sensitivity to both AgNP and AgNO3 in vitro. Overall, the present study indicates that AgNP exposure may affect earthworm populations and that the exposure may be prolonged because of the release of a dissolved Ag fraction to soil porewater.
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http://dx.doi.org/10.1002/etc.2487DOI Listing
April 2014

In vitro nanoparticle toxicity to rat alveolar cells and coelomocytes from the earthworm Lumbricus rubellus.

Nanotoxicology 2014 Feb 27;8(1):28-37. Epub 2012 Nov 27.

Alterra, Wageningen University and Research Centre , Wageningen , The Netherlands.

Sensitivity of immune cells (coelomocytes) of Lumbricus rubellus earthworms was investigated for exposure to selected nanoparticles, in order to obtain further insight in mechanisms of effects observed after in vivo C60 exposure. In the in vivo study, tissue damage appeared to occur without accompanying increased immune responses. Coelomocytes exposed in vitro to C60 showed no decrease of their cellular viability, but demonstrated a decrease in gene expression of the cytokine-like protein CCF-1, indicating immunosuppression. Experiments with NR8383 rat macrophage cells and tri-block copolymer nanoparticles were used to compare sensitivity and to demonstrate the usefulness of coelomocytes as a test system for nano-immunotoxicity, respectively. Overall, the results imply that sensitivity towards nanoparticles differs between cell types and nanoparticles. Moreover, this study indicates that injuries in absence of an immune response, observed after in vivo C60 exposure in our earlier work, are caused by immunosuppression rather than coelomocyte mortality.
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http://dx.doi.org/10.3109/17435390.2012.744857DOI Listing
February 2014
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