ATLA::Alternatives to Laboratory Animals

Volume 27, Number 2

The integrated use of alternative methods in toxicological risk evaluation.
ECVAM Integrated Testing Strategies Task Force Report 1

ATLA 27, 229-238, March/April 1999

Bas J. Blaauboer,1 Martin D. Barratt2 and J. Brian Houston3

1Research Institute of Toxicology, Utrecht University, 3508 TD Utrecht, The Netherlands; 2Marlin Consultancy, 10 Beeby Way, Carlton, Bedford MK43 7LW, UK; 3School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester M13 9PL, UK

SUMMARY

The ECVAM Task Force on Integrated Testing Strategies was established in December 1996, with the remit of assessing the current status of integrated toxicity testing, and of making proposals regarding the design and implementation of integrated testing strategies. The first step in an integrated testing strategy is usually to determine the chemical functionality of a substance, on the basis of its structure and physicochemical properties. The biokinetic and dynamic behaviours of the chemical in various in vitro systems are then assessed. The various elements are then integrated, in either a parallel or a step-wise fashion, to make predictions of the local or systemic toxicity of the chemical of interest. In this report, a generic scheme for local/systemic toxicity, and a specific scheme for target organ toxicity, are proposed. The scope end limitations of the approaches are discussed. The task force hopes that its proposals will stimulate a discussion on the feasibility of this type of approach and it welcomes any feedback. It is planned that the discussion points will be elaborated in a second task force report.

Keywords: chemical, toxicity, toxicological, assessment, testing strategy, integrated, parallel, step-wise, hierarchical