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Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated...article 2017
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Walczak, A.P. (author), Kramer, E. (author), Hendriksen, P.J.M. (author), Tromp, P. (author), Helsper, J.P.F.G. (author), van der Zande, M. (author), Rietjens, I.M.C.M. (author), Bouwmeester, H. (author)Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with mucus secreting HT29-MTX cells and a tri-culture...article 2015
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Walczak, A.P. (author), Hendriksen, P.J.M. (author), Woutersen, R.A. (author), van der Zande, M. (author), Undas, A.K. (author), Helsdingen, R. (author), van den Berg, H.H.J. (author), Rietjens, I.M.C.M. (author), Bouwmeester, H. (author)The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral,...article 2015
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Kloet, S.K. (author), Walczak, A.P. (author), Louisse, J. (author), van den Berg, H.H.J. (author), Bouwmeester, H. (author), Tromp, P. (author), Fokkink, R.G. (author), Rietjens, I.M.C.M. (author)To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell...article 2015
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Louisse, J. (author), Bosgra, S. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author), Verwei, M. (author)The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity data obtained from in vitro assays for risk...article 2015
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van der Ploeg, M.J.C. (author), Handy, R.D. (author), Waalewijn-Kool, P.L. (author), van den Berg, J.H.J. (author), Herrera Rivera, Z.E. (author), Bovenschen, J. (author), Molleman, B. (author), Baveco, J.M. (author), Tromp, P. (author), Peters, R.J.B. (author), Koopmans, G.F. (author), Rietjens, I.M.C.M. (author), van den Brink, N.W. (author)The impact of silver nanoparticles (AgNP; at 0mg Ag/kg, 1.5mg Ag/kg, 15.4mg Ag/kg, and 154mg Ag/kg soil) and silver nitrate (AgNO3; 15.4mg 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...article 2014
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van de Pas, N.C.A. (author), Rullmann, J.A.C. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL...article 2014
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Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse...article 2013
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Bhattacharjee, S. (author), Marcelis, A.T.M. (author), Zuilhof, H. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Alink, G.M. (author)Tri-block copolymer nanoparticles (TCNP) are increasingly utilized, especially in drug delivery and diagnostics platforms. From in vitro studies, surface charge was observed to influence the transport of TCNP across the Caco-2 monolayers grown on transwell inserts. The objective of this study was to investigate the influence of surface charge on...article 2013
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Strikwold, M. (author), Woutersen, R.A. (author), Spenkelink, B. (author), Punt, A. (author), Rietjens, I.M.C.M. (author)The applicability of the embryonic stem cell test (EST) as an alternative for in vivo embryotoxicity testing was evaluated for a series of five p-substituted phenols. To this purpose, the potency ranking for this class of compounds derived from the inhibition of cardiomyocyte differentiation in the EST was compared to in vivo embryotoxic potency...article 2012
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van de Pas, N.C.A. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was directly adapted from a PBK model for mice by...article 2012
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Louisse, J. (author), Verwei, M. (author), Woutersen, R.A. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author)Introduction: Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use in toxicological research. Therefore, relevant biomarkers for in vivo developmental toxicity in in vitro assays are needed. Areas covered: The...article 2012
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Punt, A. (author), Schiffelers, M.J.W.A. (author), Jean Horbach, G. (author), van de Sandt, J.J.M. (author), Groothuis, G.M.M. (author), Rietjens, I.M.C.M. (author), Blaauboer, B.J. (author)The present paper aims at identifying strategies to increase the impact and applicability of alternative testing strategies in risk assessment. To this end, a quantitative and qualitative literature evaluation was performed on (a) current research efforts in the development of in vitro methods aiming for alternatives to animal testing, (b) the...article 2011
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van de Pas, N.C.A. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)The LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) concentrations are determined by the activity of a complex network of reactions in several organs. Physiologically-based kinetic (PBK) computational models can be used to describe these different reactions in an integrated, quantitative manner. A PBK model to predict plasma cholesterol...article 2011
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Louisse, J. (author), Gönen, S. (author), Rietjens, I.M.C.M. (author), Verwei, M. (author)The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental toxicity. The results reveal that the potency ranking...article 2011
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Louisse, J. (author), Bai, Y. (author), Verwei, M. (author), van de Sandt, J.J.M. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA)...article 2010
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Louisse, J. (author), de Jong, E. (author), van de Sandt, J.J.M. (author), Blaauboer, B.J. (author), Woutersen, R.A. (author), Piersma, A.H. (author), Rietjens, I.M.C.M. (author), Verwei, M. (author), TNO Kwaliteit van Leven (author)At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells,...article 2010
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van de Pas, N.C.A. (author), Soffers, A.E.M.F. (author), Freidig, A.P. (author), van Ommen, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author), TNO Kwaliteit van Leven (author)Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define the scope of this model, it is essential to...article 2010
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- Adams, T.B. (author), Lucas Gavin, C. (author), Taylor, S.V. (author), Waddell, W.J. (author), Cohen, S.M. (author), Feron, V.J. (author), Goodman, J. (author), Rietjens, I.M.C.M. (author), Marnett, L.J. (author), Portoghese, P.S. (author), Smith, R.L. (author), TNO Kwaliteit van Leven (author) article 2009
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Vermeulen, M. (author), Boerboom, A.M.M.J.F. (author), Blankvoort, B.M.G. (author), Aarts, J.M.M.J.G. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Vaes, W.H.J. (author), TNO Kwaliteit van Leven (author)Isothiocyanates are electrophiles that are able to induce phase II biotransformation enzyme gene expression via an electrophile-responsive element (EpRE) in the gene regulatory region. To study the potency of different isothiocyanates to induce the expression of EpRE-regulated genes, a Hepa-1c1c7 luciferase reporter cell line was exposed to...article 2009