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Hempenius, R.A. (author), Lina, B.A.R. (author), Haggitt, R.C. (author)Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,000 ppm and 75,000 ppm. An additional high-dose...article 2000
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Jacobs, J.J.L. (author), Lehé, C. (author), Cammans, K.D.A. (author), Das, P.K. (author), Elliott, G.R. (author)We describe a new alternative method for screening for skin irritants by using fresh intact porcine skin biopsies. Test chemicals were applied to the epidermis of the biopsies, which were then incubated for different times in tissue culture medium at 37°C and with 5% carbon dioxide. A decrease in epidermal keratinocyte RNA staining, visualised...article 2000
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Walton, K. (author), Walker, R. (author), van de Sandt, J.J.M. (author), Castell, J.V. (author), Knapp, A.G.A.A. (author), Kozianowski, G. (author), Roberfroid, M. (author), Schilter, B. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)The acceptable daily intake (ADI) for food additives is commonly derived from the NOAEL (no-observed-adverse-effect level) in long-term animal in vivo studies. To derive an ADI a safety or uncertainty factor (commonly 100) is applied to the NOAEL in the most sensitive test species. The 100-fold safety factor is considered to be the product of...article 1999
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Woutersen, R.A. (author), Wolterbeek, A.P.M. (author), Appel, M.J. (author), van den Berg, H. (author), Goldbohm, R.A. (author), Feron, V.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The safety of β-carotene was reassessed by evaluating the relevant literature on the beneficial and adverse effects of β-carotene on cancer and, in particular, by evaluating the results of toxicity studies. β- Carotene appeared neither genotoxic nor reprotoxic or teratogenic, and no signs of organ toxicity have been found in subacute, subchronic...article 1999
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Bär, A. (author), Lina, B.A.R. (author), de Groot, D.M.G. (author), de Bie, B. (author), Appel, M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)D-Tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any...article 1999
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Vermeire, T. (author), Stevenson, H. (author), Pieters, M.N. (author), Rennen, M. (author), Slob, W. (author), Hakkert, B.C. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factors to be identified, the range of values...article 1999
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Gerritsen, A. (author), van der Hoeven, N. (author), Pielaat, A. (author)Differences in sensitivity toward toxicants between young and adult individuals in a population are assumed to be primarily associated with their difference in body size. This assumption plays a key role in the modeling of effects of variable concentrations of toxicants on nonhomogeneous populations. The hazardbased no-effect-concentrations ...article 1998
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Bowmer, C.T. (author), Hooftman, R.N. (author), Hanstveit, A.O. (author), Venderbosch, P.W.M. (author), van der Hoeven, N. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)The ecotoxicity of lactic acid, its alkyl esters and selected metal salts was studied experimentally with the micro alga Selenastrum capricornutum, the crustacean Daphnia magna and the fish species Brachydanio rerio and Pimephales promelas. In addition, the biodegradation of lactate esters was also studied. The aim of the study was to provide...article 1998
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Noort, D. (author), Hulst, A.G. (author), Platenburg, D.H.J.M. (author), Polhuijs, M. (author), Benschop, H.P. (author), Prins Maurits Laboratorium TNO (author)A convenient and rapid micro-anion exchange liquid chromatography (LC) tandem electrospray mass spectrometry (MS) procedure was developed for quantitative analysis in serum of O-isopropyl methylphosphonic acid (IMPA), the hydrolysis product of the nerve agent sarin. The mass spectrometric procedure involves negative or positive ion electrospray...article 1998
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de Nijs, M. (author), van Egmond, H.P. (author), Nauta, M. (author), Rombouts, F.M. (author), Notermans, S.H.W. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Fumonisin B1 is currently regarded as the most significant mycotoxin produced by Fusarium spp. It has carcinogenic properties and may play a role in the etiology of human esophageal cancer. The human population is exposed to fumonisin B1 primarily by intake of fumonisin B1-contaminated maize. Maize consumed in the Netherlands is imported from...article 1998
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Stouten, H. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)As part of a health-hazard survey on the health risk of hospital cleaning workers from exposure to Lyorthol, a hazard assessment of o-phenylphenol (and its sodium salt), one of the constituents of Lyorthol, has been prepared, In this paper, the physical and chemical characteristics, kinetics and effects of o-phenylphenol and its sodium salt are...article 1998
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voedin (author), Groten, J.P. (author), Tajima, O. (author), Feron, V.J. (author), Schoen, E.D. (author)For the accurate analysis of possible interactive effects of chemicals in a defined mixture, statistical designs are necessary to develop clear and manageable experiments. For instance, factorial designs have been successfully used to detect two-factor interactions. Particularly useful for this purpose are fractionated factorial designs,...article 1998
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Chamberlain, M. (author), Gad, S.C. (author), Gautheron, P. (author), Prinsen, M.K. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)The brief of the Organotypic Models Working Group was to review data submitted to the Interagency Regulatory Alternatives Group on the use of isolated eyes and components of the eye used to predict eye irritation potential. Data submissions were received on four test systems: the isolated rabbit eye (one submission), the isolated chicken eye ...article 1997
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Gruys, E. (author), Tooten, P.C.J. (author), Kuijpers, M.H.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Amyloid deposits represent frequent histological findings in SPF strains of mice mainly used for toxicological studies. Usually, these are deposits of reactive amyloid (AA-amyloid) derived from the acute phase protein serum amyloid A (SAA). The SAA is an apoprotein of high density lipoprotein (apoSAA). Senescence-accelerated amyloid (ASsam)...article 1996
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Prinsen, M.K. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)The enucleated eye test with chicken eyes (CEET) obtained from an abattoir proved to be a valuable and practical alternative for the 'traditional' enucleated eye test with eyes of laboratory rabbits. Since 1992, the CEET has been incorporated in standard contract toxicity testing at the Toxicology Division of the TNO Nutrition and Food Research...article 1996
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Kulig, B. (author), Alleva, E. (author), Bignami, G. (author), Cohn, J. (author), Cory-Slechta, D. (author), Landa, V. (author), O'donoghue, J. (author), Peakall, D. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Chemicals/CAS: Neurotoxinsarticle 1996
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Coenen, T.M.M. (author), Schoenmakers, A.C.M. (author), Verhagen, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Barlican, a β-glucanase enzyme obtained from Trichoderma reesei, was produced by a fermentation process and subjected to a series of toxicological tests to document its safety for use as a feed additive. The enzyme product was examined for general oral toxicity, inhalation toxicity, irritation to eye and skin, skin sensitization and mutagenic...article 1995
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Feron, V.J. (author), Groten, J.P. (author), Jonker, D. (author), Cassee, F.R. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)A major challenge for the toxicologist involved in safety evaluation of chemical mixtures is to test the hypothesis that as a rule exposure to mixtures of chemicals at (low) non-toxic doses of the individual chemicals is of no health concern. A series of repeated dose studies in rats with defined mixtures of chemicals with the same or different...article 1995
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van de Sandt, J.J.M. (author), Maas, W.J.M. (author), Doornink, P.C. (author), Rutten, A.A.J.J.L. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)In vitro techniques make a major contribution to the development of alternatives to the in vivo 'Draize' skin irritation test, and the development of sensitive and generally applicable in vitro endpoints of cutaneous toxicity is an area of intensive research. To investigate in vitro characteristics of cutaneous irritation, skin explants of...article 1995
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Emeis, J.E. (author), Hoekzema, R. (author), de Vos, A.F. (author), TNO Preventie en Gezondheid (author)In experimental animals and humans, intravenous (IV) injection of endotoxin induces large increases in circulating plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of blood fibrinolysis. A similar increase is seen after the injection of interleukin-1 (IL-1) or of tumor necrosis factor-α (TNF-α), suggesting that these cytokines...article 1995