- document
-
Wambaugh, J.F. (author), Hughes, M.F. (author), Ring, C.L. (author), MacMillan, D.K. (author), Ford, J. (author), Fennell, T.R. (author), Black, S.R. (author), Snyder, R.W. (author), Sipes, N.S. (author), Wetmore, B.A. (author), Westerhout, J. (author), Setzer, R.W. (author), Pearce, R.G. (author), Simmons, J.E. (author), Thomas, R.S. (author)Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo...article 2018
- document
-
Botschuijver, S. (author), Welting, O. (author), Levin, E. (author), Maria-Ferreira, D. (author), Koch, E. (author), Montijn, R.C. (author), Seppen, J. (author), Hakvoort, T.B.M. (author), Schuren, F.H.J. (author), de Jonge, W.J. (author), van den Wijngaard, R.M. (author)Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder associated with altered gastrointestinal microflora and increased nociception to colonic distension. This visceral hypersensitivity can be reversed in our rat maternal separation model by fungicides. Menthacarin® is a proprietary combination of essential oils from...article 2018
- document
-
van Hulst, M. (author), Langenberg, J.P. (author), de Klerk, W.P.C. (author), Alblas, M.J. (author)The toxicity of smoke-generating ammunition can be established by looking at the complete hand grenade or only at the smoke composition. In this paper both approaches are described. The toxicity of a signalling smoke was assessed as a complete smoke hand grenade whereas for a 76 mm screening smoke canister only a red phosphorus (RP) pellet was...article 2017
- document
-
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
- document
-
Raaphorst, R.M. (author), Savolainen, H. (author), Cantore, M. (author), van de Steeg, E. (author), van Waarde, A. (author), Colabufo, N.A. (author), Elsinga, P.H. (author), Lammertsma, A.A. (author), Windhorst, A.D. (author), Luurtsema, G. (author)Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...article 2017
- document
-
Colaianna, M. (author), Ilmjärv, S. (author), Peterson, H. (author), Ilse Kern, I. (author), Julien, S. (author), Baquié, M. (author), allocca, G. (author), Bosgra, S. (author), Sachinidis, A. (author), Hengstler, J.G. (author), Leist, M. (author), Krause, K.H. (author)Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim of this study was to develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell line CGR8 (ESCs). The test system uses ESCs at...article 2017
- document
-
Meuken, D. (author), van Lingen, J.N.J. (author), Polk-LaBonte, A. (author), Domanico, J. (author)A significant health and possibly environmental problem is associated with military smokes and obscurants. Besides the fact that these obscuration munitions pose a significant toxicity hazard to the user, the environmental impact of these munitions can also be significant (e.g. due to the use of hexachlorethane). The objective of the SERDP...conference paper 2016
- document
-
Koenen, M.E. (author), Cruz Rubio, J.M. (author), Mueller, M. (author), Venema, K. (author)Inulin and trans-galactooligosaccharides have so far fully met the criteria for prebiotics. This study shows the effect of putative prebiotics Metlos and Metlin (short and medium chain branched fructans from agave) on the activity and composition of the gut microbiota compared to the effects of two linear inulin type fructans (Synergy1 and...article 2016
- document
-
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
- document
-
Aguirre, M. (author), Eck, A. (author), Koenen, M.E. (author), Savelkoul, P.H.M. (author), Budding, A.E. (author), Venema, K. (author)The aim of this study was to screen how rapidly the human gut microbiota responds to diet in an in vitro model of the proximal colon (TIM-system). Two experimental diets were provided to the gut bacteria: a high carbohydrate and a high protein diet. The metabolic response and the composition of the microbiota were compared to a control diet...article 2016
- document
-
Janus, M.M. (author), Crielaard, W. (author), Zaura, E. (author), Keijser, B.J. (author), Brandt, B.W. (author), Krom, B.P. (author)Objective: Dental caries is caused by prolonged episodes of low pH due to acid production by oral biofilms. Bacteria within such biofilms communicate via quorum sensing (QS). QS regulates several phenotypic biofilm parameters, such as biofilm formation and the production of virulence factors. In this study, we evaluated the effect of several QS...article 2016
- document
-
Kortman, G.A.M. (author), Dutilh, B.E. (author), Maathuis, A.J.H. (author), Engelke, U.F. (author), Boekhorst, J. (author), Keegan, K.P. (author), Nielsen, F.G.G. (author), Betley, J. (author), Weir, J.C. (author), Kingsbury, Z. (author), Kluijtmans, L.A.J. (author), Swinkels, D.W. (author), Venema, K. (author), Tjalsma, H. (author)Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The...article 2016
- document
-
Verwei, M. (author), Minekus, M. (author), Zeijdner, E. (author), Schilderink, R. (author), Havenaar, R. (author)Pharmaceutical research needs predictive in vitro tools for API bioavailability in humans. We evaluated two dynamic in vitro gastrointestinal models: TIM-1 and tiny-TIM. Four low-soluble APIs in various formulations were investigated in the TIM systems under fasted and fed conditions. API small-intestinal bioaccessibility profiles were evaluated...article 2016
- document
-
Dusinska, M. (author), Boland, S. (author), Saunders, M. (author), Juillerat-Jeanneret, L. (author), Tran, L. (author), Pojana, G. (author), Marcomini, A. (author), Volkovova, K. (author), Tulinska, J. (author), Knudsen, L.E. (author), Gombau, L. (author), Whelan, M. (author), Collins, A.R. (author), Marano, F. (author), Housiadas, C. (author), Bilanicova, D. (author), Halamoda Kenzaoui, B. (author), Correia Carreira, S. (author), Magdolenova, Z. (author), Fjellsbo, L.M. (author), Huk, A. (author), Handy, R. (author), Walker, L. (author), Barancokova, M. (author), Bartonova, A. (author), Burello, E. (author), Castell, J. (author), Cowie, H. (author), Drlickova, M. (author), Guadagnini, R. (author), Harris, G. (author), Harju, M. (author), Heimstad, E.S. (author), Hurbankova, M. (author), Kazimirova, A. (author), Kovacikova, Z. (author), Kuricova, M. (author), Liskova, A. (author), Milcamps, A. (author), Neubauerova, E. (author), Palosaari, T. (author), Papazafiri, P. (author), Pilou, M. (author), Poulsen, M.S. (author), Ross, B. (author), Runden-Pran, E. (author), Sebekova, K. (author), Staruchova, M. (author), Vallotto, D. (author), Worth, A. (author)In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about...article 2015
- document
-
Higuera, G.A. (author), Fernandes, H. (author), Spitters, T.W.G.M. (author), van de Peppel, J. (author), Aufferman, N. (author), Truckenmueller, R. (author), Stoop, R. (author), van Leeuwen, J.P. (author), de Boer, J. (author), Subramaniam, V. (author), Karperien, M. (author), van Blitterswijk, C. (author), van Boxtel, A. (author), Moroni, L. (author)Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results...article 2015
- document
-
Reinen, J. (author), Nematollahi, L. (author), Fidder, A. (author), Vermeulen, N.P.E. (author), Noort, D. (author), Commandeur, J.N.M. (author)Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can...article 2015
- document
-
Bosgra, S. (author), Westerhout, J. (author)In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and observations of developmental toxicity in vivo....article 2015
- document
-
Janus, M.M. (author), Keijser, B.J.F. (author), Bikker, F.J. (author), Exterkate, R.A.M. (author), Crielaard, W. (author), Krom, B.P. (author)Commensal oral biofilms, defined by the absence of pathology-related phenotypes, are ubiquitously present. In contrast to pathological biofilms commensal biofilms are rarely studied. Here, the effect of the initial inoculum and subsequent growth conditions on in vitro oral biofilms was studied. Biofilms were inoculated with saliva and grown...article 2015
- document
-
Johnson, D. (author), Carter, M.D. (author), Crow, B.S. (author), Isenberg, S.L. (author), Graham, L.A. (author), Erol, H.A. (author), Watson, C.M. (author), Pantazides, B.G. (author), van der Schans, M.J. (author), Langenberg, J.P. (author), Noort, D. (author), Blake, T.A. (author), Thomas, J.D. (author), Johnson, R.C. (author)Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including...article 2015
- document
-
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