Integrated testing strategies

Blaauboer, B.J., Barratt, M.D., and Houston, J.B., The integrated use of alternative methods in toxicological risk evaluation — ECVAM Integrated Testing Strategies task force report 1, Alt. Lab. Anim. (ATLA),... 

Because of the limitations of individual alternative (non-animal) methods for predicting toxicological hazard, there is a growing emphasis on the use of integrated approaches that combine the use of two or more alternative tests. This has led to the concept of the integrated testing strategy, which has been defined as follows (Blaauboer et al., 1999) ... 

An integrated testing strategy is any approach to the evaluation of toxicity which serves to reduce, refine or replace an existing animal procedure, and which is based on the use of two or more of the following physicochemical, in vitro, human (e.g., epidemiological, clinical case reports), and animal data (where unavoidable), and computational methods, such as (quantitative) structure-activity relationships ([Q]SAR) and biokinetic models. 

Since integrated testing strategies are based on the use of different types of information, they are expected to be particularly successful at predicting in vivo end points that are too complex in biochemical and physiological terms for any single method to reproduce. 

R.D. Combes, Prospects for using Data from (Q)SARs and Expert Systems in Integrated Testing Strategies for the Risk Assessment of Chemicals, Silico AMET Design of Bioactive Compounds, SCI Conference, London, UK, 2005. 

Besides the test methods described in Section 3 as being able to identify non-classified materials (BCOP, ICE and CM), a number of advanced in vitro test methods have been proposed for the identification of non-classified materials from classified ones (GHS Cat. 1 and Cat. 2). These methods are considered useful within integrated test strategies and in particular for initiating the bottom-up approach to accurately identify non-classified materials. 

The in vitro integrated testing strategy (ITS) had a sensitivity of 87 %y a specificity of... 

Jaworska J, Dancik Y, Kern P, Gerberick F, Natsch A (2013) Bayesian integrated testing strategy to assess skin sensitization potency from theory to practice. J Appl Toxicol... 

Hartung T, Luechtefeld T, Maertens A, Kleensang A (2013) Integrated testing strategies for safety assessments. ALTEX 30 3-18... 

Doktorova TY, Pauwels M, Vinken M, Vanhaecke T, Rogiers V (2012) Opportunities for an alternative integrating testing strategy for carcinogen hazard assessment Crit Rev Toxicol 42 91-106... 

Several of the validated in vitro methods aim to be validated as full replacement methods to offer an alternative for in vivo test guideline method(s). However, for integrated testing strategies, validated mechanistic tools targeting key events in adverse outcome pathways are necessary to generate state-of-the-art alternative approaches to conventional toxicological test methods based on laboratory animals. 

In this book, we attempt to bring together the important issues and considerations we believe are needed in order to develop a workable, reliable, integrated testing strategy for the replacement of animals in toxicity testing regimes. 

The NRPCT integrated testing strategy was to use the existing national infrastructure (NASA Centers, national DOE labs, etc.) whenever possible to minimize cost and lead time. 

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