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Padro, T. (author), Quax, P.H.A. (author), van den Hoogen, C.M. (author), Roholl, P. (author), Verheijen, J.H. (author), Emeis, J.J. (author), Gaubius Instituut TNO (author)
Plasminogen activator (PA) and PA inhibitor (PAI) antigen, activity, and mRNA were analyzed in the three layers of rat aorta, and the effect of endotoxin on PA and PAI was studied. All PA activity in aorta was identified as tissue-type PA (TPA) activity; no urokinase-type PA was detected. In the tunica adventitia TPA activity, TPA antigen, and...
article 1994
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...
article 2006
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van Raaij, J.A.G.M. (author), Kaptein, E. (author), Visser, T.J. (author), van den Berg, K.J. (author), Medisch Biologisch Laboratorium TNO (author)
Metabolism of thyroid hormones was investigated in WAG/MBL rats that had been exposed to hexachlorobenzene (HCB). Serum thyroxine (T4) levels were lowered by 35.5%, whereas triiodothyronine (T3) levels were not changed. Bile flow, as well as T4 excretion in bile were increased by HCB treatment. Analysis of bile by HPLC revealed a more than 3...
article 1993
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Maas, W.J.M. (author), Leeman, W.R. (author), Groten, J.P. (author), van de Sandt, J.J.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
Precision-cut liver slices are frequently used to study hepatic toxicity and metabolism of xenobiotics in vitro. Successful cryopreservation techniques will enhance an efficient and economic use of scarcely available (human) liver tissue. For primary hepatocytes, slow freezing has been accepted as the best approach towards successful...
article 2000
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Kitayama, K. (author), Nakai, D. (author), Kono, K. (author), van der Hoop, A.G. (author), Kurata, H. (author), de Wit, E.C. (author), Cohen, L.H. (author), Inaba, T. (author), Kohama, T. (author), TNO Preventie en Gezondheid (author)
1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing...
article 2006
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Rijnkels, J.M. (author), Hollanders, V.M.H. (author), Woutersen, R.A. (author), Koeman, J.H. (author), Alink, G.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The potential inhibitory effects of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis were examined in rats fed low- or high-fat diets. Rats were fed low-fat diets (20 energy percent, Diets A and B) or high-fat diets (40 energy percent, Diets C and D), supplemented with a...
article 1998
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Anderson, D. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO BIBRA (author)
Butadiene (BD) and its 2-methyl analogue, isoprene, have been extensively studied in animals and BD in population studies. Both chemicals are metabolised by liver cytochrome P450 dependent monogenases to monoepoxide and diepoxide intermediates. The diepoxide intermediates of both compounds were mutagenic in Salmonella typhimurium. However,...
article 2001
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Lina, B.A.R. (author), Bos-Kuijpers, M.H.M. (author), Til, H.P. (author), Bär, A. (author)
The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two satellite groups of 20 males each were attached for...
article 1996
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Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)
As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...
article 2007
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Izeboud, C.A. (author), Hoebe, K.H.N. (author), Grootendorst, A.F. (author), Nijmeijer, S.M. (author), van Miert, A.S. (author), Witkamp, R.F. (author), Rodenburg, R.J.T. (author), TNO Voeding (author)
Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The β2-selective AR agonist clenbuterol was...
article 2004
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Kuper, C.F. (author), van Zijverden, M. (author), Klaassen, C. (author), Tegelenbosch-Schouten, M. (author), Wolterbeek, A.P.M. (author), TNO Kwaliteit van Leven (author)
The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats...
article 2007
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Cassee, F.R. (author), Muijser, H. (author), Duistermaat, E. (author), Freijer, J.J. (author), Geerse, E.K.B. (author), Marijnissen, J.C.M. (author), Arts, J.H.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)
The relative importance of the three particulate matter (PM) size fractions in ambient air, i.e. coarse (2.5-10 μm), fine (0.1-2.5 μm) and ultrafine (< 0.1 μm) fractions, on the induction of adverse health effects is still unknown. Moreover, there is no straightforward relationship between ambient concentration levels, exposure (external dose)...
article 2002
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Padró, T. (author), van den Hoogen, C.M. (author), Emeis, J.J. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)
The aim of the present study was to investigate whether hypothyroidism would affect the components of the rat plasma fibrinolytic system. Hypothyroidism was induced by feeding rats a thiouracil-containing diet for 2 weeks. During this period, half of the animals received subcutaneous injections of L-thyroxine (20 μg/kg daily) to restore thyroid...
article 1993
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Zwart, A. (author), Arts, J.H.E. (author), ten Berge, W.F. (author), Appelman, L.M. (author)
A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a concentration-time-mortality relationship, enabling calculation of LC50...
article 1992
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Lina, B.A.R. (author), Kuijpers, M.H.M. (author), TNO Voeding (author)
The effects of diet-induced acid-base disturbances were examined in 4-week, 13-week and 18-month toxicity studies, and in a 30-month carcinogenicity study. Rats were fed a natural ingredient diet (controls), supplemented with 2% or 4% KHCO3 (base-forming diets), or with 1% or 2.1% NH4Cl (acid-forming diets). Additional controls were fed 3% KCl ...
article 2004
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Wolterbeek, A.P.M. (author), Roberts, A. (author), Korte, H. (author), Unkila, M. (author), Waalkens-Berendsen, D.H. (author), TNO Voeding (author)
Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex (HMRlignan; potassium acetate level...
article 2004
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Visser, C.J.T. (author), van Garderen-Hoetmer, A. (author), Klijn, J.G.M. (author), Foekens, J.A. (author), Woutersen, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)
In a previous short-term study (4 months) we found that Sandostatin, when administered prophylactically, inhibited growth of putative pre-neoplastic ductular lesions induced in hamster pancreas by N-nitrosobis(2-oxopropyl)amine (BOP), but not of acinar lesions induced in rat pancreas by azaserine. The present long-term (12 months) study was...
article 1996
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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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Appelman, L.M. (author), Hendriksen, C.F.M. (author), Feron, V.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The subacute inhalation toxicity of ??-ethylacrolein was examined in rats by repeated exposure of 4 groups of 10 males and 10 females each to ??-ethylacrolein vapour at concentrations of 0, 2.0, 9.8 or 48.4 ppm, respectively, (6 h/day, 5 days/week) for a period of 13 weeks. The effects at 48.4 ppm were found to include growth retardation, focal...
article 1981
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Lina, B.A.R. (author), Bär, A. (author), TNO Voeding (author)
The toxicity of α-cyclodextrin (α-CD), a cyclic polymer of six α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week study, the test substance was administered to...
article 2004
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