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Moné, M.J. (author), Pallocca, G. (author), Escher, S.E. (author), Exner, T. (author), Herzler, M. (author), Hougaard Bennekou, S. (author), Kamp, H. (author), Kroese, E.D. (author), Leist, M. (author), Steger-Hartmann, T. (author), van de Water, B. (author)
In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain...
article 2020
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Luijten, M. (author), Olthof, E.D. (author), Hakkert, B.C. (author), Rorije, E. (author), van der Laan, J.-W. (author), Woutersen, R.A. (author), van Benthem, J. (author)
Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer...
article 2016
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Reus, A.A. (author), Usta, M. (author), Kenny, J.D. (author), Clements, P.J. (author), Pruimboom-Brees, I. (author), Aylott, M. (author), Lynch, A.M. (author), Krul, C.A.M. (author)
An in vivo photomicronucleus test (MNT) using rat skin, the target organ for photoirritancy and carcinogenicity, was recently described. The assay was evaluated using fluoroquinolone (FQ) antibiotics with varying degrees of phototoxic potency (i.e. sparflocacin [SPFX], lomefloxacin [LOFX], ciprofloxacin [CIFX], levofloxacin [LEFX], gemifloxacin ...
article 2012
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Berg, N. (author), de Wever, B. (author), Fuchs, H.W. (author), Gaca, M. (author), Krul, C.A.M. (author), Roggen, E.L. (author)
In November 2009 the In Vitro Testing Industrial Platform (IVTIP) organized a meeting entitled '. Toxicology in the 21st century - working our way towards a visionary reality'. Participating delegates included scientists, key opinion leaders, developers and users of 3Rs-related tests and testing strategies. This paper summarizes the discussions...
article 2011
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Vandebriel, R. (author), Callant Cransveld, C. (author), Crommelin, D. (author), Diamant, Z. (author), Glazenburg, B. (author), Joos, G. (author), Kuper, F. (author), Natsch, A. (author), Nijkamp, F. (author), Noteborn, H. (author), Pieters, R. (author), Roberts, D. (author), Roggen, E. (author), Rorije, E. (author), Seed, M. (author), Sewald, K. (author), van den Heuvel, R. (author), van Engelen, J. (author), Verstraelen, S. (author), van Loveren, H. (author)
Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to...
article 2011
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van de Briel, R.J. (author), Pennings, J.L.A. (author), Baken, K.A. (author), Pronk, T.E. (author), Boorsma, A. (author), Gottschalk, R. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)
Many chemicals can induce allergic contact dermatitis. Because evaluation of skin sensitizing potential by animal testing is prohibited for cosmetics, and screening of many chemicals is required within Registration, Evaluation, Authorisation and Restriction of Chemicals, urgent need exists for predictive in vitro assays to identify contact...
article 2010
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de Leeuw van Weenen, J.E. (author), Parlevliet, E.T. (author), Maechler, P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Pijl, H. (author), Guigas, B. (author), TNO Kwaliteit van Leven (author)
Treatment with the dopamine receptor D2 (DRD2) agonist bromocriptine improves metabolic features in obese patients with type 2 diabetes by a still unknown mechanism. In the present study, we investigated the acute effect of bromocriptine and its underlying mechanism(s) on insulin secretion both in vivo and in vitro. For this purpose, C57Bl6/J...
article 2010
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Hamer, H.M. (author), Jonkers, D.M.A.E. (author), Renes, I.B. (author), Vanhoutvin, S.A.L.W. (author), Kodde, A. (author), Troost, F.J. (author), Venema, K. (author), Brummer, R.-J.M. (author), TNO Kwaliteit van Leven (author)
INTRODUCTION: The colonic mucus layer plays an important role in the protection of the intestinal epithelium and mainly consists of mucin glycoproteins (primarily MUC2 in the colon) trefoil factor 3 (TFF3) and secretory IgA. Butyrate is a major end product of fermentation of dietary fibres and is associated with beneficial effects on colonic...
article 2010
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Eefting, D. (author), Bot, I. (author), de Vries, M.R. (author), Schepers, A. (author), van Bockel, J.H. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)
Objective: Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the...
article 2009
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Buist, H.E. (author), Schaafsma, G. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)
Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual...
article 2009
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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...
article 2009
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Schutte, K. (author), Prinsen, M.K. (author), McNamee, P.M. (author), Roggeband, R. (author), TNO Kwaliteit van Leven (author)
Eye irritation is an important endpoint in the safety evaluation of consumer products and their ingredients. Several in vitro methods have been developed and are used by different industry sectors to assess eye irritation. One such in vitro method in use for some time already is the isolated chicken eye test (ICE). This investigation focuses on...
article 2009
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Parker, A.L. (author), Waddington, S.N. (author), Buckley, S.M.K. (author), Custers, J. (author), Havenga, M.J.E. (author), van Rooijen, N. (author), Goudsmit, J. (author), McVey, J.H. (author), Nicklin, S.A. (author), Baker, A.H. (author), TNO Kwaliteit van Leven (author)
The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based...
article 2009
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Ponstein-Simarro Doorten, A.Y. (author), van de Wiel, J.A.G. (author), Jonker, D. (author), TNO Kwaliteit van Leven (author)
Tensguard™ is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard™ product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to...
article 2009
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Kovatcheva-Datchary, P. (author), Egert, M. (author), Maathuis, A. (author), Rajilić-Stojanović, M. (author), de Graaf, A.A. (author), Smidt, H. (author), de Vos, W.M. (author), Venema, K. (author), TNO Kwaliteit van Leven (author)
Summary Carbohydrates, including starches, are an important energy source for humans, and are known for their interactions with the microbiota in the digestive tract. Largely, those interactions are thought to promote human health. Using 16S ribosomal RNA (rRNA)-based stable isotope probing (SIP), we identified starch-fermenting bacteria under...
article 2009
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Rijken, D.C. (author), Hoegee-de Nobel, E. (author), Jie, A.F.H. (author), Atsma, D.E. (author), Schalij, M.J. (author), Nieuwenhuizen, W. (author), TNO Kwaliteit van Leven (author)
Background: The development of global tests for the fibrinolytic capacity in blood is hampered by the low base-line fibrinolytic activity in blood, by the involvement of both plasmatic components and blood cells in the fibrinolytic system and by the loss of fibrinolytic activity as a result of the action of plasminogen activator inhibitor-1 (PAI...
article 2008
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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)
This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...
article 2008
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Vinken, M. (author), Doktorova, T. (author), Ellinger-Ziegelbauer, H. (author), Ahr, H.-J. (author), Lock, E. (author), Carmichael, P. (author), Roggen, E. (author), van Delft, J. (author), Kleinjans, J. (author), Castell, J. (author), Bort, R. (author), Donato, T. (author), Ryan, M. (author), Corvi, R. (author), Keun, H. (author), Ebbels, T. (author), Athersuch, T. (author), Sansone, S.-A. (author), Rocca-Serra, P. (author), Stierum, R. (author), Jennings, P. (author), Pfaller, W. (author), Gmuender, H. (author), Vanhaecke, T. (author), Rogiers, V. (author), TNO Kwaliteit van Leven (author)
Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing...
article 2008
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Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)
Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...
article 2008
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Sier, C.F.M. (author), Hawinkels, L.J.A.C. (author), Zijlmans, H.J.M.A.A. (author), Zuidwijk, K. (author), Muller, E.S.M. (author), Ferreira, V. (author), Hanemaaijer, R. (author), Mulder-Stapel, A.A. (author), Kenter, G.G. (author), Verspaget, H.W. (author), Gorter, A. (author), TNO Kwaliteit van Leven (author)
Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These immunohistochemical data were confirmed by RT-PCR on VEGF...
article 2008
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