document

Organotypic models for the assessment/prediction of ocular irritation

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

document

Effect of coexposure to methyl ethyl ketone (MEK) on n-hexane toxicokinetics in human volunteers

Instituut CIVO-Toxicologie en Voeding TNO (author), van Engelen, J.G.M. (author), de Rebel-Haan, W. (author), Opdam, J.J.G. (author), Mulder, G.J. (author)

In order to study the effects of methyl ethyl ketone (MEK) on the toxicokinetics of n-hexane and, in particular, the formation of 2,5-hexanedione from n-hexane in humans, volunteers were exposed to n-hexane (approx. 60 ppm, 2.4 μM in the inhaled air) with or without simultaneous inhalatory coexposure to MEK for 15.5 min. The concentration-time...

article 1997

document

Preventive effectiveness of pre-employment medical assessments

de Kort, W. (author), van Dijk, F. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Objectives and methods - Health gain, prevention of health loss, and avoidance of financial risk all seem to be driving forces for the use of pre-employment medical assessment. An attempt is made to measure the effect of implementing the pre-employment medical assessment on these end points. The anticipated maximum preventive effect (preventive...

article 1997

document

Calcium excretion, apparent calcium absorption and calcium balance in young and elderly subjects: Influence of protein intake

Instituut CIVO-Toxicologie en Voeding TNO (author), Pannemans, D.L.E. (author), Schaafsma, G. (author), Westerterp, K.R. (author)

The present study was conducted to investigate the effect of dietary protein on urinary Ca excretion, apparent Ca absorption and Ca balance in young and elderly subjects. Young adults (n 29) and elderly persons (n 26) consumed diets containing 12% (diet A) and 21% (diet B) of total energy as protein for 3 weeks according to a randomized...

article 1997

document

Effects of sandostatin, alone and in combination with surgical castration, on pancreatic carcinigenesis in rats and hamsters

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

document

Biomonitoring human exposure to environmental carcinogenic chemicals

Farmer, P.B. (author), Sepai, O. (author), Lawrence, R. (author), Autrup, H. (author), Nielsen, P.S. (author), Baan, R.A. (author), van Delft, J.H.M. (author), Steenwinkel, M.J.S.T. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of secondary biological effects (mutation and cytogenetic damage)....

article 1996

document

Toxicity of formaldehyde and acrolein mixtures: In vitro studies using nasal epithelial cells

Cassee, F.R. (author), Stenhuis, W.S. (author), Groten, J.P. (author), Feron, V.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehyde dehydrogenases were inhibited by disulfiram...

article 1996

document

Cell proliferation and DNA adducts in hamster tracheal epithelium exposed to benzo[alfa]pyrene in organ culture

Roggebrand, R. (author), Wolterbeek, A.P.M. (author), van den Berg, P.T.M. (author), Rutten, A.A.J.J.L. (author), Feron, V.J. (author), Baan, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

The effect of benzo[a]pyrene (B[a]P) on cell proliferation in cultured hamster tracheal epithelium was studied in relation to the formation of B[a]P-DNA adducts. To this end, tracheae were isolated from Syrian golden hamsters, cut into rings and cultured in Ham's F12 medium. Then, the tracheal rings were exposed to 2 or 20 μM B[a]P, either...

article 1996

document

Local lymph node activation in rats after dermal application of the sensitizers 2,4-dinitrochlorobenzene and trimellitic anhydride

Arts, J.H.E. (author), Dröge, S.C.M. (author), Bloksma, N. (author), Kuper, C.F. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Five rat strains were compared for their performance in the local lymph node assay (LLNA) a promising test system for the identification of the skin-sensitizing potential of chemicals in the mouse. The contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and the contact and respiratory sensitizer trimellitic anhydride (TMA) were used as model...

article 1996

document

Regioselectivity and quantitative structure - Activity relationships for the conjugation of a series of fluoronitrobenzenes by purified glutathione S-transferase enzymes from rat and man

Soffers, A.E.M.F. (author), Ploemen, J.H.T.M. (author), Moonen, M.J.H. (author), Wobbes, T. (author), van Ommen, B. (author), Vervoort, J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Quantitative structure - activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes studied, the natural...

article 1996

document

Relevance of animal studies in regulatory toxicology: Current approaches and future opportunities

van de Sandt, J.J.M. (author), Feron, V.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

With rapidly increasing knowledge of toxicological processes, the scientific value and relevance of toxicity studies for risk assessment must be re-evaluated. In this paper, it is proposed that the rigid risk evaluation currently required should be replaced by a more flexible, case-by-case approach, in order to increase the relevance of each...

article 1996

document

Identification of multiple target sites for a glutathione conjugate on glutathione-S-transferase by matrix-assisted laser desorption/ionization mass spectrometry

Jespersen, S. (author), Ploemen, J.H.T.M. (author), Bladeren, P.J. (author), Niessen, W.M.A. (author), Tjaden, U.R. (author), van der Greef, J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

A mass spectrometric method providing qualitative site-specific information regarding covalent modification of proteins is described. The method involves comparison of unmodified and modified proteins by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) peptide mapping in combination with site-specific mutagenesis of...

article 1996

document

Inter-individual variability in the oxidation of 1,2-dibromoethane: Use of heterologously expressed human cytochrome P450 and human liver microsomes

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

document

Transport and metabolism of glutathione conjugates of menadione and ethacrynic acid in confluent monolayers of rat renal proximal tubular cells

Haenen, H.E.M.G. (author), Spenkelink, A. (author), Teunissen, C. (author), Temmink, J.H.M. (author), Koeman, J.H. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Confluent monolayers of primary rat renal proximal tubular (RPT) cells were used to compare transepithelial transport and concomitant metabolism of two different glutathione (GSH) S-conjugates. For the GSH-conjugated quinone compound, [35S]GSH-conjugated menadione (MGNQ), no specific transepithelial transport was observed. Most likely, [35S]MGNQ...

article 1996

document

Cytotoxicity of 2-tert-butyl hydroquinone glutathione conjugates after apical and basolateral exposure of rat renal proximal tubular cell monolayers

Haenen, H.E.M.G. (author), Bleijlevens, E. (author), Elzerman, H. (author), Temmink, J.H.M. (author), Koeman, J.H. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Confluent monolayers of renal proximal tubular (RPT) cells cultured on porous supports were used to investigate the cytotoxicity induced by glutathione conjugates of 2-tert-butyl-(1,4)-hydroquinone (SG-TBHQ) after apical and basolateral exposure. As judged from lactate dehydrogenase (LDH) leakage, cytotoxicity was observed after basolateral...

article 1996

document

Increased immunoreactivity and protein tyrosine kinase activity of the protooncogene pp60c-src in preneoplastic lesions in rat pancreas

Visser, C.J.T. (author), Rijksen, G. (author), Woutersen, R.A. (author), de Weger, R.A. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

This study investigates the possibility that the c-Src protein tyrosine kinase is involved in experimental exocrine pancreatic carcinogenesis. Expression and activity of the protooncogene pp60c-src (c-Src) are investigated in acinar pancreatic (pre-) neoplastic lesions induced in rats by azaserine and compared with normal rat pancreas. Low or...

article 1996

document

Cell proliferation and apoptosis in the exocrine pancreas of azaserine-treated rats and N-nitrosobis(2-oxopropyl)amine-treated hamsters: Effects of dietary fish oil

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

Altered cell proliferation is an important characteristic of neoplastic development, hence the quantitation of cell growth in normal and (pre)neoplastic pancreatic tissue will provide useful information on the process (and modulation) of pancreatic tumour promotion in experimental animals. Cell proliferation was estimated by means of BrdU...

article 1996

document

Comprehensive neurotoxicity assessment

Kulig, B.M. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Significant progress has been made in recent years in terms of both the conceptualization of neurotoxicity assessment strategies as well as in the development of behavioral techniques for evaluating neurotoxic exposures. A tiered approach, for example, has been advocated as an assessment strategy in which testing would proceed in a stepwise...

article 1996

document

The use of biokinetics and in vitro methods in toxicological risk evaluation: The report and recommendations of ECVAM workshop 15(1,2)

Blaauboer, B.J. (author), Bayliss, M.K. (author), Castell, J.V. (author), Evelo, C.T.A. (author), Frazier, J.M. (author), Groen, K. (author), Gülden, M. (author), Guillouzo, A. (author), Hissink, A.M. (author), Houston, J.B. (author), Johanson, G. (author), de Jongh, J. (author), Kedderis, G.L. (author), Reinhardt, C.A. (author), van de Sandt, J.J.M. (author), Semino, G. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

article 1996

document

The chicken enucleated eye test (CEET): A practical (pre)screen for the assessment of eye irritation/corrosion potential of test materials

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