non-animal methods

/Tag:non-animal methods

Evaluation of Non-animal Methods for Assessing Skin Sensitisation Hazard: A Bayesian Value-of-Information Analysis

Leontaridou_suppl_info_FINAL

Maria Leontaridou, Silke Gabbert, Ekko C. Van Ierland, Andrew P. Worth and Robert Landsiedel

This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the development of non-animal testing strategies, balancing information gains from testing with the expected social gains and costs from the adoption of regulatory decisions. Testing is assumed to have value, if, and only if, the information revealed from testing triggers a welfare-improving decision on the use (or non-use) of a substance. As an illustration, our VOI model is applied to a set of five individual non-animal prediction methods used for skin sensitisation hazard assessment, seven battery combinations of these methods, and 236 sequential 2-test and 3-test strategies. Their expected values are quantified and compared to the expected value of the local lymph node assay (LLNA) as the animal method. We find that battery and sequential combinations of non-animal prediction methods reveal a significantly higher expected value than the LLNA. This holds for the entire range of prior beliefs. Furthermore, our results illustrate that the testing strategy with the highest expected value does not necessarily have to follow the order of key events in the sensitisation adverse outcome pathway (AOP).

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Animal Experimentation and Alternatives: Time to Say Goodbye to the Three Rs and Hello to Humanity?

Michael Balls

The time has come to plan for a future where the Three Rs will have served their purpose, animal experimentation will have been consigned to history, and humane biomedical science in research, testing and education will have become the norm, for the benefit of humans and animals alike.

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Report of the EPAA–ECVAM Workshop on the Validation of Integrated Testing Strategies (ITS)

Agnieszka Kinsner-Ovaskainen, Gavin Maxwell, Joachim Kreysa, João Barroso, Els Adriaens, Nathalie Alépée, Ninna Berg, Susanne Bremer, Sandra Coecke, José Z. Comenges, Raffaella Corvi, Silvia Casati, Gianni Dal Negro, Monique Marrec-Fairley, Claudius Griesinger, Marlies Halder, Eckhard Heisler, Doris Hirmann, André Kleensang, Annette Kopp-Schneider, Silvia Lapenna, Sharon Munn, Pilar Prieto, Len Schechtman, Terry Schultz, Jean-Marc Vidal, Andrew Worth and Valérie Zuang

The use of Integrated Testing Strategies (ITS) permits the combination of diverse types of chemical and toxicological data for the purposes of hazard identification and characterisation. In November 2008, the European Partnership for Alternative Approaches to Animal Testing (EPAA), together with the European Centre for the Validation of Alternative Methods (ECVAM), held a workshop on Overcoming Barriers to Validation of Non-animal Partial Replacement Methods/Integrated Testing Strategies, in Ispra, Italy, to discuss the extent to which current ECVAM approaches to validation can be used to evaluate partial replacement in vitro test methods (i.e. as potential ITS components) and ITS themselves. The main conclusions of these discussions were that formal validation was only considered necessary for regulatory purposes (e.g. the replacement of a test guideline), and that current ECVAM approaches to validation should be adapted to accommodate such test methods (1). With these conclusions in mind, a follow-up EPAA–ECVAM workshop was held in October 2009, to discuss the extent to which existing validation principles are applicable to the validation of ITS test methods, and to develop a draft approach for the validation of such test methods and/or overall ITS for regulatory purposes. This report summarises the workshop discussions that started with a review of the current validation methodologies and the presentation of two case studies (skin sensitisation and acute toxicity), before covering the definition of ITS and their components, including their validation and regulatory acceptance. The following main conclusions/recommendations were made: that the validation of a partial replacement test method (for application as part of a testing strategy) should be differentiated from the validation of an in vitro test method for application as a stand-alone replacement, especially with regard to its predictive capacity; that, in the former case, the predictive capacity of the whole testing strategy (rather than of the individual test methods) would be more important, especially if the individual test methods had a high biological relevance; that ITS allowing for flexible and ad hoc approaches cannot be validated, whereas the validation of clearly defined ITS would be feasible, although practically quite difficult; and that test method developers should be encouraged to develop and submit to ECVAM not only full replacement test methods, but also partial replacement methods to be placed as parts of testing strategies. The added value from the formal validation of testing strategies, and the requirements needed in view of regulatory acceptance of the data, require further informed discussion within the EPAA forum on the basis of case studies provided by industry.

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A Vision Becoming Reality

Gill Langley

Non-animal science in toxicology and health research has been progressing for decades, but
only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.
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