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van Wezel, A.P. (author), van Lente, H. (author), van de Sandt, J.J.M. (author), Bouwmeester, H. (author), Vandeberg, R.L.J. (author), Sips, A.J.A.M. (author)Governments invest in “key enabling technologies,” such as nanotechnology, to solve societal challenges and boost the economy. At the same time, governmental agencies demand risk reduction to prohibit any often unknown adverse effects, and industrial parties demand smart approaches to reduce uncertainties. Responsible research and innovation ...article 2018
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Punt, A. (author), Schiffelers, M.J.W.A. (author), Jean Horbach, G. (author), van de Sandt, J.J.M. (author), Groothuis, G.M.M. (author), Rietjens, I.M.C.M. (author), Blaauboer, B.J. (author)The present paper aims at identifying strategies to increase the impact and applicability of alternative testing strategies in risk assessment. To this end, a quantitative and qualitative literature evaluation was performed on (a) current research efforts in the development of in vitro methods aiming for alternatives to animal testing, (b) the...article 2011
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Louisse, J. (author), Bai, Y. (author), Verwei, M. (author), van de Sandt, J.J.M. (author), Blaauboer, B.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA)...article 2010
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Louisse, J. (author), de Jong, E. (author), van de Sandt, J.J.M. (author), Blaauboer, B.J. (author), Woutersen, R.A. (author), Piersma, A.H. (author), Rietjens, I.M.C.M. (author), Verwei, M. (author), TNO Kwaliteit van Leven (author)At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells,...article 2010
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Buist, H.E. (author), van Burgsteden, J.A. (author), Freidig, A.P. (author), Maas, W.J.M. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)Most QSARs for dermal absorption predict the permeability coefficient, K<sub>p</sub>, of a molecule, which is valid for infinite dose conditions. In practice, dermal exposure mostly occurs under finite dose conditions. Therefore, a simple model to predict finite dose dermal absorption from infinite dose data (K<sub>p</sub> and lag time) and the...article 2010
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Buist, H.E. (author), Schaafsma, G. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual...article 2009
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Schaafsma, G. (author), Kroese, E.D. (author), Tielemans, E.L.J.P. (author), van de Sandt, J.J.M. (author), van Leeuwen, C.J. (author), TNO Kwaliteit van Leven (author)The objectives of REACH cannot be achieved under the current risk assessment approach. A change in mind set among all the relevant stakeholders is needed: risk assessment should move away from a labor-intensive and animal-consuming approach to intelligent and pragmatic testing, by combining exposure and hazard data effectively and trying to...article 2009
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de Jong, E. (author), Louisse, J. (author), Verwei, M. (author), Blaauboer, B.J. (author), van de Sandt, J.J.M. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Piersma, A.H. (author), TNO Kwaliteit van Leven (author)The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness...article 2009
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Arts, J.H.E. (author), Muijser, H. (author), Jonker, D. (author), van de Sandt, J.J.M. (author), Bos, P.M.J. (author), Feron, V.J. (author), TNO Kwaliteit van Leven (author)The OECD Health Effects Test Guidelines (TGs) provide guidance concerning the use of methods for the identification and characterization of hazards from chemical substances. These TGs are largely based on tests in routine use for many years and are known to yield information relevant to various types of toxicity. They have proven their value in...article 2008
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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...article 2008
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Gibbs, S. (author), van de Sandt, J.J.M. (author), Merk, H.F. (author), Lockley, D.J. (author), Pendlington, R.U. (author), Pease, C.K. (author), TNO Kwaliteit van Leven (author)In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential...article 2007
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- Meuling, W.J.A. (author), van de Sandt, J.J.M. (author), van Hemmen, J.J. (author), TNO Kwaliteit van Leven (author) article 2007
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Kroes, R. (author), Renwick, A.G. (author), Feron, V. (author), Galli, C.L. (author), Gibney, M. (author), Greim, H. (author), Guy, R.H. (author), Lhuguenot, J.C. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)The threshold of toxicological concern (TTC) has been used for the safety assessment of packaging migrants and flavouring agents that occur in food. The approach compares the estimated oral intake with a TTC value derived from chronic oral toxicity data for structurally-related compounds. Application of the TTC approach to cosmetic ingredients...article 2007
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Freidig, A.P. (author), Dekkers, S. (author), Verwei, M. (author), Zvinavashe, E. (author), Bessems, J.G.M. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in...article 2007
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- Buist, H.E. (author), Schaafsma, G. (author), van de Sandt, J.J.M. (author) article 2007
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Buist, H.E. (author), de Heer, C. (author), van Burgsteden, J.A. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)The in vitro dermal absorption kinetics of didecyldimethylammonium chloride (DDAC) was studied after single and multiple exposure. In addition, the influence of biocidal formulations on the absorption of DDAC was investigated. Following dermal exposure to DDAC in aqueous solution, less than 0.5% of the applied dose reached the receptor fluid...article 2007
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van de Sandt, J.J.M. (author), Dellarco, M. (author), van Hemmen, J.J. (author), TNO Kwaliteit van Leven (author)Exposure scenarios form an essential basis for chemical risk assessment reports under the new EU chemicals regulation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). In case the dermal route of exposure is predominant, information on both exposure and dermal bioavailability is necessary for a proper risk assessment....article 2007
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Wilkinson, S.C. (author), Maas, W.J.M. (author), Nielsen, J.B. (author), Greaves, L.C. (author), van de Sandt, J.J.M. (author), Williams, F.M. (author), TNO Kwaliteit van Leven TNO Voeding (author)Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P -0.01), testosterone ...article 2006
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Verwei, M. (author), van Burgsteden, J.A. (author), Krul, C.A.M. (author), van de Sandt, J.J.M. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)The new EU legislations for chemicals (Registration, Evaluation and Authorization of Chemicals, REACH) and cosmetics (Seventh Amendment) stimulate the acceptance of in vitro and in silico approaches to test chemicals for their potential to cause reproductive effects. In the current study seven compounds with known in vivo developmental effects...article 2006
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Schutte, M.E. (author), Freidig, A.P. (author), van de Sandt, J.J.M. (author), Alink, G.M. (author), Rietjens, I.M.C.M. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using...article 2006