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Stevens, L.J. (author), Zhu, A.Z.X. (author), Chothe, P.P. (author), Chowdhury, S.K. (author), Donkers, J.M. (author), Vaes, W.H.J. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion and plasma exposure of drugs. For this evaluation we dosed...article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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Gozalpour, E. (author), Greupink, R. (author), Wortelboer, H.M. (author), Bilos, A. (author), Schreurs, M. (author), Russel, F.G.M. (author), Koenderink, J.B. (author)Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters...article 2014
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van Boxtel, E.L. (author), van den Broek, L.A.M. (author), Koppelman, S.J. (author), Vincken, J.-P. (author), Gruppen, H. (author), TNO Kwaliteit van Leven (author)Mildly extracted peanut allergen Ara h 1 was previously reported to occur as an oligomeric complex. In this paper we describe how the protein in this oligomeric complex interacts noncovalently with phenolic compounds of the proanthocyanidin type. These interactions are being disrupted during anion exchange chromatography, resulting in the...article 2007
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Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...article 2007
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Ullmann, U. (author), Haller, J. (author), Bakker, G.C.M. (author), Brink, E.J. (author), Weber, P. (author), TNO Kwaliteit van Leven (author)A number of studies have shown that tea catechins can inhibit intestinal iron absorption, mostly iron in the nonhaem form. This randomized, double-blind, placebo-controlled, 3-periods cross-over study examined the degree of inhibition of nonhaem iron absorption by pure crystalline epigallocatechin gallate (EGCG). The study was designed to show...article 2005
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Jonker, D. (author), Freidig, A.P. (author), Groten, J.P. (author), de Hollander, A.E.M. (author), Stierum, R.H. (author), Woutersen, R.A. (author), Feron, V.J. (author), TNO Voeding (author)Recent developments in hazard identification and risk assessment of chemical mixtures are reviewed. Empirical, descriptive approaches to study and characterize the toxicity of mixtures have dominated during the past two decades, but an increasing number of mechanistic approaches have made their entry into mixture toxicology. A series of...article 2004
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- Ommen, B. (author), Groten, J.P. (author), TNO Voeding (author) article 2004
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Prigent, S.V.E. (author), Gruppen, H. (author), Visser, A.J.W.G. (author), van Koningsveld, G.A. (author), de Jong, G.A.H. (author), Voragen, A.G.J. (author)The non-covalent interactions between the monomeric phenolic compound chlorogenic acid (5-CQA) and bovine serum albumin (BSA), lysozyme, and α-lactalbumin were characterized, and their effect on protein properties was examined. 5-CQA had a low affinity for all three proteins, and these interactions seemed to show a negative cooperativity. 5-CQA...article 2003
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Feron, V.J. (author), Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures have gradually substituted trial-and-error...article 2002
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Renwick, A.B. (author), Ball, S.E. (author), Tredger, J.M. (author), Price, R.J. (author), Walters, D.G. (author), Kao, J. (author), Scatina, J.A. (author), Lake, B.G. (author), TNO Voeding (author)The effect of cimetidine on the metabolism of zaleplon (ZAL) in human liver subcellular fractions and precision-cut liver slices was investigated. 2. ZAL was metabolized to a number of products including 5-oxo-ZAL (M2), which is known to be formed by aldehyde oxidase, N-desethyl-ZAL (DZAL), which is known to be formed by CYP3A forms, and N...article 2002
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Feron, V.J. (author), Cassee, F.R. (author), Groten, J.P. (author), van Vliet, P.W. (author), van Zorge, J.A. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)In this article, we highlight new developments and recent studies concerning adverse human health effects related to chemical mixtures. One group of activities comprises the development of a new computer program for analyzing mixture studies and a mathematical model as a basis for combination rules that predict the toxicity of mixtures. Other...article 2002
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van der Heijden, P.G.M. (author), van Puijenbroek, E.P. (author), van Buuren, S. (author), van der Hofstede, J.W. (author)A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting odds ratios. We will show that certain under...article 2002
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Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Drinking water can be considered as a complex mixture that consists of tens, hundreds or thousands of chemicals of which the composition is qualitatively and quantitatively not fully known. From a public health point of view it is most relevant to answer the question of whether chemicals in drinking water interact in a way that results in an...article 2000
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Bogaards, J.J.P. (author), Hissink, E.M. (author), Briggs, M. (author), Weaver, R. (author), Jochemsen, R. (author), Jackson, P. (author), Bertrand, M. (author), van Bladeren, P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the...article 2000
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Groten, J.P. (author), Butler, W. (author), Feron, V.J. (author), Kozianowski, G. (author), Renwick, A.G. (author), Walker, R. (author)The possibility that structurally unrelated food additives could show either joint actions or interactions has been assessed based on their potential to share common sites and mechanisms of action or common pathways of elimination. All food additives approved in the European Union and allocated numerical acceptable daily intake values were...article 2000
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van de Vijver, L.P.L. (author), Kardinaal, A.F.M. (author), Charzewska, J. (author), Rotily, M. (author), Charles, P. (author), Maggiolini, M. (author), Ando, S. (author), Väänänen, K. (author), Wajszczyk, B. (author), Heikkinen, J. (author), Deloraine, A. (author), Schaafsma, G. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Several studies indicate that intake of calcium can inhibit iron absorption especially when taken simultaneously. In the CALEUR study, a cross-sectional study among girls (mean 13.5 y) and young women (mean 22.0 y) in six European countries, the association between calcium intake and iron status was studied. In 1,080 girls and 524 women,...article 1999
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Woutersen, R.A. (author), Wolterbeek, A.P.M. (author), Appel, M.J. (author), van den Berg, H. (author), Goldbohm, R.A. (author), Feron, V.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The safety of β-carotene was reassessed by evaluating the relevant literature on the beneficial and adverse effects of β-carotene on cancer and, in particular, by evaluating the results of toxicity studies. β- Carotene appeared neither genotoxic nor reprotoxic or teratogenic, and no signs of organ toxicity have been found in subacute, subchronic...article 1999
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van den Berg, H. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)Chemicals/CAS: Carotenoids, 36-88-4; Chylomicronsarticle 1999
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Feron, V.J. (author), Cassee, F.R. (author), Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)This paper reviews major activities outside the United States on human health issues related to chemical mixtures. In Europe an international study group on combination effects has been formed and has started by defining synergism and antagonism. Successful research programs in Europe include the development and application of statistically...article 1998