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T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays
Authors:Stefan F Martin  Philipp R Esser  Sonja Schmucker  Lisa Dietz  Dean J Naisbitt  B Kevin Park  Marc Vocanson  Jean-Francois Nicolas  Monika Keller  Werner J Pichler  Matthias Peiser  Andreas Luch  Reinhard Wanner  Enrico Maggi  Andrea Cavani  Thomas Rustemeyer  Anne Richter  Hermann-Josef Thierse  Federica Sallusto
Institution:1. Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany
2. Faculty of Biology, University of Freiburg, Freiburg, Germany
3. Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
4. Research Group for Immunology and Proteomics, Department of Dermatology and University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
5. Department of Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
6. Faculté de Médecine Lyon-Sud, INSERM U851, Université de Lyon1, Lyon, France
7. Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University Hospital and University of Bern, Bern, Switzerland
8. BfR-Federal Institute for Risk Assessment, Berlin, Germany
9. Institute of Molecular Biology and Bioinformatics, Charité, Berlin, Germany
10. Immunoallergology Unit, Policlinico di Careggi, Department of Internal Medicine, University of Florence, Florence, Italy
11. Laboratory of Immunology, Istituto Dermopatico dell’Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
12. Department of Dermatology, VU Medical Center, Amsterdam, The Netherlands
13. Institute for Research in Biomedicine, Bellinzona, Switzerland
Abstract:Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades.
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