- document
-
Beker van Woudenberg, A. (author), Wolterbeek, A. (author), te Brake, L. (author), Snel, C. (author), Menke, A. (author), Rubingh, C. (author), de Groot, D. (author), Kroese, D. (author)Zebrafish embryos were exposed to different organotin compounds during very early development (<100. h post fertilization). Morphology, histopathology and swimming activity (in a motor activity test) were the endpoints analyzed. DBTC was, by far, the most embryotoxic compound at all time points and endpoints studied. In fact, we observed a clear...article 2013
- document
-
Krishnan, S. (author), Verheij, E.E.R. (author), Bas, R.C. (author), Hendriks, M.W.B. (author), Hankemeier, T. (author), Thissen, U. (author), Coulier, L. (author)RATIONALE Mass spectra obtained by deconvolution of liquid chromatography/high-resolution mass spectrometry (LC/HRMS) data can be impaired by non-informative mass-over-charge (m/z) channels. This impairment of mass spectra can have significant negative influence on further post-processing, like quantification and identification. METHODS A metric...article 2013
- document
-
Buist, H. (author), Aldenberg, T. (author), Batke, M. (author), Escher, S. (author), Kühne, R. (author), Marquart, H. (author), Pauné, E. (author), Rorije, E. (author), Schüürmann, G. (author), Kroese, D.E. (author)Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on 31 their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for rel- 32 evant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This 33 paper describes the...article 2013
- document
-
Leeman, W.R. (author), Krul, L. (author), Houben, G.F. (author)Upon analysis of chemically complex food matrices a forest of peaks is likely to be found. Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies. Recently, a safety assessment framework based on the Threshold of Toxicological...article 2013
- document
-
Tonk, E.C.M. (author), de Groot, D.M.G. (author), Wolterbeek, A.P.M. (author), Penninks, A.H. (author), Waalkens-Berendsen, I.D.H. (author), Piersma, A.H. (author), van Loveren, H. (author)The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of...article 2013
- document
-
Marvin, H.J.P. (author), Bouwmeester, H. (author), Bakker, M. (author), Kroese, E.D. (author), van de Meent, D. (author), Bourgeois, F. (author), Lokers, R. (author), van der Ham, H. (author), Verhelst, L. (author)Engineered nanoparticles (ENPs) have gained huge commercial interest because of their unique and size-related physicochemical properties. The diversity and complexity of ENPs is increasing with the introduction of next generation nanoparticles. The current approaches are not able to assess the safety of all types and applications of ENPs....article 2013
- document
-
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
- document
-
Radonjic, M. (author), Cappaert, N.L.M. (author), de Vries, E.F.J. (author), de Esch, C.E.F. (author), Kuper, F.C. (author), van Waarde, A. (author), Dierckx, R.A.J.O. (author), Wadman, W.J. (author), Wolterbeek, A.P.M. (author), Stierum, R.H. (author), de Groot, D.M.G. (author)Maternal exposure to the neurotoxin methylmercury (MeHg) has been shown to have adverse effects on neural development of the offspring in man. Little is known about the underlying mechanisms by which MeHg affects the developing brain. To explore the neurodevelopmental defects and the underlying mechanism associated with MeHg exposure, the...article 2013
- document
-
van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Kuper, C.F. (author), Wolthoorn, J. (author), van Meeteren-Kreikamp, A.P. (author), Nagtegaal, M.M. (author), Doornbos, R. (author), Ganderup, N.-C. (author), Penninks, A.H. (author)The use of recombinant human proteins for the treatment of several diseases has increased considerably during the last decades. A major safety and efficacy issue of biopharmaceuticals is their potential immunogenicity. To prevent immunogenicity, biotechnology-derived proteins are engineered to be as human-like as possible. Immunogenicity is...article 2013
- document
-
Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networksPronk, T.E. (author), van Someren, P. (author), Stierum, R.H. (author), Ezendam, J. (author), Pennings, J.L.A. (author)The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in...article 2013
- document
-
van den Broek, I. (author), Niessen, W.M.A. (author), van Dongen, W.D. (author)Biotechnology increasingly delivers highly promising protein-based biopharmaceutical candidates to the drug development funnel. For successful biopharmaceutical drug development, reliable bioanalytical methods enabling quantification of drugs in biological fluids (plasma, urine, tissue, etc.) are required to generate toxicokinetic (TK),...article 2013
- document
- Sauerborn, M. (author) article 2013
- document
-
Destexhe, E. (author), Prinsen, M.K. (author), van Schöll, I. (author), Kuper, C.F. (author), Garçon, N. (author), Veenstra, S. (author), Segal, L. (author)Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma protein of hepatic origin that could be used for...article 2013
- document
-
Vermeire, T. (author), Aldenberg, T. (author), Buist, H. (author), Escher, S. (author), Mangelsdorf, I. (author), Pauné, E. (author), Rorije, E. (author), Kroese, D.E. (author)Chemical substances policies in Europe are aiming towards chemical safety and at the same time a reduction in animal testing. These goals are alleged to be reachable by mining as many relevant data as possible, evaluate these data with regard to validity, reliability and relevance, and use of these data in so-called Integrated Testing Strategies...article 2013
- document
-
van Mierlo, G.J.D. (author), Kuper, C.F. (author), de Zeeuw-Brouwer, M.L. (author), Schijf, M.A. (author), Bruijntjes, J.P. (author), Otto, M. (author), Ganderup, N.C. (author), Penninks, A.H. (author)Introduction: There is a growing interest in the minipig as a non-rodent species in the safety assessment of (bio) pharmaceuticals and (agro) chemicals. For (bio) pharmaceuticals the need to evaluate the potential adverse effects on the immune system is an increasingly important aspect of safety evaluation. In the present study, cyclosporin A...article 2013
- document
-
Radonjic, M. (author), Wielinga, P.Y. (author), Wopereis, S. (author), Kelder, T. (author), Goelela, V.S. (author), Verschuren, L. (author), Toet, K. (author), van Duyvenvoorde, W. (author), van der Werff van der Vat, B. (author), Stroeve, J.H.M. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM). Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of...article 2013
- document
- van der Schans, M.J. (author), Noort, D. (author), Fidder, A. (author), Hulst, A.G. (author) conference paper 2012
- document
-
van Hulst, M. (author), Langenberg, J.P. (author), Alblas, M. (author)Particle matter (PM) <10 μm is known to be unhealthy. Sand present in some of the expeditionary areas military personal is stationed contains diverse particles sizes including the PM< 10 μm. When Smoke ammunition is used it might be possible that the formed smoke components are adsorbed by these small sand particle and when the are inhaled cause...conference paper 2012
- document
-
van Dongen, W.D. (author), Niessen, W.M.A. (author)LC-MS has become the method-of-choice in small-molecule drug bioanalysis (molecular mass <800 Da) and is also increasingly being applied as an alternative to ligand-binding assays for the bioanalytical determination of biopharmaceuticals. Triple quadrupole MS is the established bioanalytical technique due to its unpreceded selectivity and...article 2012
- document
- Noort, D. (author), van der Schans, M.J. (author) conference paper 2012