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Krishnan, S. (author), Vermeulen, R. (author), Pronk, A. (author), Gyori, B.M. (author), Bachman, J.A. (author), Vlaanderen, J. (author), Stierum, R. (author)BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated...article 2022
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Sewell, F. (author), Strupp, C. (author), van der Laan, J.W. (author), Wolf, D.C. (author), Wolterink, G. (author), Woutersen, R. (author), Zvonar, Z. (author), Heusinkveld, H. (author), Braakhuis, H. (author)Currently the only methods for non-genotoxic carcinogenic hazard assessment accepted by most regulatory authorities are lifetime carcinogenicity studies. However, these involve the use of large numbers of animals and the relevance of their predictive power and results has been scientifically challenged. With increased availability of innovative...article 2020
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Braakhuis, H.M. (author), Slob, W. (author), Olthof, E.D. (author), Wolterink, G. (author), Zwart, E.P. (author), Gremmer, E.R. (author), Rorije, E. (author), van Benthem, J. (author), Woutersen, R. (author), van der Laan, J.W. (author), Luijten, M. (author)Non-genotoxic carcinogens (NGTXCs) do not cause direct DNA damage but induce cancer via other mechanisms. In risk assessment of chemicals and pharmaceuticals, carcinogenic risks are determined using carcinogenicity studies in rodents. With the aim to reduce animal testing, REACH legislation states that carcinogenicity studies are only allowed...article 2018
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Reisinger, K. (author), Blatz, V. (author), Brinkmann, J. (author), Downs, T.R. (author), Fischer, A. (author), Henkler, F. (author), Hoffmann, S. (author), Krul, C. (author), Liebsch, M. (author), Luch, A. (author), Pirow, R. (author), Reus, A.A. (author), Schulz, M. (author), Pfuhler, S. (author)Recently revised OECD Testing Guidelines highlight the importance of considering the first site-of-contact when investigating the genotoxic hazard. Thus far, only in vivo approaches are available to address the dermal route of exposure. The 3D Skin Comet and Reconstructed Skin Micronucleus (RSMN) assays intend to close this gap in the in vitro...article 2018
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Woutersen, R.A. (author), Soffers, A.E.M.F. (author), Kroese, E.D. (author), Krul, C.A.M. (author), van der Laan, J.W. (author), van Benthem, J. (author), Luijten, M. (author)Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the...article 2016
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Luijten, M. (author), Olthof, E.D. (author), Hakkert, B.C. (author), Rorije, E. (author), van der Laan, J.-W. (author), Woutersen, R.A. (author), van Benthem, J. (author)Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer...article 2016
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Koster, S. (author), Leeman, W.R. (author), Verheij, E.R. (author), Dutman, A.E. (author), van Stee, L.L.P. (author), Munch Nielsen, L. (author), Ronsmans, S. (author), Noteborn, H. (author), Krul, L. (author)A main challenge in food safety research is to demonstrate that processing of foodstuffs does not lead to the formation of substances for which the safety upon consumption might be questioned. This is especially so since food is a complex matrix in which the analytical detection of substances, and consequent risk assessment thereof, is difficult...article 2015
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Koster, S. (author), Rennen, M. (author), Leeman, W. (author), Houben, G. (author), Muilwijk, B. (author), van Acker, F. (author), Krul, L. (author)One of the main challenges in food contact materials research is to prove that the presence of non-intentionally added substances (NIAS) is not a safety issue. Migration extracts may contain many unknown substances present at low concentrations. It is difficult and time-consuming to identify all these potential NIAS and concurrently to assess...article 2014
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Meunier, L. (author), Garthoff, J.A. (author), Schaafsma, A. (author), Krul, L. (author), Schrijver, J. (author), van Goudoever, J.B. (author), Speijers, G. (author), Vandenplas, Y. (author)Locust bean gum (LBG) is a galactomannan polysaccharide used as thickener in infant formulas with the therapeutic aim to treat uncomplicated gastroesophageal reflux (GER). Since its use in young infants below 12. weeks of age is not explicitly covered by the current scientific concept of the derivation of health based guidance values, the...article 2014
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Reus, A.A. (author), Usta, M. (author), Kenny, J.D. (author), Clements, P.J. (author), Pruimboom-Brees, I. (author), Aylott, M. (author), Lynch, A.M. (author), Krul, C.A.M. (author)An in vivo photomicronucleus test (MNT) using rat skin, the target organ for photoirritancy and carcinogenicity, was recently described. The assay was evaluated using fluoroquinolone (FQ) antibiotics with varying degrees of phototoxic potency (i.e. sparflocacin [SPFX], lomefloxacin [LOFX], ciprofloxacin [CIFX], levofloxacin [LEFX], gemifloxacin ...article 2012
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TNO Kwaliteit van Leven (author), Reus, A.A. (author), Usta, M. (author), Krul, C.A.M. (author)As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro...article 2012
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Heringa, M.B. (author), Harmsen, D.J.H. (author), Beerendonk, E.F. (author), Reus, A.A. (author), Krul, C.A.M. (author), Metz, D.H. (author), Ijpelaar, G.F. (author), TNO Kwaliteit van Leven (author)The objective of this study was to determine the genotoxic activity of water after UV/H<sub>2</sub>O<sub>2</sub> oxidation and GAC filtration. Pre-treated surface water from three locations was treated with UV/H<sub>2</sub>O<sub>2</sub> with medium pressure (MP) lamps and passed through granulated activated carbon (GAC). Samples taken before and...article 2011
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Savolainen, K. (author), Pylkkänen, L. (author), Norppa, H. (author), Falck, G. (author), Lindberg, H. (author), Tuomi, T. (author), Vippola, M. (author), Alenius, H. (author), Hämeri, K. (author), Koivisto, J. (author), Brouwer, D. (author), Mark, D. (author), Bard, D. (author), Berges, M. (author), Jankowska, E. (author), Posniak, M. (author), Farmer, P. (author), Singh, R. (author), Krombach, F. (author), Bihari, P. (author), Kasper, G. (author), Seipenbusch, M. (author), TNO Kwaliteit van Leven (author)The significance of engineered nanomaterials (ENM) and nanotechnologies grows rapidly. Nanotechnology applications may have a positive marked impact on many aspects of on human every day life, for example by providing means for the production of clean energy and pure drinking water. Hundreds of consumer nano-based products are already on the...article 2010
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Pfuhler, S. (author), Kirkland, D. (author), Kasper, P. (author), Hayashi, M. (author), Vanparys, P. (author), Carmichael, P. (author), Dertinger, S. (author), Eastmond, D. (author), Elhajouji, A. (author), Krul, C.A.M. (author), Rothfuss, A. (author), Schoening, G. (author), Smith, A. (author), Speit, G. (author), Thomas, C. (author), van Benthem, J. (author), Corvi, R. (author), TNO Kwaliteit van Leven (author)In vivo genetic toxicology tests measure direct DNA damage or the formation of gene or chromosomal mutations, and are used to predict the mutagenic and carcinogenic potential of compounds for regulatory purposes and/or to follow-up positive results from in vitro testing. These tests are widely used and consume large numbers of animals, with a...article 2009
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Casterton, P.L. (author), Curry, L.L. (author), Lina, B.A.R. (author), Wolterbeek, A.P.M. (author), Kruger, C.L. (author), TNO Kwaliteit van Leven (author)The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO...article 2009
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Ponstein-Simarro Doorten, A.Y. (author), van de Wiel, J.A.G. (author), Jonker, D. (author), TNO Kwaliteit van Leven (author)Tensguard™ is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard™ product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to...article 2009
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Adams, T.B. (author), Gavin, C.L. (author), Taylor, S.V. (author), Waddell, W.J. (author), Cohen, S.M. (author), Feron, V.J. (author), Goodman, J. (author), Rietjens, I.M.C.M. (author), Marnett, L.J. (author), Portoghese, P.S. (author), Smith, R.L. (author), TNO Kwaliteit van Leven (author), KvL (author)This publication is the 12th 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 flavoring substances under conditions of intended use. Since then, the number of flavoring...article 2008
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Vinken, M. (author), Doktorova, T. (author), Ellinger-Ziegelbauer, H. (author), Ahr, H.-J. (author), Lock, E. (author), Carmichael, P. (author), Roggen, E. (author), van Delft, J. (author), Kleinjans, J. (author), Castell, J. (author), Bort, R. (author), Donato, T. (author), Ryan, M. (author), Corvi, R. (author), Keun, H. (author), Ebbels, T. (author), Athersuch, T. (author), Sansone, S.-A. (author), Rocca-Serra, P. (author), Stierum, R. (author), Jennings, P. (author), Pfaller, W. (author), Gmuender, H. (author), Vanhaecke, T. (author), Rogiers, V. (author), TNO Kwaliteit van Leven (author)Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing...article 2008
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Adams, T.B. (author), McGowen, M.M. (author), Williams, M.C. (author), Cohen, S.M. (author), Feron, V.J. (author), Goodman, J.I. (author), Marnett, L.J. (author), Munro, I.C. (author), Portoghese, P.S. (author), Smith, R.L. (author), Waddell, W.J. (author), TNO Kwaliteit van Leven (author)This publication is the 11th 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 flavoring substances under conditions of intended use. The list of GRAS substances has now...article 2007
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Smith, R.L. (author), Cohen, S.M. (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), Hall, R.L. (author), Higley, N.A. (author), Lucas-Gavin, C. (author), Adams, T.B. (author), TNO Kwaliteit van Leven (author)A scientifically based guide has been developed to evaluate the safety of naturally occurring mixtures, particularly essential oils, for their intended use as flavor ingredients. The approach relies on the complete chemical characterization of the essential oil and the variability of the composition of the oil in the product intended for...article 2005