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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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Mol, M.A.E. (author), van den Berg, R.M. (author), Benschop, H.P. (author), TNO Defensie en Veiligheid (author)While skin is a major target for sulphur mustard (HD), a therapy to limit HD-induced vesication is currently not available. Since it is supposed that apoptotic cell death and proteolytic digestion of extracellular matrix proteins by metalloproteases are initiating factors for blister formation, we have explored whether inhibition of these...article 2009
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Langenberg, J.P. (author), Spruit, W.E.T. (author), Kuijpers, W.C. (author), Mars, R.H. (author), van Helden, H.P.M. (author), van der Schans, G.P. (author), Benschop, H.P. (author), TNO Defensie en Veiligheid (author)ln order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard the toxicokinetics of this agent as well as its major DNA-adducts are being studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in...bookPart 2009
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Diagnosis of exposure to chemical warfare agents: An essential tool to counteract chemical terrorismNoort, D. (author), van der Schans, M.J. (author), Bikker, F.J. (author), Benschop, H.P. (author), TNO Defensie en Veiligheid (author)Methods to analyze chemical warfare agents (CW-agents) and their decomposition products in environmental samples were developed over the last decades. In contrast herewith, procedures for analysis in biological samples have only recently been developed. Retrospective detection of exposure to CW-agents is useful for various applications. It can...bookPart 2009
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- TNO Defensie en Veiligheid (author), Mol, M.A.E. (author), van den Berg, R.M. (author), Benschop, H.P. (author) article 2008
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TNO Defensie en Veiligheid (author), Noort, D. (author), van der Schans, M.J. (author), Benschop, H.P. (author)An overview is presented of the major methods that are presently available for biomonitoring of exposure to chemical warfare agents, i.e., nerve agents and sulfur mustard. These methods can be applied for a variety of purposes such as diagnosis and dosimetry of exposure of casualties, verification of nonadherence to the Chemical Weapon...bookPart 2006
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van der Schans, M.J. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)Traditional multidrug therapy of organophosphorus nerve agent poisoning has several drawbacks such as postexposure incapacitation while optimal timing of administration of the drugs is also crucial. A priori, sequestration of the agent before it can reach its physiological targets would provide optimal protection. Within this context, a plethora...conference paper 2004
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van Helden, H.P.M. (author), Trap, H.C. (author), Kuijpers, W.C. (author), Oostdijk, J.P. (author), Benschop, H.P. (author), Langenberg, J.P. (author), Prins Maurits Laboratorium TNO (author)The purpose of this pilot study was to indicate, for low-level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest-observable-adverse-effect level (LOAEL) of sarin for miosis. This is the concentration × time (C·t) value (t = 5 h) of exposure at which miosis becomes significant. The ratio of pupil and iris...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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Bajgar, J. (author), Ševelová, L. (author), Krejčová, G. (author), Fusek, J. (author), Vachek, J. (author), Kassa, J. (author), Herink, J. (author), de Jong, L.P.A. (author), Benschop, H.P. (author)Soman belongs to the most dangerous nerve agents because of the low effectiveness of the presently available antidotes. Soman acts by inhibiting acetylcholinesterase (AChE) both peripherally and centrally, with a subsequent accumulation of neuromediator acetylcholine and other metabolic changes. From the data published in literature it can be...article 2004
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van Helden, H.P.M. (author), Trap, H.C. (author), Kuijpers, W.C. (author), Oostdijk, J.P. (author), Vanwersch, R.A.P. (author), Phillippens, I.H.C.H.M. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. The purpose of this pilot study was to indicate for sarin: (i) the lowest observable effect level (LOEL), i.e., the C.t-value (t = 5 h) of exposure at which an internal dose (fluoride-regenerated sarin from...conference paper 2004
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Noort, D. (author), Fidder, A. (author), Benschop, H.P. (author), de Jong, L.P.A. (author), Smith, J.R. (author)A procedure for the modified Edman degradation of globin for determination of sulfur mustard adducts to the N-terminal valine residue in human hemoglobin has been developed for use under field laboratory conditions. The minimum detectable exposure level of human blood (in vitro) to sulfur mustard using this procedure is 100nM. The...article 2004
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van der Schans, G.P. (author), Mars-Groenendijk, R. (author), de Jong, L.P.A. (author), Benschop, H.P. (author), Noort, D. (author)A standard operating procedure has been developed for an immunoslotblot assay of sulfur mustard adducts to DNA in human blood and skin for use in a field laboratory. A minimum detectable level of exposure of human blood in vitro (≥ 50nM) sulfur mustard is feasible with the assay. In the case of human skin, a 1 s exposure to saturated sulfur...article 2004
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Prins Maurits Laboratorium TNO (author), van Helden, H.H.P.M. (author), Vanwersch, R.A.P. (author), Kuijpers, W.C. (author), Trap, H.C. (author), Philippens, I.H.C. (author), Benschop, H.P. (author)The main purpose of this pilot study was to estimate the lowest observable adverse effect level (LOAEL) for the electroencephalogram (EEG) upon long-term, low-level exposure of vehicle-pretreated and pyridostigmine-pretreated marmoset monkeys to sarin vapour. This is the C·t value (t = 5 h) of exposure at which the EEG becomes significantly...article 2004
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van Helden, H.P.M. (author), Trap, H.C. (author), Oostdijk, J.P. (author), Kuijpers, W.C. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed...article 2003
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van der Schans, M.J. (author), Lander, B.J. (author), van der Wiel, H. (author), Langenberg, J.P. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatography at blood levels ≥10 pg/ml. The ratio of the...article 2003
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van der Schans, G.P. (author), Noort, D. (author), Mars-Groenendijk, R.H. (author), Fidder, A. (author), Chau, L.F. (author), de Jong, L.P.A. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)As part of a program to develop methods for diagnosis of exposure to chemical warfare agents, we developed immunochemical methods for detection of adducts of sulfur mustard to keratin in human skin. Three partial sequences of keratins containing glutamine or asparagine adducted with a 2-hydroxyethylthioethyl group at the ω-amide function were...article 2002
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Noort, D. (author), Benschop, H.P. (author), Black, R.M. (author), Prins Maurits Laboratorium TNO (author)In this report an overview of the methods currently available for detection of exposure to a number of chemical warfare agents (CWA), i.e., sulfur mustard, lewisite and nerve agents, is presented. Such methods can be applied for various purposes, e.g., diagnosis and dosimetry of exposure of casualties, confirmation of nonexposure, verification...article 2002
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Fidder, A. (author), Hulst, A.G. (author), Noort, D. (author), de Ruiter, R. (author), van der Schans, M.J. (author), Benschop, H.P. (author), Langenberg, J.P. (author), Prins Maurits Laboratorium TNO (author)In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis...article 2002
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- Noort, D. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author) conference paper 2001