ATLA 25.1, January 1997

//ATLA 25.1, January 1997

Progress Toward the Validation of Alternative Tests

Michael Balls and Julia H. Fentem

ECVAM's role in the practical validation of replacement alternative methods for use in regulatory testing is reviewed, including an outline of the criteria which have been used in determining ECVAM's priorities. Some of the difficulties which have arisen in validation studies are discussed, and solutions to these are proposed, with particular emphasis on ensuring that methods are sufficiently well-developed to enter the validation process, and on the ECVAM prevalidation scheme for encouraging protocol optimisation and the prior assessment of interlaboratory transferability. Comments are made on problems encountered in selecting test materials backed by adequate in vivo data and in undertaking appropriate in vivo/in vitro comparisons.
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FRAME and the Pharmaceutical Industry

Robert Combes

Since its formation over 25 years ago, FRAME has worked closely with industry, academia, and legislative and regulatory bodies. Its aim is to actively promote the development, acceptance and validation of alternative methods which could reduce, refine or replace the use of laboratory animals in research, education and testing. FRAME has adopted a pragmatic and objective approach to laboratory animal welfare, underpinned by high-quality science.
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Pharmacokinetics in Early Drug Research

David E. Leahy, Ruth Duncan, Hans J. Ahr, Martin K. Bayliss, A. (Bert) G. de Boer, Ferenc Darvas, Julia H. Fentem, Jeffrey R. Fry, Robert Hopkins, J. Brian Houston, Johan Karlsson, Gregory L. Kedderis, Margaret K. Pratten, Pilar Prieto, Dennis A. Smith and Donald W. Straughan

This is the report of the twenty-second of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM’s main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures.
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Preselection of Potential Cancerostatics by Automatic Analysis of Suspended and Adherent Cells Incubated in Microplates

Walter Gutsche and Axel Stelzner

Alternative toxicological screening programmes, without the use of animal experiments, are intended to eliminate dangerous substances and to find new pharmacologically active agents in cell cultures. They can also provide information on the cytostatic activities of the agents. Intercalating cytostatics which bind DNA were selected by measuring the statistical distributions of the cell diameters of K-562 and L-929 cells by using an electronic cell analyser (CASY1). These compounds were identified by cell enlargement or from flat concentration–activity curves created with the cell analyser system. Incubation for 72 hours with DNA-binding agents, such as doxorubicin, daunorubicin and Mitoxantron®, resulted in enlargement of cell diameter and cell volume. The antineoplastic agents actinomycin D and ambazone had no comparable effect. Comparisons of the different parameters obtained with CASY1 measurement were performed with Microsoft EXCEL.
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Toxicity of 20 Chemicals from the MEIC Programme Determined by Growth Inhibition of L-929 Fibroblast-like Cells

Lena Järkelid, Per Kjellstrand, Evi Martinson and Anders Wieslander

The Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme is an international project aimed at evaluating the relevance of in vitro tests in predicting human toxicity. We have screened 20 chemicals (MEIC codes 31–50) from the programme, by using a cytotoxicity test based on growth inhibition of the mouse fibroblast-like L-929 cell line. Inhibition of cell growth was determined by the neutral red uptake method, which is well established and is used for screening the cytotoxicity of chemicals and plastics for pharmaceuticals and medical devices. The concentrations causing 50% inhibition of cell growth after a 72-hour exposure period varied from 3.1μM for hexachlorophene, to 1.4mM for caffeine. This is within the same range as results recently obtained with five other cell models. However, with some chemicals (chloroform, carbon tetrachloride and dichloromethane), no reliable results were obtained. These substances could not be dissolved in a reproducible way in any of the solvents used and, furthermore, they were highly volatile, which led to difficulties in maintaining the concentrations.
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Chimpanzees Should Not Be Used For Research On BSE

The Trustees of FRAME

As every week passes, it becomes more clear that the agent which causes BSE in cattle has been transmitted to other species, including man. However, it is still not possible to forecast accurately the scale of the threat to human beings, nor how long this threat will last. Meanwhile, despite this uncertainty, the farming industry is trying to restore the confidence of consumers, in order to protect the livelihoods of farmers and all who depend on them.
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