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van den Dries, M.A. (author), Guxens, M. (author), Spaan, S. (author), Ferguson, K.K. (author), Philips, E. (author), Santos, S. (author), Jaddoe, V.W.V. (author), Ghassabian, A. (author), Trasande, L. (author), Tiemeier, H. (author), Pronk, A. (author)BACKGROUND: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the...article 2020
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Brotzmann, K. (author), Wolterbeek, A. (author), Kroese, D. (author), Braunbeck, T. (author)Since teratogenicity testing in mammals is a particular challenge from an animal welfare perspective, there is a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected embryonic vertebrate in vivo model. The predictive power of zebrafish...article 2020
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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
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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
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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
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Beker van Woudenberg, A. (author), Snel, C. (author), Rijkmans, E. (author), de Groot, D. (author), Bouma, M. (author), Hermsen, S. (author), Piersma, A. (author), Menke, A. (author), Wolterbeek, A. (author)To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH)...article 2014
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Zimmer, B. (author), Pallocca, G. (author), Dreser, N. (author), Foerster, S. (author), Waldmann, T. (author), Westerhout, J. (author), Julien, S. (author), Krause, K.H. (author), van Thriel, C. (author), Hengstler, J.G. (author), Sachinidis, A. (author), Bosgra, S. (author), Leist, M. (author)Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test...article 2014
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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
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de Esch, C. (author), Slieker, R. (author), Wolterbeek, A. (author), Woutersen, R. (author), de Groot, D. (author)The zebrafish is a powerful toxicity model; biochemical assays can be combined with observations at a structural and functional level within one individual. This mini review summarises the potency of zebrafish as a model for developmental neurotoxicity screening, and its possibilities to investigate working mechanisms of toxicants. The use of...article 2012
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Breier, J.M. (author), Gassmann, K. (author), Kayser, R. (author), Stegeman, H. (author), de Groot, D. (author), Fritsche, E. (author), Shafer, T.J. (author), TNO Kwaliteit van Leven (author)In vitro, high-throughput methods have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramifications for the accuracy, predictivity and sensitivity of the screening...article 2010
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Joosen, M.J.A. (author), Jousma, E. (author), van den Boom, T.M. (author), Kuijpers, W.C. (author), Smit, A.B. (author), Lucassen, P.J. (author), van Helden, H.P.M. (author), TNO Defensie en Veiligheid (author)To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep–wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and...article 2009
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Hissink, A.M. (author), Kulig, B.M. (author), Kruse, J. (author), Freidig, A.P. (author), Verwei, M. (author), Muijser, H. (author), Lammers, J.H.C.M. (author), Mckee, R.H. (author), Owen, D.E. (author), Sweeney, L.M. (author), Salmon, F. (author), TNO Kwaliteit van Leven (author)This report describes a physiologically based pharmacokinetic model for cyclohexane and its use in comparing internal doses in rats and volunteers following inhalation exposures. Parameters describing saturable metabolism of cyclohexane are measured in rats and used along with experimentally determined partition coefficients. The model is...article 2009
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Lammers, J.H.C.M. (author), Emmen, H.H. (author), Muijser, H. (author), Hoogendijk, E.M.G. (author), McKee, R.H. (author), Owen, D.E. (author), Kulig, B.M. (author), TNO Kwaliteit van Leven (author)The neurobehavioral effects of inhaled cyclohexane in rats and humans are investigated to define relationships between internal doses and acute central nervous system effects. Rats are exposed for 3 consecutive days at target concentrations of 0, 1.4, 8, and 28 g/m3, 8 h/d. Measurements include standardized observational measures, spontaneous...article 2009
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Lammers, J.H.C.M. (author), Emmen, H.H. (author), Muijser, H. (author), Hoogendijk, E.M.G. (author), McKee, R.H. (author), Owen, D.E. (author), Kulig, B.M. (author), TNO Kwaliteit van Leven (author)To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in...article 2007
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Lammers, J.H.C.M. (author), van Asperen, J. (author), de Groot, D. (author), Rijcken, W.R.P. (author), TNO Kwaliteit van Leven (author)The toxicity of exposure by inhalation to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study the impact of the exposure scenario on the behavioural effects of the model solvent toluene in rats was investigated. Rats were exposed for 7.5 h to either a constant concentration or...article 2005
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de Groot, D.M.G. (author), Bos-Kuijpers, M.H.M. (author), Kaufmann, W.S.H. (author), Lammers, J.H.C.M. (author), O'Callaghan, J.P. (author), Pakkenberg, B. (author), Pelgrim, M.T.M. (author), Waalkens-Berendsen, I.D.H. (author), Waanders, M.M. (author), Gundersen, H.J.J. (author), TNO Kwaliteit van Leven (author)Our aim was to investigate a model of the morphologic approach proposed in guidelines for developmental neurotoxicity testing (DNT). Hereto, a limited DNT study [EPA Health Effects Test Guidelines OPPTS 870.6300, 1996a. Developmental Neurotoxicity Study "Public Draft", United States Environmental Protection Agency; Prevention, Pesticides and...article 2005
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de Groot, D.M.G. (author), Hartgring, S. (author), van de Horst, L. (author), Moerkens, M. (author), Otto, M. (author), Bos-Kuijpers, M.H.M. (author), Kaufmann, W.S.H. (author), Lammers, J.H.C.M. (author), O'Callaghan, J.P. (author), Waalkens-Berendsen, I.D.H. (author), Pakkenberg, B. (author), Gundersen, H.G. (author), TNO Kwaliteit van Leven (author)To evaluate the ability of a tiered quantitative morphological approach to reveal developmental neurotoxicity, morphometric parameters were measured in the offspring of rats treated with methylazoxymethanol (MAM) during days 13-15 of pregnancy. Treatment was aimed at inhibiting the proliferation phase of hippocampal neurons while leaving...article 2005
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Brouwer, D.H. (author), de Pater, N.A.J. (author), Zomer, C. (author), Lurvink, M.W.M. (author), van Hemmen, J.J. (author), TNO Kwaliteit van Leven TNO Defensie en Veiligheid (author)The concept of occupational air requirement (OAR), representing the quantity of air required to dilute the vapor concentration in the work environment resulting from 11 product to a concentration below the occupational exposure limit (OEL), was considered to have potential to discriminate between paints that can and cannot be used safely. The...article 2005
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Vreugdenhil, H.J.I. (author), Emmen, H.H. (author), Mulder, P.G.H. (author), Weisglas-Kuperus, N. (author), TNO Voeding (author)PCBs are known for their neurotoxic properties, especially on the developing brain. To increase insight into the neurotoxic effects of PCB exposure, the authors studied the effects of perinatal exposure to environmental levels of these compounds on different neuropsychological domains. In 9-year-old children of the Rotterdam PCB-dioxin cohort,...article 2004
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Degenhardt, C.E.A.M. (author), Pleijsier, K. (author), van der Schans, M.J. (author), Langenberg, J.P. (author), Preston, K.E. (author), Solano, M.I. (author), Maggio, V.L. (author), Barr, J.R. (author), Prins Maurits Laboratorium TNO (author)One of the most appropriate biomarkers for the verification of organophosphorus nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE enzyme by incubation with fluoride ions, after which the resulting organophosphonofluoridate can be...article 2004
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