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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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Woutersen, R.A. (author), Soffers, A.E.M.F. (author), Kroese, E.D. (author), Krul, C.A.M. (author), van der Laan, J.W. (author), van Benthem, J. (author), Luijten, M. (author)Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the...article 2016
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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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van der Laan, J.W. (author), Buitenhuis, W.H.W. (author), Wagenaar, L. (author), Soffers, A.E.M.F. (author), van Someren, E.P. (author), Krul, C.A.M. (author), Woutersen, R.A. (author)In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for...article 2016
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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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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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Kleinnijenhuis, A.J. (author), Staal, Y.C.M. (author), Duistermaat, E. (author), Engel, R. (author), Woutersen, R.A. (author)Formaldehyde (FA) is suspected of being associated with the development of leukemia. An inhalation experiment with FA was performed in rats to study whether FA can enter the blood and could thus cause systemic toxicity in remote tissues such as the bone marrow. Therefore, a sophisticated analytical method was developed to detect blood...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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Kuper, C.F. (author), van Oostrum, L. (author), Ma-Hock, L. (author), Durrer, S. (author), Woutersen, R.A. (author)To investigate if local lymphoid tissues are a target of FA, nasopharynx-associated lymphoid tissues (NALT) and upper-respiratory tract-draining lymph nodes were examined in a 28-day inhalation study with FA vapor in Fischer-344 rats and B6C3F1 mice.Paraffin-embedded tissues were sectioned and stained with H&E or stained immunohistochemically...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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van Triel, J.J. (author), van Bree, B.W.J. (author), Roberts, D.W. (author), Muijser, H. (author), Duistermaat, E. (author), Woutersen, R.A. (author), Kuper, C.F. (author)Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen...article 2011
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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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Woutersen, R.A. (author), Slootweg, P.J. (author), Kuper, C.F. (author), TNO Kwaliteit van Leven (author)Inhalation toxicity testing is becoming increasingly important, among other things because of the increasing number of drugs that are administered through the intranasal route to avoid enzymatic and acid breakdown and first pass metabolism in the gastrointestinal mucosa and the liver. The nature and site of damage to the nasal mucosa are...conference paper 2010
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de Jong, E. (author), Louisse, J. (author), Verwei, M. (author), Blaauboer, B.J. (author), van de Sandt, J.J.M. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Piersma, A.H. (author), TNO Kwaliteit van Leven (author)The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness...article 2009
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Dihal, A.A. (author), van der Woude, H. (author), Hendriksen, P.J.M. (author), Charif, H. (author), Dekker, L.J. (author), IJsselstijn, L. (author), de Boer, V.C.J. (author), Alink, G.M. (author), Burgers, P.C. (author), Rietjens, I.M.C.M. (author), Woutersen, R.A. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author), KvL (author)Quercetin has been shown to act as an anticarcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterize transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 wk. Transcriptome data analyzed with Gene Set Enrichment Analysis showed...article 2008