Title

 

Authors

T. Hartung

Johns Hopkins University, School of Public Health, Center for Alternatives to Animal Testing, Doerenkamp-Zbinden Chair for Evidence-based Toxicology, Baltimore, USA

 

Abstract

The 3R concept to replace, reduce and refine animal experiments celebrated recently its 50^th anniversary. In the meantime, a mechanistic toxicology has evolved which is effectively relying to large extend on methodologies which substitute or complement traditional animal tests. The biotechnology and informatics revolution of the last decades has made such technologies broadly available and useful. Regulatory toxicology has only slowly begun to embrace these new approaches. Major validation efforts, however, have delivered the evidence that new approaches do not lower safety standards and can be integrated into regulatory safety assessments.
Political pressures especially in the EU, such as the REACH legislation and the 7^th amendment to the cosmetic legislation, further prompt the need of new approaches. In the US, especially the NAS vision report for a toxicology in the 21^st century and its most recent adaptation by EPA for their toxicity testing strategy have initiated a debate how to create a novel approach based on human cell cultures, lower species, high-throughput testing and modeling. A systematic mapping of the entirety of pathways of toxicity, the Human Toxome, has been started. 
The lecture summarizes the lessons learned from the development, validation and acceptance of alternative methods for the creation of a new approach for regulatory toxicology. The centers for alternatives to animal testing (CAAT) on both sides of the Atlantic promote this change with a number of activities. Beside the technical development of new approaches, a case is made that we need both conceptual steering and an objective assessment of current practices by evidence-based toxicology. It is suggested to apply an approach modeled on Evidence-based Medicine (EBM), which over the last two decades has demonstrated that rigorous systematic reviews of current practices and meta-analyses of studies provide powerful tools to provide health care professionals and patients with the current best scientific evidence for diagnostic and treatment options. Similarly, a portal for high-quality reviews of toxicological approaches and tools for the quantitative meta-analyses of data promise to serve as door opener for a new regulatory toxicology. The Evidence-based Toxicology Collaboration has been created in the US in 2011 and a European equivalent is in preparation.
  

Selected References
Griesinger C, Hoffmann S, Kinsner-Ovaskainen A, Coecke S and Hartung T. Proceedings of the First International Forum Towards Evidence-Based Toxicology. Conference Centre Spazio Villa Erba, Como, Italy. 15−18 October 2007. Human Exp Toxicol 2008, Special Issue: Evidence-Based Toxicology (EBT) 2009, 28:83-172.
Hartung T and McBride M. Food for thought… on mapping the human toxome. ALTEX 2011, 28, 83-93.
Hartung T. Lessons learned from alternative methods and their validation for a new toxicology in the 21st century. J. Toxicol. Env. Health 2010, 13:277-290.
Hartung T. From alternative methods to a new toxicology. Eur. J. Pharmaceutics Biopharmaceutics, 2011, 77:338–349.
Hartung T and Rovida C. Chemical regulators have overreached. Nature 2009, 460:1080-1081.
Hartung T. Toxicology for the twenty-first century. Nature 2009, 460:208-212.
Hartung T. A toxicology for the 21st century: Mapping the road ahead. Tox. Sci. 2009, 109:18-23.
Hartung T. Food for thought… on evidence-based toxicology. ALTEX 2009, 26:75-82.
Hartung T and Daston G. Are in vitro tests suitable for regulatory use? Tox. Sci. 2009, in 111:233-237.