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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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Hulst, A.G. (author), Verstappen, D.R.W. (author), van der Riet-van Oeveren, D. (author), Vermeulen, N.P.E. (author), Noort, D. (author)In the current paper we show that exposure of human callus to isocyanates leads to covalent modifications within keratin proteins. Mass spectrometric analyses of pronase digests of keratin isolated from exposed callus show that both mono- and di-adducts (for di-isocyanates) are predominantly formed on the ε-amino group of lysine. In addition,...article 2015
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Verstappen, D.R.W. (author), Hulst, A.G. (author), Fidder, A. (author), Vermeulen, N.P.E. (author), Noort, D. (author)Methods to unequivocally assess and quantify exposure to organophosphate anti-cholinesterase agents are highly valuable, either from a biomonitoring or a forensic perspective. Since for both OP pesticides and various nerve agents the skin is a predominant route of entry, we hypothesized that proteins in the skin might represent an ideal source...article 2012
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Damsten, M.C. (author), Commandeur, J.N.M. (author), Fidder, A. (author), Hulst, A.G. (author), Touw, D. (author), Noort, D. (author), Vermeulen, N.P.E. (author), TNO Defensie en Veiligheid (author)Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of...article 2007
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Hissink, E.M. (author), Bogaards, J.J.P. (author), Freidig, A.P. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)A physiologically based pharmacokinetic (PBPK) model has been developed for trichloroethylene (1,1,2-trichloroethene, TRI) for rat and humans, based on in vitro metabolic parameters. These were obtained using individual cytochrome P450 and glutathione S-transferase enzymes. The main enzymes involved both for rats and humans are CYP2E1 and the μ-...article 2002
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Vermeulen, N.P.E. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Interindividual variability in the disposition and effects of xenobiotics in humans and related inter-species differences should play a major role in human risk assessment. In particular for low-dose exposures to potentially carcinogenic compounds, novel tools and concepts are necessary to assess risks of chemical exposure, preferably based on...article 2001
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Hissink, A.M. (author), Wormhoudt, L.W. (author), Sherratt, P.J. (author), Hayes, J.D. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new data were used for the human class ΘGST T1-1....article 2000
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- Wormhoudt, L.W. (author), Hissink, A.M. (author), Commandeur, J.N.M. (author), van Bladeren, P.J. (author), Vermeulen, N.P.E. (author), Centraal Instituut voor Voedingsonderzoek TNO (author) article 1998
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Bessems, J.G.M. (author), de Groot, M.J. (author), Baede, E.J. (author), te Koppele, J.M. (author), Vermeulen, N.P.E. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)1. The formation of free radicals during enzyme catalysed oxidation of eight 3,5-disubstituted analogues of paracetamol (PAR) has been studied. A simple peroxidase system as well as cytochrome P450-containing systems were used. Radicals were detected by electron spin resonance (ESR) on incubation of PAR and 3,5-diCH3-, 3,5-diC2H5-, 3,5-ditC4H9-,...article 1998
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- Wormhoudt, L.W. (author), Commandeur, J.N.M. (author), Ploemen, J.H.T.M. (author), Abdoelgafoer, R.S. (author), Makansi, A. (author), van Bladeren, P.J. (author), Vermeulen, N.P.E. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author) article 1997
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TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author), Ploemen, J.P.H.T.M. (author), Wormhoudt, L.W. (author), Haenen, G.R.M.M. (author), Oudshoorn, M.J. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), de Waziers, I. (author), Beaune, P.H. (author), Watabe, T. (author), van Bladeren, P.J. (author)Ethylene dibromide (1,2-dibromoethane, EDB) is metabolized by two routes: a conjugative route catalyzed by glutathione S-transferases (GST) and an oxidative route catalyzed by cytochrome P450 (P450). The GST route is associated with carcinogenicity. An approach is presented to use human purified GST and P450 enzymes to explore the importance of...article 1997
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Bessems, J.G.M. (author), te Koppele, J.M. (author), van Dijk, P.A. (author), van Stee, L.L.P. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), Leiden/Amsterdam Ctr. for Drug Res., Division of Molecular Toxicology, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, Netherlands Dept. Vasc. Connective Tissue Res TNO Preventie en Gezondheid (author)1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -C(H)3, -C2H5, -iC3H7) have been determined with β-naphthoflavone (βNF)-induced rat liver microsomes and produced reverse type I spectral changes. K(s,app) varied from 0.14 mM for 3,5-diiC3H7-paracetamol to 2.8...article 1996
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van der Aar, E.M. (author), Buikema, D. (author), Commandeur, J.N.M. (author), te Koppele, J.M. (author), van Ommen, B. (author), van Bladeren, P.J. (author), Vermeulen, N.P.E. (author), Leiden/Amsterdam Ctr. for Drug Res., Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, Netherlands TNO Preventie en Gezondheid TNO Voeding (author)1. Four different rat glutathione S-transferase (GST) isoenzymes, belonging to three different classes, were examined for their GSH conjugating capacity towards 11 2-substituted 1-chloro-4-nitrobenzene derivatives. Significant differences were found in their enzyme kinetic parameters K(m), k(cat) and k(cat)/K(m). 2. Substrates with bulky...article 1996
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Wormhoudt, L.W. (author), Ploemen, J.H.T.M. (author), de Waziers, I. (author), Commandeur, J.N.M. (author), Beaune, P.H. (author), van Bladeren, P.J. (author), Vermeulen, N.P.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)1,2-Dibromoethane (1,2-DBE) is mainly used as an additive in leaded gasoline and as a soil fumigant and it is a suspected carcinogen in humans. In this study, the oxidative bioactivation of 1,2-DBE to 2-bromoacetaldehyde (2-BA) was studied using heterologously expressed human cytochrome P450 (P450) isoenzymes and human liver microsomes. Out of...article 1996
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Ploemen, J.-P.H.T.M. (author), van Iersel, M.L.P.S. (author), Wormhoudt, L.W. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), van Bladeren, P.J. (author)The drug disulfiram (DSF, Antabuse®) has been used in the therapy of alcohol abuse. It is a potent inhibitor of aldehyde dehydrogenase. Its reduced form, diethyldithiocarbamate (DDTC), and further metabolites show similar activities. DSF and DDTC have also been widely used to inhibit mixed-function oxidases. In this study, the reversible...article 1996
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- Goeptar, A.R. (author), Commandeur, J.N.M. (author), van Ommen, B. (author), van Bladeren, P.J. (author), Vermeulen, N.P.E. (author), Centraal Instituut voor Voedingsonderzoek TNO (author) article 1995
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Ploemen, J.H.T.M. (author), Wormhoudt, L.W. (author), van Ommen, B. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)In this study a polymorphism in the conjugating activity of human erythrocyte cytosol towards the dihaloethane, ethylene dibromide (EDB; 1,2-dibromoethane) was found. Two out of 12 human erythrocyte cytosols did not catalyze the formation of glutathione (GSH) conjugates of [1,2-14C]EDB. Ten cytosols formed the S,S'-ethylenebis(GSH) conjugate at...article 1995
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Koymans, L.M.H. (author), Menge, W.M.P.B. (author), Donné-Op Den Kelder, G.M. (author), te Koppele, J.M. (author), Vermeulen, N.P.E. (author), van Lenthe, J.H. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)The oxidative metabolism of 4-chloroacetanilide (4-ClAA, 1) by cytochrome P450 has been studied theoretically using ab-initio energy and spin-distribution calculations. A mechanism of oxidation for 4-ClAA is proposed which is in accordance with recent views on the mechanism of metabolic oxidation of substrates by cytochrome P450. An initial one...article 1993
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Medisch Biologisch Laboratorium TNO (author), Brouwer, E.J. (author), Brouwer, D.H. (author), Bruynzeel, D.P. (author), Emmen, H.H. (author), van Hemmen, J.J. (author), Hooisma, J. (author), Jonkman, E.J. (author), Ruijten, M.W.M.M. (author), Salle, H.J.A. (author), Sjardin, W. (author), Verberk, M.M. (author), Vermeulen, N.P.E. (author), de Weerd, A.W. (author), van Welie, R.T.H. (author), Zielhuis, R.L. (author), de Wolff, F.A. (author)In the Dutch flower bulb culture a large number of pesticides is used for different applications : weed control, crop protection, disinfection of barns (stock protection) and soil, and bulb disinfection. A study was therefore carried out in order to investigate : (1) the type and extent of exposure to pesticides in the flower bulb culture, and ...book 1992
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Brouwer, D.H. (author), Brouwer, E.J. (author), de Vreede, J.A.F. (author), van Welie, R.T.H. (author), Vermeulen, N.P.E. (author), van Hemmen, J.J. (author), Medisch Biologisch Laboratorium TNO (author)Respiratory occupational exposure to the Z- and E-isomers of 1,3-dichloropropene (DCP) of twelve commercial applicators was assessed. The time-weighted average (TWA) concentrations of DCP ranged from 1.9 to 18.9 mg/m3. On 30% of the observed working days the Dutch occupational exposure limit of 5 mg/m3 was exceeded. Short-term exposure levels...article 1991