ECVAM Alternative Methods

European Centre for the Validation of Alternative Methods (ECVAM), six in vitro systems for chronic neurotoxicity testing are recommended for further consideration (Worth and Balls 2002). These are described as in vitro models that may be suitable for long-term toxicity testing. The systems are... 

Worth, A. and Balls, M. (Eds.) (2002). Alternative Methods for Chemicals Testing Current Status and Future Prospects. Ispra, Italy European Centre for the Vahdation of Alternative Methods(ECVAM), 71-74. 

In vitro tools could be used alone or in test batteries with increased potency of the description of cellular events and changes. The chapter provides a brief introduction on the components of an in vitro system, the main differences between models for research and models for testing and a list of validated alternative methods according to the European Centre for the Validation of Alternative Methods (ECVAM) (http // ecvam.jrc.it/, http //ecvam.jrc.ec.europa.eu/) evaluation. 

ECVAM as part of the JRC fulfills the task to validate alternative methods. Its advisory group ES AC advises ECVAM scientifically and gives expert judgment on the different proposed non-animal tests. 

An important point, made by the European Centre for the Validation of Alternative Methods (ECVAM), is that these 3 aspects (3Rs) should not be considered as alternatives that could replace each other, but as parts of an integrated system which should lead to progress in the development of non-animal tests and testing strategies. Another important key point recently defined by ECVAM is that the use of existing information must be maximized instead of testing methods. 

Alternative tests will have to be validated scientifically and established as acceptable by industry and the regulators before being used for registration. The EU body which undertakes this validation process is the European Centre for the Validation of Alternative Methods (ECVAM), and the US equivalent is the Interagency Co-ordinating Committee on the Validation of Alternative Methods (ICCVAM). 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

Le Ferrec E, Chesne C, Artursson P, Brayden D, Fabre G, Gires P, Guillou F, Rousset M, Rubas W, Scarino ML (2001) In vitro models of the intestinal barrier. The report and recommendations of ECVAM Workshop 46. European Centre for the Validation of Alternative methods. Altern Lab Anim 29 649-668. 

The European Center for the Validation of Alternative Methods (ECVAM) uses and evaluates toxicogenomics, among other methods, e.g., in its carcinogenicity program (ECVAM 2007). 

ECETOC. 2007b. European Centre for Ecotoxicology and Toxicology of Chemicals (publications) website http /www.ecetoc.org/Content/Default.asp PagelD = 21 ECVAM. 2007. European Center for Validation of Alternative Methods website. http /ecvam.jrc.it/index.htm EU. 2006. The DG Environment REACH website. http /ec.europa.eu/environment/chemicals/reach EU. 2007. European Commision, Research Science and Society website The role of ethics in EU research. 

ECVAM European Center for the Validation of Alternative Methods... 

The 35 mm dish assay detects compounds that are cytotoxic to or alter proliferation of the multipotent stem cells, but the main limitation of the 35 mm dish CFU assay is the need to microscopically identify and count the colonies to determine the compound concentration that decreased the number of colonies by 50% (IC50) or 90% (IC90). The European Community for Validation of Alternative Methods (ECVAM) supported the recommendation of using the mouse and human CFU-GM IC90 with... 

Right now, in Europe, there are three validated in vitro assays aimed at evaluating embryotoxicity (teratogenicity) potential. Three of these assays were submitted to extensive intra- and interlaboratory validations lead by the European Center for Validation of Alternative Methods (ECVAM) (3) ... 

Genschow E, Spiehnann H, Scholz G et al (2002) The ECVAM international validation study on in vitro embryotoxicity tests results of the definitive phase and evaluation of prediction models. European Centre for the Validation of Alternative Methods. Altern Lab Anim 30(2) 151-176... 

P.A. Botham, L.K. Earl, J.H. Fentem, R. Roguet, and J.J.M. van dc Sandt, Alternative Methods for Skin Irritation Testing The Current Status, ECVAM Skin Irritation Task Force Report 1, ATLA, 26, 195-211, 1998. 

One key issue is the requirement for animal testing. The report and recommendations of the European Centre for the Validation of Alternative Methods (ECVAM) workshop (Leahy et al., 1997) clearly state that a major priority is to reduce the number of animals used in pharmacokinetic studies in drug development. As much information as possible should be obtained from alternative sources, such as computer modeling or using data already generated for similar compounds. 

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),... 

Worth, A.P. and Balls, M., The role of ECVAM in promoting the regulatory acceptance of alternative methods in the European Union, Alternatives Lab. Anim., 29, 525-535, 2001. 

A European Centre for the Validation of Alternative Methods (ECVAM) was created by a Communication from the Commission to the Council and the Parliament in 1991, pointing to a requirement in Directive 86/609/EEC for the protection of animals used for experimental and other scientific purposes, which requires that the Commission and the Member States should actively support the development, validation, and acceptance of methods which could reduce, refine, or replace the use of laboratory animals [11]. As defined in the Communication of the European Commission to Council and the European Parliament, the duties of ECVAM are ... 

ECVAM seeks to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences, through research, new test development and validation, and the establishment of specialized databases, with the aim of contributing to the replacement, reduction, and refinement of laboratory... 

Last but not least there is an urgent need to "harmonize" or "standardize" all these procedures so that improved interlaboratory comparisons can be achieved. Such procedures include, cell isolation, growth substrates, cell culture media including the mode of medium application. A first initiative in this direction has been taken by ECVAM (European Center for the Validation of Alternative Methods, a section of the European Commission Institute for Health and Consumer Protection) by founding a task force dealing with the creation of guidelines for "Good Cell Culture Practice" [247, 248]. 

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