Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Genomics of sex allocation in the parasitoid wasp Nasonia vitripennis
    Pannebakker, Bart A. ; Cook, Nicola ; Heuvel, Joost van den; Zande, Louis van de; Shuker, David M. - \ 2020
    BMC Genomics 21 (2020). - ISSN 1471-2164
    Genetic reference panel - Genome-wide association study (GWAS) - Local mate competition - Nasonia - Oviposition - Parasitoid wasp - Sex allocation - Single nucleotide polymorphism (SNP)

    Background: Whilst adaptive facultative sex allocation has been widely studied at the phenotypic level across a broad range of organisms, we still know remarkably little about its genetic architecture. Here, we explore the genome-wide basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, perhaps the best studied organism in terms of sex allocation, and well known for its response to local mate competition. Results: We performed a genome-wide association study (GWAS) for single foundress sex ratios using iso-female lines derived from the recently developed outbred N. vitripennis laboratory strain HVRx. The iso-female lines capture a sample of the genetic variation in HVRx and we present them as the first iteration of the Nasonia vitripennis Genome Reference Panel (NVGRP 1.0). This panel provides an assessment of the standing genetic variation for sex ratio in the study population. Using the NVGRP, we discovered a cluster of 18 linked SNPs, encompassing 9 annotated loci associated with sex ratio variation. Furthermore, we found evidence that sex ratio has a shared genetic basis with clutch size on three different chromosomes. Conclusions: Our approach provides a thorough description of the quantitative genetic basis of sex ratio variation in Nasonia at the genome level and reveals a number of inter-related candidate loci underlying sex allocation regulation.

    Spray drift simulations to estimate the exposure of residents to pesticides close to a sprayed fiel
    Holterman, H.J. ; Zande, J.C. van de - \ 2020
    Wageningen : Stichting Wageningen Research, Wageningen Plant Research (Report / Stichting Wageningen Research, Wageningen Plant Research WPR-878) - 69
    Downwind deposits and airborne emissions of spray drift after a pesticide application on flower bulb fields were computed using the IDEFICS spray drift model. The simulations closely followed real spray applications that took place on selected flower bulb fields. Spray deposits on the ground down to 5 m off the downwind field edge were determined. Vertical airborne emission profiles were determined at the same distance. 14 cases were studied; the airborne emission results of these are to be used as input for a spray and vapour dispersion model.
    Probabilistic risk assessment for watercourses exposed to spray drift in fruit growing in the Netherlands
    Holterman, H.J. ; Zande, J.C. van de; Wipfler, E.L. ; Boesten, J.J.T.I. ; Huijsmans, J.F.M. - \ 2020
    In: Aspects of Applied Biology. - Brighton : Association of Applied Biologists, 2020 (Aspects of Applied Biology ) - p. 255 - 262.
    This is the pre-edited version of the following article: Holterman, H. J., van de Zande, J. C., Wipfler, E. L., Boesten, J. J. T. I., & Huijsmans, J. F. M. (2019). Probabilistic risk assessment for watercourses exposed to spray drift in fruit growing in the Netherlands. In Aspects of Applied Biology: International Advances in Pesticide Application (144 ed., pp. 255-262). (Aspects of Applied Biology; Vol. 144). Brighton: Association of Applied Biologists, 2020., which has been published in final form at https://www.aab.org.uk/aspects-of-applied-biology Deposition of spray drift onto surface waters is a major cause for the risk of exposure to pesticides for aquatic organisms. This risk is particularly high for surface waters alongside pome fruit orchards, where pesticide sprays are applied in a sideways or an upward direction. Recently a spray drift model has been developed to estimate pesticide deposits onto downwind off-target areas next to fruit orchards. Using this spray drift model, an exposure assessment model has been developed to estimate risk of exposure to pesticides for aquatic organisms in edge-of-field watercourses next to pome fruit orchards in the Netherlands. For arable crops, typically, the risk of exposure is much less, considering pesticide concentrations in the edge-of-field watercourse. However, the total area for arable crops is much higher than that for fruit orchards. This paper describes the probabilistic processes concerning the countrywide risk assessment using a exposure model for one field and one ditch. Spatial and temporal variables are distinguished. Spatial variables include regional distributions of orchards and different types of watercourses, various water levels and continuously varying growth stages during the year. Temporal variables include frequency distributions of wind speed and direction and ambient temperature. 90% risk levels of predicted environmental concentrations (PEC) in surface water can be determined for various spray application schemes including multiple spray applications during a year. In an extensive simulation study the PECs in the watercourses were computed for all possible spatial configurations. A spatio-temporal statistical analysis on these simulations resulted in a quantitative risk assessment for a representative set of spray application schemes. Various model features (including drift mitigation, crop-free zones) result in a versatile exposure assessment model with a high level of realism. The spray drift deposits onto the water surface can be used as input for models describing the fate of pesticides in the watercourses. In this way, a realistic simulation study on the exposure to and fate of pesticides in surface waters can be performed to quantify exposure risk levels for aquatic organisms. The countrywide exposure risk model supports higher-tier assessment studies for the authorization of plant protection products.
    The gut barrier and the fate of engineered nanomaterials : a view from comparative physiology
    Zande, Meike Van Der; Jemec Kokalj, Anita ; Spurgeon, David J. ; Loureiro, Susana ; Silva, Patrícia V. ; Khodaparast, Zahra ; Drobne, Damjana ; Clark, Nathaniel J. ; Brink, Nico W. Van Den; Baccaro, Marta ; Gestel, Cornelis A.M. Van; Bouwmeester, Hans ; Handy, Richard D. - \ 2020
    Environmental Science: Nano covers the benefits... (2020)7. - ISSN 2051-8153 - p. 1874 - 1898.
    The structure of the gut barrier and luminal chemistry in non-mammalian vertebrates and invertebrates has been given little attention with respect to the dietary uptake of engineered nanomaterials (ENMs). This review compares the diversity of gut anatomy in selected species used for regulatory toxicity testing, especially in relation to gut lumen chemistry and the behaviour of ENMs, and the gut as a barrier to ENMs. High ionic strength, the presence of divalent ions and organic matter promote particle aggregation in the lumen. The redox chemistry of the gut offers reducing conditions for ENM transformation, and corona formation will depend on the gut contents. Areas of low pH in the gut lumen in several species will promote the dissolution of metallic ENMs. There is a protective unstirred layer over the surface of the epithelium that may concentrate ENMs. Some organisms, especially vertebrates, can slough mucus to remove this adsorbed nanomaterial and lower bioavailability. Invertebrates also have protective layers of cuticle or peritrophic membranes that will modulate ENM uptake. Paracellular uptake of ENMs is unlikely. Transcellular uptake via vesicular-dependent pathways remains the most likely route across the gut epithelium. Most species have receptor-mediated endocytosis pathways and/or macropinocytosis in the gut epithelium. Crucially, many invertebrates have another potential pathway via ‘intracellular digestion’ uptake routes leading into the gut epithelium, and with gut associated immune cells being a potential route for ENM translocation across the epithelium. The basal lamina provides another barrier prior to the internal compartments of many animals. The features of the gut lumen and epithelium can limit the uptake of ENMs across the gut barrier in vivo, although some ENMs are detected in the tissues. Invertebrates also have the ability for biogenic mineral formation at the nano scale inside tissues. In conclusion, despite the diverse structural anatomies of the gut barrier of animals, some common features in the gut lumen chemistry tend to promote particle aggregation and settling onto the gut surface. The functional anatomy ensures the gut remains a formidable barrier to ENMs, and with some potential novel uptake processes in invertebrates that are not present in vertebrate animals
    International advances in pesticide application at Mercure Brighton Seafront Hotel, Brighton, Sussex, UK on 28-30 January 2020
    Balsari, Paolo ; Butler Ellis, Claire ; Cooper, Simon ; Gil, Emilio ; Glaas, Richard ; Magri, Ben ; Mountford Smith, Colin ; Nuyttens, David ; Robinson, Tom ; Thomas, James ; Zande, Jan van de - \ 2020
    Wellesbourne : Association of Applied Biologists, 2020 (Aspects of applied biology 144) - 324
    In vitro testing strategies for hazard assessment of nanoparticles
    Abdelkhaliq, Ashraf - \ 2020
    Wageningen University. Promotor(en): I.M.C.M. Rietjens, co-promotor(en): H. Bouwmeester; M. van der Zande. - Wageningen : Wageningen University - ISBN 9789463953900 - 218

    In chapter 1 of this thesis, an overview of the main applications of NPs was provided and the main properties of NPs were briefly introduced. In addition, some of the key methods that are currently used in the toxicological safety assessment of NPs were presented. The aim of the thesis was introduced which was to investigate the potential of different in vitro methods combined with high-end analytical techniques as a testing strategy to study the toxicokinetic and toxicodynamic properties of silver (Ag) and polystyrene (PS) NPs and set priorities in their further safety testing. The current state of the art of the in vitro methods used in the studies in this thesis and the outline of the thesis were also presented.

    In chapter 2, the influences of the size and surface chemistry of pristine PSNPs on the protein corona formation and subsequent uptake/association and transport of these NPs through a Caco-2 intestinal cell model were studied. Four negatively charged PSNPs of different sizes (50 and 200 nm) and with different surface chemistries (sulfone or carboxyl groups) were studied. The protein coronas of these PSNPs were analysed by LC-MS/MS which showed subtle differences in the protein composition of especially the two PSNPs with different surface chemistries. In further experiments, the impact of surface chemistry on the cellular uptake/association and transport was characterised using high-content imaging analysis. These experiments demonstrated that the PSNPs with sulfone surface groups were associated with the cells to a significantly higher extent than the PSNPs with carboxyl surface groups. No clear effect of the size of the PSNPs on the cellular uptake/association was noted. Also, the transport of the PSNPs with sulfone surface groups through the monolayer of cells was significantly higher than that of PSNPs with carboxyl surface groups.

    The general conclusion was that the composition of the protein corona and the PSNPs surface chemistry influence the cellular NPs uptake/association and transport, with the effect of the NP surface chemistry outweighing the impact of NPs size on the cellular uptake/associations and transport. These results might be predictive of the intestinal transport of NPs. Still, further studies are required to identify which corona proteins affect the uptake and transport of NPs.

    Chapter 3 described an investigation on the impact of the biochemical conditions within the human digestive tract on the intestinal fate of AgNPs with different surface chemistries. On top of that, the transport of these AgNPs across an intestinal in vitro model of Caco-2/HT29-MTX cells was evaluated. An in vitro digestion model was used to simulate the human digestion processes. Two 50 nm negatively charged AgNPs with different surface chemistries were used, lipoic acid (LA) AgNPs and citrate (Cit) AgNPs next to silver nitrate (AgNO3) as a source of ionic silver (Ag+). The co-culture model was exposed to different concentrations of pristine and in vitro digested (IVD) AgNPs or AgNO3 for 24 hr. Using ICP-MS and spICP-MS, the size distribution, dissolution, particle concentration (mass- and number-based) and total silver content of the AgNPs were characterized before and after digestion and in the apical, basolateral and cellular compartments of the Caco-2/HT29-MTX intestinal epithelial model. The surface chemistry of AgNPs had a significant influence on their dissolution and on their biological interactions with the Caco-2/HT29-MTX intestinal model. In general, a significant fraction of the AgNPs dissolved during the digestion up to 86 - 92% and 48 – 70% of the original amount of NPs for the (LA) and (Cit) AgNPs, respectively. Exposure of the monolayer of intestinal cells to increasing concentrations of pristine or IVD AgNPs resulted in a concentration dependent increase of total Ag and AgNPs content in the cellular fractions. The cellular concentrations were significantly lower following exposure to IVD AgNPs compared to the pristine AgNPs. The effect of the surface chemistry on the cellular concentration of Ag was only detected upon exposure to pristine AgNPs, while this difference disappeared upon exposure to IVD AgNPs.

    Transport of Ag across the intestinal model layer, as either total Ag or AgNPs, was limited (< 0.1%) following exposure to pristine and IVD AgNPs. De novo formation of AgNPs was shown in the exposure suspensions of IVD AgNPs and AgNO3 and in the cellular fractions, upon cellular exposure to pristine and IVD AgNO3. In conclusion, the surface chemistry of AgNPs and the biochemical conditions during in vitro digestion influences the dissolution and also influences the uptake/association within the Caco-2/HT29-MTX monolayer. This highlights the need to take in vitro digestion into account when studying nanoparticle toxicokinetics in an intestinal cellular in vitro model system. The observation that dissolution characteristics of NPs may change upon digestion could be of added value in the safe(r)-by-design NPs development.

    Chapter 4 presented the outcomes from combining the BeWo b30 placental transport model and the embryonic stem cell test (EST) to investigate the capability of pristine AgNPs of different surface chemistries and aged AgNPs (Ag2S NPs) to cross the placental barrier and induce in vitro developmental toxicity. AgNO3 was used as a source of Ag+. The pristine negatively charged AgNPs used in this study were similar to the ones used in chapter 3 while in addition also positively charged 50 nm branched polyethylenimine (BPEI) AgNPs were included in the study. The size distribution, dissolution, particle concentration (mass- and number-based) and total Ag content of the AgNPs in the apical, basolateral and cellular compartments of the BeWo b30 placental transport model at different time points was characterized using ICP-MS and spICP-MS. The ability of the AgNPs to cross the BeWo b30 cell layer was limited and dependent on the surface chemistry of these AgNPs. The particles detected in the basolateral compartment could result from transport of the original AgNPs and/or from the de novo formed AgNPs in the basolateral compartment from Ag+ that was transported.

    The in vitro developmental toxicity of the AgNPs was investigated by characterizing their potential to inhibit the differentiation of mouse embryonic stem cells (mESCs) into beating cardiomyocytes using the EST. The observed inhibitory effects of the AgNPs on differentiation of mESCs were most likely the result of cytotoxicity rather than specific effects related to developmental toxicity as the effects on differentiation of the mESCs were only detected at cytotoxic concentrations. Compared to the pristine AgNPs, the aged Ag2S NPs were significantly less cytotoxic, transported less across the BeWo cell layer and did not induce in vitro developmental toxicity. In conclusion, the combination of the BeWo placental transport model with the mESCs differentiation assay appeared to provide a valuable alternative in vitro methodology for prenatal developmental toxicity testing and prioritization for further safety testing of AgNPs, with aged Ag2S NPs appearing to present less of a hazard than pristine AgNPs.

    In chapter 5, the In-Cell Western (ICW)-γ-H2AX assay was evaluated as an alternative in vitro assay to detect the potential of aged AgNPs and pristine AgNPs to induce phosphorylation of H2AX in HepG2 liver cells. AgNO3 was used as source of Ag+ to test the effects of Ag+ themselves. The γ-H2AX induction detected was higher after 24 hr exposure compared to 4 hr and was accompanied by a significant cytotoxicity in the HepG2 cells. The increased induction of γ-H2AX measured could be due to the cytotoxicity that occurred at the same concentrations which can result in DNA damage resulting in an increased induction of γ-H2AX. This suggests potential false-positive confounders limiting the use of the ICW-γ-H2AX assay, in the form as applied in chapter 5, for evaluation of the genotoxicity of NPs. Additionally, the potential of the AgNPs to induce ROS production, as a potential underlying mechanism of induction of the cytotoxicity and/or DNA-DSBs, was assessed in HepG2 cells. No increase in ROS levels was measured upon exposure of the cells to the AgNPs for 4 or 24 hr and in the absence of cells, while an increase in ROS levels was detected upon AgNO3 exposure of the cells and in the absence of cells.

    In conclusion, the surface chemistry of AgNPs has a significant influence on their cytotoxic effects and the accompanying induction of γ-H2AX levels in HepG2 cells. The aged Ag2S NPs were biologically less active in inducing both cytotoxicity and γ-H2AX levels, as these effects were absent in the dose range tested. The absence of cellular ROS generation upon exposure to all AgNPs indicates that the observed effects were not ROS-mediated. Additional tests, to rule out apoptotic mediated false-positive signals, need to be combined with the ICW-γ-H2AX assay, to render this interesting assay into a robust screening method for the potential genotoxicity of NPs.

    Chapter 6 of the present thesis included a general discussion of the results of the previous chapters and highlights on future perspectives for research in the field of in vitro nanotoxicology.

    Overall, the work presented in this thesis illustrated the role of surface chemistry and the status of the NPs (pristine or aged and/or digested) on the toxicological behaviour of NPs. Besides, the combination of different in vitro models with high-end analytical techniques was shown to;  1) provide in-depth understanding of the biological behaviour of NPs, 2) assure the value of the alternative in vitro models as a testing strategy for potential hazards that could be induced by NPs and 3) assist in setting priorities for in vivo testing and contributing to reduction, refinement and replacement (3Rs) of animal testing required for the safety evaluation of NPs.

    Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models
    Kulthong, Kornphimol ; Duivenvoorde, Loes ; Sun, Huiyi ; Confederat, Samuel ; Wu, Jiaqing ; Spenkelink, Bert ; Haan, Laura de; Marin, Victor ; Zande, Meike van der; Bouwmeester, Hans - \ 2020
    Toxicology in Vitro 65 (2020). - ISSN 0887-2333
    Bioavailability - Dynamic flow - Gut-on-chip - Microfluidics - Transport

    Dynamic flow in vitro models are currently widely explored for their applicability in drug development research. The application of gut-on-chip models in toxicology is lagging behind. Here we report the application of a gut-on-chip model for biokinetic studies and compare the observed biokinetics of reference compounds with those obtained using a conventional static in vitro model. Intestinal epithelial Caco-2 cells were cultured on a porous membrane assembled between two glass flow chambers for the dynamic model, or on a porous membrane in a Transwell model. Confocal microscopy, lucifer yellow translocation, and alkaline phosphatase activity evaluation revealed that cells cultured in the gut-on-chip model formed tight, differentiated, polarized monolayers like in the static cultures. In the dynamic gut-on-chip model the transport of the high permeability compounds antipyrine, ketoprofen and digoxin was lower (i.e. 4.2-, 2.7- and 1.9-fold respectively) compared to the transport in the static Transwell model. The transport of the low permeability compound, amoxicillin, was similar in both the dynamic and static in vitro model. The obtained transport values of the compounds are in line with the compound Biopharmaceuticals Classification System. It is concluded that the gut-on-chip provides an adequate model for transport studies of chemicals.

    Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles
    Abdelkhaliq, Ashraf ; Zande, Meike van der; Peters, Ruud J.B. ; Bouwmeester, Hans - \ 2020
    Particle and Fibre Toxicology 17 (2020)1. - ISSN 1743-8977 - 1 p.
    Embryotoxicity - Placental transport - Silver nanoparticles - Single particle-ICP-MS - Surface chemistry

    BACKGROUND: Silver nanoparticles (AgNPs) are used extensively in various consumer products because of their antimicrobial potential. This requires insight in their potential hazards and risks including adverse effects during pregnancy on the developing fetus. Using a combination of the BeWo b30 placental transport model and the mouse embryonic stem cell test (EST), we investigated the capability of pristine AgNPs with different surface chemistries and aged AgNPs (silver sulfide (Ag2S) NPs) to cross the placental barrier and induce developmental toxicity. The uptake/association and transport of AgNPs through the BeWo b30 was characterized using ICP-MS and single particle (sp)ICP-MS at different time points. The developmental toxicity of the AgNPs was investigated by characterizing their potential to inhibit the differentiation of mouse embryonic stem cells (mESCs) into beating cardiomyocytes. RESULTS: The AgNPs are able to cross the BeWo b30 cell layer to a level that was limited and dependent on their surface chemistry. In the EST, no in vitro developmental toxicity was observed as the effects on differentiation of the mESCs were only detected at cytotoxic concentrations. The aged AgNPs were significantly less cytotoxic, less bioavailable and did not induce developmental toxicity. CONCLUSIONS: Pristine AgNPs are capable to cross the placental barrier to an extent that is influenced by their surface chemistry and that this transport is likely low but not negligible. Next to that, the tested AgNPs have low intrinsic potencies for developmental toxicity. The combination of the BeWo b30 model with the EST is of added value in developmental toxicity screening and prioritization of AgNPs.

    Impact of in vitro digestion on gastrointestinal fate and uptake of silver nanoparticles with different surface modifications
    Abdelkhaliq, Ashraf ; Zande, Meike van der; Undas, Anna K. ; Peters, Ruud J.B. ; Bouwmeester, Hans - \ 2020
    Nanotoxicology 14 (2020)1. - ISSN 1743-5390 - p. 111 - 126.
    bioavailability - in vitro digestion - Silver nanoparticles - single particle-ICP-MS - surface chemistry

    Nanomaterials, especially silver nanoparticles (AgNPs), are used in a broad range of products owing to their antimicrobial potential. Oral ingestion is considered as a main exposure route to AgNPs. This study aimed to investigate the impact of the biochemical conditions within the human digestive tract on the intestinal fate of AgNPs across an intestinal in vitro model of differentiated Caco-2/HT29-MTX cells. The co-culture model was exposed to different concentrations (250–2500 µg/L) of pristine and in vitro digested (IVD) AgNPs and silver nitrate for 24 h. ICP-MS and spICP-MS measurements were performed for quantification of total Ag and AgNPs. The AgNPs size distribution, dissolution, and particle concentration (mass- and number-based) were characterized in the cell fraction and in the apical and basolateral compartments of the monolayer cultures. A significant fraction of the AgNPs dissolved (86–92% and 48–70%) during the digestion. Cellular exposure to increasing concentrations of pristine or IVD AgNPs resulted in a concentration dependent increase of total Ag and AgNPs content in the cellular fractions. The cellular concentrations were significantly lower following exposure to IVD AgNPs compared to the pristine AgNPs. Transport of silver as either total Ag or AgNPs was limited (<0.1%) following exposure to pristine and IVD AgNPs. We conclude that the surface chemistry of AgNPs and their digestion influence their dissolution properties, uptake/association with the Caco-2/HT29-MTX monolayer. This highlights the need to take in vitro digestion into account when studying nanoparticle toxicokinetics and toxicodynamics in cellular in vitro model systems.

    Determination of spray drift and buffer zones in 3D crops using the ISO standard and new LiDAR methodologies
    Torrent, Xavier ; Gregorio, Eduard ; Rosell-Polo, Joan R. ; Arnó, Jaume ; Peris, Miquel ; Zande, Jan C. van de; Planas, Santiago - \ 2020
    Science of the Total Environment 714 (2020). - ISSN 0048-9697
    Hollow-cone nozzles - Light detection and ranging - Pesticide spraying - Remote sensing - Spray drift - Spray drift potential reduction

    Spray drift generated in the application of plant protection products in tree crops (3D crops) is a major source of environmental contamination, with repercussions for human health and the environment. Spray drift contamination acquires greater relevance in the EU Southern Zone due to the crops structure and the weather conditions. Hence, there is a need to evaluate spray drift when treating the most representative 3D crops in this area. For this purpose, 4 spray drift tests, measuring airborne and sedimenting spray drift in accordance with ISO 22866:2005, were carried out for 4 different crops (peach, citrus, apple and grape) in orchards of the EU Southern Zone, using an air-blast sprayer equipped with standard (STN) and spray drift reduction (DRN) nozzle types. A further 3 tests were carried out to test a new methodology for the evaluation of spray drift in real field conditions using a LiDAR system, in which the spray drift generated by different sprayer and nozzle types was contrasted. The airborne spray drift potential reduction (DPRV) values, obtained following the ISO 22866:2005, were higher than those for sedimenting spray drift potential reduction (DPRH) (63.82%–94.42% vs. 39.75%–69.28%, respectively). For each crop and nozzle type combination, a sedimenting spray drift model was also developed and used to determine buffer zone width. The highest buffer width reduction (STN vs DRN) was obtained in peach (˃75%), while in grape, citrus and apple only 50% was reached. These results can be used as the starting point to determine buffer zone width in the countries of the EU Southern Zone depending on different environmental threshold values. Tests carried out using LiDAR system demonstrated high capacity and efficiency of this system and this newly defined methodology, allowing sprayer and nozzle types in real field conditions to be differentiated and classified.

    Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies
    Santbergen, J.C. ; Zande, M. van der; Gerssen, A. ; Bouwmeester, H. ; Nielen, M.W.F. - \ 2020
    Analytical and Bioanalytical Chemistry 412 (2020). - ISSN 1618-2642 - p. 1111 - 1122.
    In oral bioavailability studies, evaluation of the absorption and transport of drugs and food components across the intestinal barrier is crucial. Advances in the field of organ-on-a-chip technology have resulted in a dynamic gut-on-a-chip model that better mimics the in vivo microenvironment of the intestine. Despite a few recent integration attempts, ensuring a biologically relevant microenvironment while coupling with a fully online detection system still represents a major challenge. Herein, we designed an online technique to measure drug permeability and analyse unknown product formation across an intestinal epithelial layer of Caco-2 and HT29-MTX cells cultured on a flow-through Transwell system, while ensuring the quality and relevance of the biological model. Chip-based ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was coupled to the dynamic Transwell system via a series of switching valves, thus allowing alternating measurements of the apical and basolateral sides of the in vitro model. Two trap columns were integrated for online sample pre-treatment and compatibility enhancement. Temporal analysis of the intestinal permeability was successfully demonstrated using verapamil as a model drug and ergotamine epimers as a model for natural toxins present in foods. Evidence was obtained that our newly developed dynamic system provided reliable results versus classical static in vitro models, and moreover, for the first time, epimer-specific transport is shown for ergotamine. Finally, initial experiments with the drug granisetron suggest that metabolic activity can be studied as well, thus highlighting the versatility of the bio-integrated online analysis system developed.
    Current insights in monitoring, bioaccumulation, and potential health effects of microplastics present in the food chain
    Raamsdonk, L.D.W. van; Zande, M. van der; Koelmans, A.A. ; Hoogenboom, R.L.A.P. ; Peters, R.J.B. ; Groot, M.J. ; Peijnenburg, A.C.M. ; Weesepoel, Y.J.A. - \ 2020
    Foods 9 (2020)1. - ISSN 2304-8158
    Microplastics (MPs) are considered an emerging issue as environmental pollutants and a potential health threat. This review will focus on recently published data on concentrations in food, possible effects, and monitoring methods. Some data are available on concentrations in seafood (fish, bivalves, and shrimps), water, sugar, salt, and honey, but are lacking for other foods. Bottled water is a considerable source with numbers varying between 2600 and 6300 MPs per liter. Particle size distributions have revealed an abundance of particles smaller than 25 µm, which are considered to have the highest probability to pass the intestinal border and to enter the systemic circulation of mammals. Some studies with mice and zebrafish with short- or medium-term exposure (up to 42 days) have revealed diverse results with respect to both the type and extent of effects. Most notable modifications have been observed in gut microbiota, lipid metabolism, and oxidative stress. The principal elements of MP monitoring in food are sample preparation, detection, and identification. Identified data gaps include a lack of occurrence data in plant- and animal-derived food, a need for more data on possible effects of different types of microplastics, a lack of in silico models, a lack of harmonized monitoring methods, and a further development of quality assurance.
    Spray drift of a two-row tunnel orchard sprayer
    Zande, J.C. van de; Michielsen, J.G.P. ; Snoussi, Mostafa ; Stallinga, H. ; Hoog, Dirk de; Dalfsen, P. van; Wenneker, M. - \ 2019
    In: Suprofruit2019 – 15th Workshop on Spray Application and Precision Technology in Fruit Growing, July 16-18, 2019, NIAB EMR, East Malling, UK. 2019. p. 90-91 / Cross, J., Wenneker, M., NIAB EMR - ISBN 9789463950206 - p. 89 - 90.
    Spray drift of a two-row tunnel orchard sprayer
    Zande, Jan van de - \ 2019
    Automated blossom detection for precision fruit farming
    Hoog, Dirk de; Afonso, M.V. ; Zande, J.C. van de - \ 2019
    Spray deposition of a cross-flow fan orchard sprayer with low air and low spray pressure settings
    Michielsen, J.G.P. ; Stallinga, H. ; Hoog, Dirk de; Dalfsen, P. van; Wenneker, M. ; Zande, J.C. van de - \ 2019
    In: SuproFruit 2019 – 15th Workshop on Spray Application and Precision Technology in Fruit Growing / Cross, J., Wenneker, M., NIAB EMR - ISBN 9789463950206 - p. 47 - 48.
    Automated blossom detection for precision fruit farming
    Hoog, Dirk de; Afonso, Manya ; Zande, Jan van de - \ 2019
    A probabilistic approach to exposure assessment for downwind deposits of spray drift
    Holterman, H.J. ; Zande, Jan van de - \ 2019
    - p. 289 - 289.
    Deposition of spray drift onto surface waters is a major cause for the risk of exposure to pesticides for aquatic organisms. This risk is particularly high for surface waters alongside pome fruit orchards, where pesticide sprays are applied in a sideways or an upward direction. Recently a spray drift model has been developed to estimate pesticide deposits onto downwind off-target areas next to fruit orchards. Using this spray drift model, an exposure assessment model has been developed to estimate risk of exposure to pesticides for aquatic organisms in edge-of-field watercourses next to pome fruit orchards in the Netherlands. For arable crops, typically, the risk of exposure is much less, considering pesticide concentrations in the edge-of-field watercourse. However, the total area for arable crops is much higher than that for fruit orchards. This paper describes the probabilistic processes concerning the countrywide risk assessment using a exposure model for one field and one ditch. Spatial and temporal variables are distinguished. Spatial variables include regional distributions of orchards and different types of watercourses, various water levels and continuously varying growth stages during the year. Temporal variables include frequency distributions of wind speed and direction and ambient temperature. 90% risk levels of predicted environmental concentrations (PEC) in surface water can be determined for various spray application schemes including multiple spray applications during a year. In an extensive simulation study the PECs in the watercourses were computed for all possible spatial configurations. A spatio-temporal statistical analysis on these simulations resulted in a quantitative risk assessment for a representative set of spray application schemes. Various model features (including drift mitigation, crop-free zones) result in a versatile exposure assessment model with a high level of realism. The spray drift deposits onto the water surface can be used as input for models describing the fate of pesticides in the watercourses. In this way, a realistic simulation study on the exposure to and fate of pesticides in surface waters can be performed to quantify exposure risk levels for aquatic organisms. The countrywide exposure risk model supports higher-tier assessment studies for the authorization of plant protection products.
    Human gut-on-a-chip as a predictive model for compound bio availability and toxicity
    Zande, M. van der; Kulthong, K. ; Duivenvoorde, L.P.M. ; Rijkers, Deborah ; Grouls, M. ; Haan, L.H.J. de; Bouwmeester, H. - \ 2019
    Spray drift for the assessment of exposure of aquatic organisms to plant protection products in the Netherlands : Part 2: Sideways and upward sprayed fruit and tree crops
    Zande, J.C. van de; Holterman, H.J. ; Huijsmans, J.F.M. ; Wenneker, M. - \ 2019
    Wageningen : Stichting Wageningen Research, Wageningen Plant Research, Business Unit Agrosystems Research (Report / Stichting Wageningen Research, Wageningen Plant Research, Business Unit Agrosystems Research WPR-564) - 85
    As part of the Dutch authorisation procedure for pesticides an assessment of the effects on aquatic organisms in surface water adjacent to agricultural fields is required. This in turn requires an exposure assessment for these surface waters. So far, in the current Dutch authorisation procedure spray drift is the only source of exposure. For this reason, a new exposure scenario was developed, which includes also input by drainage and atmospheric deposition. The endpoint of the exposure assessment is the 90th percentile of the annual maximum concentration in all field ditches alongside fruit and avenue nursery-tree fields. In this report, the state-of-the-art of the spray drift data is described for orchard spraying and avenuenursery-tree spraying. The methodology of using a matrix structure is discussed for the assessment of spray drift deposition combining classes of Drift Reducing Technology (DRT) and width of crop free zones for sideways and upward sprayed crops (fruit crops and avenue nursery-trees). Key words: spray drift, air -blast sprayer, Drift Reduction Technology, ISO22866, surface water, crop free zone, orchard spraying, avenue nursery tree spraying.
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