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van den Dries, M.A. (author), Lamballais, S. (author), El Marroun, H. (author), Pronk, A. (author), Spaan, S. (author), Ferguson, K.K. (author), Longnecker, M.P. (author), Tiemeier, H. (author), Guxens, M. (author)Background: Prenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine...article 2020
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van den Dries, M.A. (author), Guxens, M. (author), Pronk, A. (author), Spaan, S. (author), El Marroun, H. (author), Jusko, T.A. (author), Longnecker, M.P. (author), Ferguson, K.K. (author), Tiemeier, H. (author)Background: Prenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder ...article 2019
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Joosen, M.J.A. (author), van den Berg, R.M. (author), de Jong, A.L. (author), van der Schans, M.J. (author), Noort, D. (author), Langenberg, J.P. (author)The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first...article 2017
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Koster, S. (author), Leeman, W.R. (author), Verheij, E.R. (author), Dutman, A.E. (author), van Stee, L.L.P. (author), Munch Nielsen, L. (author), Ronsmans, S. (author), Noteborn, H. (author), Krul, L. (author)A main challenge in food safety research is to demonstrate that processing of foodstuffs does not lead to the formation of substances for which the safety upon consumption might be questioned. This is especially so since food is a complex matrix in which the analytical detection of substances, and consequent risk assessment thereof, is difficult...article 2015
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Spaan, S. (author), Pronk, A. (author), Koch, H.M. (author), Jusko, T.A. (author), Jaddoe, V.M.W. (author), Shaw, P.A. (author), Tiemeier, H.M. (author), Hofman, A. (author), Pierik, F.H. (author)The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the...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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Houtzager, M.M.G. (author), Havermans, J.B.G.A. (author), Bos, J.G.H. (author), Makarem Akhlaghi, H. (author), Hijman, W.C. (author), Renesse van Duivenbode, J.A.D. (author), Jedynska, A.D. (author)In our simulation experiments, using e.g., a dedicated emission chamber, the emission of organophosphates as tricresyl phosphate (TCP) was studied using turbine oil. Experiments were carried out at 250°C and 370°C. Subsequently field studies were carried out to detect the presence of TCPs in the cockpit during normal operating conditions of...conference paper 2014
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Koster, S. (author), Rennen, M. (author), Leeman, W. (author), Houben, G. (author), Muilwijk, B. (author), van Acker, F. (author), Krul, L. (author)One of the main challenges in food contact materials research is to prove that the presence of non-intentionally added substances (NIAS) is not a safety issue. Migration extracts may contain many unknown substances present at low concentrations. It is difficult and time-consuming to identify all these potential NIAS and concurrently to assess...article 2014
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van der Schans, M.J. (author), Hulst, A.G. (author), van der Riet-Van Oeveren, D. (author), Noort, D. (author), Benschop, H.P. (author), Dishovsky, C. (author)Organophosphate (OP) pesticides are neurotoxic compounds that are widely used in agriculture. Classical methods for monitoring OP exposure comprise the measurement of intact OP, its metabolites or cholinesterase activity. Newly developed methods focus on the analysis of the OP adduct bound to proteins such as butyrylcholinesterase (BuChE) and...article 2013
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Joosen, M.J.A. (author), Smit, A.B. (author), van Helden, H.P.M. (author)Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical...article 2011
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Joosen, M.J.A. (author), van der Schans, M.J. (author), van Helden, H.P.M. (author), TNO Defensie en Veiligheid (author)The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the...article 2010
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van der Meer, J.A. (author), Trap, H.C. (author), Noort, D. (author), van der Schans, M.J. (author), TNO Defensie en Veiligheid (author)Recently, several methods have been developed to verify exposure to nerve agents. Most of these methods, such as the fluoride reactivation technique and the analysis of inhibited phosphonylated butyrylcholinesterase (BuChE), are based on mass spectrometry. The high specificity of the mass spectrometer might also imply a disadvantage, because the...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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Ye, X. (author), Pierik, F.H. (author), Angerer, J. (author), Meltzer, H.M. (author), Jaddoe, V.W.V. (author), Tiemeier, H. (author), Hoppin, J.A. (author), Longnecker, M.P. (author), TNO Bouw en Ondergrond (author)Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples...article 2009
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TNO Defensie en Veiligheid (author), Tuin, A.W. (author), Mol, M.A.E. (author), van den Berg, R.M. (author), Fidder, A. (author), van der Marel, G.A. (author), Overkleeft, H.S. (author), Noort, D. (author)Elucidation of noncholinesterase protein targets of organophosphates, and nerve agents in particular, may reveal additional mechanisms for their high toxicity as well as clues for novel therapeutic approaches toward intoxications with these agents. Within this framework, we here describe the synthesis of the activity-based probe 3, which...article 2009
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Noort, D. (author), Fidder, A. (author), van der Schans, M.J. (author), Hulst, A.G. (author), TNO Defensie en Veiligheid (author)We present a generic mass spectrometric method to verify exposure to organophosphates, based on the chemical conversion of the phosphylated peptides obtained after pepsin digestion of human butyrylcholinesterase (HuBuChE) to a common precursor peptide. After exposure of plasma to various organophosphates (nerve agents, pesticides), HuBuChE was...article 2006
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Smulders, C.J.G.M. (author), Bueters, T.J.H. (author), Vailati, S. (author), van Kleef, R.G.D.M. (author), Vijvergberg, H.P.M. (author)Chronic and acute exposure to organophosphate (OP) pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. It is suggested that other brain proteins are involved. Effects of commonly used organophosphate pesticides on rat neuronal α4β2 nicotinic...article 2004
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Prins Maurits Laboratorium TNO (author), van der Schans, M.J. (author), Polhuijs, M. (author), van Dijk, C. (author), Degenhardt, C.E.A.M. (author), Pleijsier, K. (author), Langenberg, J.P. (author), Benschop, H.P. (author)The utility was explored of a new approach to detect retrospectively exposure to nerve agents by means of conversion of the inhibitor moiety bound to the active site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate which is subsequently analyzed by means of gas chromatography (GC). This quantifies ≥0.01% inhibition of...article 2004
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Mol, H.G.J. (author), van Dam, R.C.J. (author), Steijger, O.M. (author), TNO Voeding (author)A method based on liquid chromatography (LC)-mass spectrometry (MS)/MS was developed for sensitive determination of a number of less gas chromatography (GC)-amenable organophosphorus pesticides (OPs; acephate, methamidophos, monocrotophos, omethoate, oxydemeton-methyl and vamidothion) in cabbage and grapes. For extraction, several solvents were...article 2003
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Bueters, T.J.H. (author), Groen, B. (author), Danhof, M. (author), IJzerman, A.P. (author), van Helden, H.P.M. (author), Prins Maurits Laboratorium TNO (author)The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. The OPs studied were tabun (O-ethyl-N-dimethylphosphoramidocyanidate), sarin (isopropylmethylphosphonofluoridate), VX (O...article 2002
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