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Consensus report on the future of animal-free systemic toxicity testing
Leist, M., N. Hasiwa, C. Rovida, M. Daneshian, D. Basketter, I. Kimber, H. Clewell, T. Gocht, A. Goldberg, F. Busquet, A. Rossi, M. Schwarz, M. Stephens, R. Taalman, T. Knudsen, J. McKim, G. Harris, D. Pamies, AND T. Hartung. Consensus report on the future of animal-free systemic toxicity testing. ALTEX. Society ALTEX Edition, Kuesnacht, Switzerland, 31(3):341-356, (2014).
This Join Report is on the scientific roadmap presented in the US-EU for animal-free testing (2011-12) in four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity, allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics).
This is a multi-authored consensus report from conferences held in 2011-2012. Complete author listing is as follows: Marcel Leist1,2, Nina Hasiwa1, Costanza Rovida1, Mardas Daneshian1, David Basketter3, Ian Kimber4, Harvey Clewell5, Tilman Gocht6, Alan Goldberg7, Derek Knight8, Gavin Maxwell9, Francois Busquet1, Anna-Maria Rossi1, Michael Schwarz6, Martin Stephens7, Rob Taalman10, Thomas B. Knudsen11, James McKim12, Georgina Harris7, David Pamies7, and Thomas Hartung1,71: Centre for Alternatives to Animal Testing, CAAT-Europe, University of Konstanz, Konstanz, Germany; 2: Doerenkamp-Zbinden Chair of in-vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany 3: DABMEB Consultancy Ltd, Sharnbrook, UK 4: Faculty of life Sciences, University of Manchester, UK 5. The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA 6: Eberhardt Karls University, Tübingen, Germany 7: Centre for Alternatives to Animal Testing, CAAT, John Hopkins University, Baltimore, US 8: European Chemicals Agency, Helsinki, Finland 9: Unilever, SEAC, Bedford, UK 10: Cosmetics Europe, Brussels, Belgium 11: US EPA, Research Triangle Park, NC, USA 12: CeeTox, Kalamazoo, MI, USA ABSTRACT: Since March 2013, animal use for cosmetics testing has been banned for the European market. This requires a renewed view on risk assessment in this field. However, also in other fields traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches has been outlined by the National Research Council (USA) vision document for a Toxicity Testing in the 21st Century in 2007 (NRC, 2007). It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity, allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics). CAAT-Europe has assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches, and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods, rather than favoring de novo design; combine hazard testing with toxicokinetics predictions; develop integrated test strategies; incorporate new high content endpoints to classical assays; evolve test validation procedures; promote collaboration and data-sharing of different industrial sectors, integrate new disciplines, such as systems biology and high throughput screening; and involve regulators early on in the test development process. Focus on data quality, combined with increased attention to the scientific background of a test method will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible adaptation to exposure scenarios and individual risk factors.