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Regulatory acceptance and use of the extended one generation reproductive toxicity study within Europe

Schiffelers, M.J.W.A. (author), Blaauboer, B.J. (author), Bakker, W.E. (author), Hendriksen, C.F.M. (author), Krul, C. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

The two-generation study (OECD TG 416) is the standard requirement within REACH to test reproductive toxicity effects of chemicals with production volumes >100. tonnes. This test is criticized in terms of scientific relevance and animal welfare. The Extended One Generation Reproductive Toxicity Study (EOGRTS), incorporated into the OECD test...

article 2015

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Effects of a diet high in fish oil (MaxEPA) on the formation of micronucleated erythrocytes in blood and on the number of atypical acinar cell foci induced in rat pancreas by Azaserine

Appel, M.J. (author), Woutersen, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci (AACF) as a measure for the actual number of...

article 2004

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Particle size-dependent total mass deposition in lungs determines inhalation toxicity of cadmium chloride aerosols in rats: Application of a multiple path dosimetry model

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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Monitoring of pesticide applicators for potential dermal exposure to malathion and biomarkers in urine

Tuomainen, A. (author), Kangas, J.A. (author), Meuling, W.J.A. (author), Glass, R.C. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Malathion was applied to roses in three Finnish greenhouses by hand held lance sprayers. The potential dermal exposure of applicators to this insecticide was measured. Total urine production of each applicator was also collected up to 24 h post application. In the urine samples the specific metabolite of malathion, malathion monocarboxylic acid ...

article 2002

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Evaluation of the sensory irritation test (alarie test) for the assessment of respiratory tract irritation

Bos, P.M.J. (author), Busschers, M. (author), Arts, J.H.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Within the framework of risk assessment of existing substances in the EC the irritating properties on the respiratory tract should be considered. Since no standardized test is available it was studied whether the Alarie test could be used for this purpose, as proposed by the Technical Guidance Document for new and existing substances. The...

article 2002

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Environmental risk assessment of phosphonates, used in domestic laundry and cleaning agents in the Netherlands

Jaworska, J. (author), van Genderen-Takken, H. (author), Hanstveit, A. (author), van de Plassche, E. (author), Feijtel, T. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

In the long-term cooperative project Voluntary Plan of Action (1990) between the Dutch Soap and Detergent Association (NVZ) and the Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) environmental risk assessments of several main components of laundry cleaning formulations were completed. As a part of that project the...

article 2002

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Isomaltulose (Palatinose R): A review of biological and toxicological studies

Lina, B.A.R. (author), Jonker, D. (author), Kozianowski, G. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Isomaltulose is a natural occurring disaccharide composed of α-1,6-linked glucose and fructose. Commercial isomaltulose is produced from sucrose by enzymatic rearrangement and has been used as a sugar in Japan since 1985. It is particularly suitable as a non-cariogenic sucrose replacement and is favorable in products for diabetics and...

article 2002

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Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

Rennen, M.A.J. (author), Nordheim, K. (author), Houben, G.F. (author), de Heer, C. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in route-to-route extrapolation is the occurrence...

article 2002

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Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - methyl eugenol and estragole

Smith, R.L. (author), Adams, T.B. (author), Doull, J. (author), Feron, V.J. (author), Goodman, J.I. (author), Marnett, L.J. (author), Portoghese, P.S. (author), Waddell, W.J. (author), Wagner, B.M. (author), Rogers, A.E. (author), Caldwell, J. (author), Sipes, I.G. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data...

article 2002

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Trehalose: A review of properties, history of use and human tolerance, and results of multiple safety studies

Richards, A.B. (author), Krakowka, S. (author), Dexter, L.B. (author), Schmid, H. (author), Wolterbeek, A.P.M. (author), Waalkens-Berendsen, D.H. (author), Shigoyuki, A. (author), Kurimoto, M. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

This paper contains a review of the history, natural occurrence, human consumption, metabolism, manufacture, and the results of eight standardized animal safety studies using trehalose. Trehalose (α,α-trehalose) is a naturally occurring sugar containing two D-glucose units in an α,α-1,1 linkage. Trehalose functions in many organisms as an energy...

article 2002

document

The contribution of epidemiology

van den Brandt, P. (author), Voorrips, L. (author), Hertz-Picciotto, I. (author), Shuker, D. (author), Boeing, H. (author), Speijers, G. (author), Guittard, C. (author), Kleiner, J. (author), Knowles, M. (author), Wolk, A. (author), Goldbohm, A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Epidemiologic studies directly contribute data on risk (or benefit) in humans as the investigated species, and in the full food intake range normally encountered by humans. This paper starts with introducing the epidemiologic approach, followed by a discussion of perceived differences between toxicological and epidemiologic risk assessment....

article 2002

document

Post-application exposure of workers to pesticides in agriculture

Instituut CIVO-Toxicologie en Voeding TNO (author), van Hemmen, J.J. (author), Chester, G. (author), Hamey, P. (author), Kangas, J. (author), Kirknel, E. (author), Maasfeld, W. (author), Perkins, J. (author), Philips, J. (author), Schulze-Rosario, C. (author)

report 2002

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The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids

Rietjens, I.M.C.M. (author), Boersma, M.G. (author), de Haan, L. (author), Spenkelink, B. (author), Awad, H.M. (author), Cnubben, N.H.P. (author), van Zanden, J.J. (author), van der Woude, H. (author), Alink, G.M. (author), Koeman, J.H. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Natural antioxidants like vitamin C, vitamin E, carotenoids, and polyphenols like flavonoids, are at present generally considered to be beneficial components from fruit and vegetables. The anti-oxidative properties of these compounds are often claimed to be responsible for various beneficial health effects of these food ingredients. Together...

article 2002

document

The use of in vitro metabolic parameters and physiologically based pharmacokinetic (PBPK) modeling to explore the risk assessment of trichloroethylene

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

document

Nuclear factor-kB activation is higher in peripheral blood mononuclear cells of male smokers

van den Berg, R. (author), Haenen, G.R.M.M. (author), van den Berg, H. (author), Bast, A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Nuclear factor-κB (NF-κB) is an oxidative stress sensitive transcription factor involved in the regulation of inflammatory genes. Activation of NF-κB results into increased expression of inflammatory genes such as for interleukins, endothelial cell leukocyte adhesion molecules and inducible NO synthase. Our study, with six smokers and 10 non...

article 2001

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Disposition, accumulation and toxicity of iron fed as iron (II) sulfate or as sodium iron EDTA in rats

Appel, M.J. (author), Kuper, C.F. (author), Woutersen, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

A study was performed to provide data on the disposition, accumulation and toxicity of sodium iron EDTA in comparison with iron (II) sulfate in rats on administration via the diet for 31 and 61 days. Clinical signs, body weights, food consumption, food conversion efficiency, hematology, clinical chemistry and pathology of selected organs were...

article 2001

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Determination of protein allergenicity: Studies in rats

Penninks, A.H. (author), Knippels, L.M.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

For the safety evaluation of genetically engineered crops the potential allergenicity of the newly introduced protein(s) has become an important issue. There is, however, no universal and reliable test system for the evaluation of the allergenic potency of food products. The best known allergy assessment proposal is the careful stepwise process...

article 2001

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Total regional and global number of synapses in the human brain neocortex

Tang, Y. (author), Nyengaard, J.R. (author), de Groot, D.M.G. (author), Jorgen, H. (author), Gundersen, G. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region of neocortex was performed. The total volume...

article 2001

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Residential exposure should be considered in appropriate terms: Summary of discussions

van der Jagt, K.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Chemicals/CAS: Pesticides

article 2001

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Niacin, poly(ADP-ribose) polymerase-1 and genomic stability

Hageman, G.J. (author), Stierum, R.H. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Nicotinic acid (NA) and nicotinamide (NAM), commonly called niacin, are the dietary precursors for NAD+ (nicotinamide adenine dinucleotide), which is required for DNA synthesis, as well as for the activity of the enzyme poly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30) for which NAD+ is the sole substrate. The enzyme PARP-1 is highly activated...

article 2001