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The potential of multi-organ-on-chip models for assessment of drug disposition as alternative to animal testing

van Berlo, D. (author), van de Steeg, E. (author), Amirabadi, H.E. (author), Masereeuw, R. (author)

The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In...

article 2021

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A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals

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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Development of a combined in Vitro Physiologically Based Kinetic (PBK) and Monte Carlo modelling approach to predict interindividual human variation in phenol-induced developmental toxicity

Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)

With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated...

article 2017

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A First Exploration of Health Impact Assessment of Chemical Exposure: Assigning Weights to Subclinical Effects Based on Animal Studies

ter Burg, W. (author), Bokkers, B.G.H. (author), Kroese, E.D. (author), Schuur, A.G. (author)

ABSTRACT: Health impact assessments (HIA) have become an important tool for applying evidence-based policy. Recently, the concept of HIA has been introduced in the field of chemical substances. Two main issues are encountered, i.e., the focus of risk assessment is deriving safe levels and on first signs of adverse effects. These adverse effects,...

article 2015

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Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Buist, H.E. (author), Devito, S. (author), Goldbohm, R.A. (author), Stierum, R.H. (author), Venhorst, J. (author), Kroese, E.D. (author)

Carbon capture and storage (CCS) technologies are considered vital and economic elements for achieving global CO2 reduction targets, and is currently introduced worldwide (for more information on CCS, consult for example the websites of the International Energy Agency (http://www.iea.org/topics/ccs/) and the Global CCS Institute (http://www...

article 2015

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State of the art on alternative methods to animal testing from an industrial point of view: Ready for regulation?

Ashton, R. (author), de Wever, B. (author), Fuchs, H.W. (author), Gaca, M. (author), Hill, E. (author), Krul, C.A.M. (author), Poth, A. (author), Roggen, E.L. (author)

Despite changing attitudes towards animal testing and current legislation to protect experimental animals, the rate of animal experiments seems to have changed little in recent years. On May 15–16, 2013, the In Vitro Testing Industrial Platform (IVTIP) held an open meeting to discuss the state of the art in alternative methods, how companies...

article 2014

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Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

Schiffelers, M.J.W.A. (author), Blaauboer, B.J. (author), Bakker, W.E. (author), Beken, S. (author), Hendriksen, C.F.M. (author), Koeter, H. (author), Krul, C.A.M. (author)

Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being...

article 2014

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Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human

Strikwold, M. (author), Spenkelink, B. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Punt, A. (author)

In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse...

article 2013

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Integrated in vitro-in silico models for predicting in vivo development toxicity: facilitating non-animal based safety asssment

Louisse, J. (author)

doctoral thesis 2012

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T4 report. An expert consortium review of the EC-commissioned report "Alternative (non-animal) methods for cosmetics testing: Current status and future prospects - 2010"

Hartung, T. (author), Blaauboer, B.J. (author), Bosgra, S. (author), Carney, E. (author), Coenen, J. (author), Conolly, R.B. (author), Corsini, E. (author), Green, S. (author), Faustman, E.M. (author), Gaspari, A. (author), Hayashi, M. (author), Hayes, A.W. (author), Hengstler, J.G. (author), Knudsen, L.E. (author), Knudsen, T.B. (author), McKim, J.M. (author), Pfaller, W. (author), Roggen, E.L. (author)

The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group of 17 independent experts from the US, Europe,...

article 2011

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Evaluation of research activities and research needs to increase the impact and applicability of alternative testing strategies in risk assessment practice

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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Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: Experience from Bulk Maritime Transport

Höfer, T. (author), James, D. (author), Syversen, T. (author), Bowmer, T. (author)

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory requirement for the carriage of bulk liquid...

article 2011

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Respiratory sensitization: Advances in assessing the risk of respiratory inflammation and irritation

Vandebriel, R. (author), Callant Cransveld, C. (author), Crommelin, D. (author), Diamant, Z. (author), Glazenburg, B. (author), Joos, G. (author), Kuper, F. (author), Natsch, A. (author), Nijkamp, F. (author), Noteborn, H. (author), Pieters, R. (author), Roberts, D. (author), Roggen, E. (author), Rorije, E. (author), Seed, M. (author), Sewald, K. (author), van den Heuvel, R. (author), van Engelen, J. (author), Verstraelen, S. (author), van Loveren, H. (author)

Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to...

article 2011

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REACH, non-testing approaches and the urgent need for a change in mind set

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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Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds

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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Inhalation toxicity studies: OECD guidelines in relation to REACH and scientific developments

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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The carcinoGENOMICS project: Critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays

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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Optimisation of the post-validation process: The report and recommendations of ECVAM workshop 67

Bottini, A.A. (author), Alepee, N. (author), Phillips, B. (author), Gribaldo, L. (author), de Silva, O. (author), Hartung, T. (author), Hendriksen, C. (author), Kuil, J. (author), Pazos, P. (author), Rhein, C. (author), Schiffelers, M.-J. (author), Stokes, W. (author), Theobald, A. (author), Vidal, J.-M. (author), van de Sandt, H. (author), Breier, S. (author), Sintes, J.R. (author), Blaauboer, B. (author), TNO Kwaliteit van Leven (author)

article 2008

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Physiologically-based kinetic modelling (PBK modelling): Meeting the 3Rs agenda. The report and recommendations of ECVAM workshop 63

Bouvier D'Yvoire, M. (author), Prieto, P. (author), Blaauboer, B.J. (author), Bois, F.Y. (author), Boobis, A. (author), Brochot, C. (author), Coecke, S. (author), Freidig, A. (author), Gundert-Remy, U. (author), Hartung, T. (author), Jacobs, M.N. (author), Lavé, T. (author), Leahy, D.E. (author), Lennernäs, H. (author), Loizou, G.D. (author), Meek, B. (author), Pease, C. (author), Rowland, M. (author), Spendiff, M. (author), Yang, J. (author), Zeilmaker, M. (author), TNO Kwaliteit van Leven (author)

article 2007

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Chemical respiratory allergy: Opportunities for hazard identification and characterisation

Kimber, I. (author), Agius, R. (author), Basketter, D.A. (author), Corsini, E. (author), Cullinan, P. (author), Dearman, R.J. (author), Gimenez-Arnau, E. (author), Greenwell, L. (author), Hartung, T. (author), Kuper, F. (author), Maestrelli, P. (author), Roggen, E. (author), Rovida, C. (author), Casati, S. (author), TNO Kwaliteit van Leven (author)

article 2007