ECVAM

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... 

With improvements in scientific knowledge and related technology, there is an expectation that more environmentally friendly pesticides will continue to be introduced, and that ecotoxicity testing procedures will become more sophisticated. There is much interest in the introduction of better testing procedures that work to more ecologically relevant end points than the lethal toxicity tests that are still widely used. Such a development should be consistent with the aims of organizations such as FRAME and ECVAM, which seek to reduce toxicity testing with animals. Mechanistic biomarker assays have the potential to be an important part of... 

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. 

Netzeva TI, Worth AP, Aldenberg T, Benigni R, Cronin MTD, Gramatica P et al. Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships. The report and recommendations of ECVAM workshop 52. ATLA 2005 33 152-73. 

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. 

An important point made by the ECVAM is that these three aspects 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. 

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. 

Worth AP, Balls M (eds) (2002) Alternative (non-animal) methods for chemicals testing current status and future prospects. A report prepared by ECVAM and the ECVAM working group on chemicals. ATLA 30(Suppl 1), pp 125... 

ECVAM (2010) Balb/c 3T33 Cell Transformation Assay - Prevalidation Study Report... 

Vanparys P, Schechtman L, Aardema M, Hayashi M, Hoffmann S, Gribaldo L, Corvi R (2010) Balb/c 3T3 Cell Transformation Assay - Prevalidation Study Report. ECVAM Balb/c 3T3 CTA PRP report vl - 30 July 2010... 

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). 

ECVAM European Centre for the Validation of PEC Predicted environmental concentration... 

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]. 

The following in vitro methods based on reconstructed human skin models are validated (by the ECVAM) for predicting skin corrosion— EPISKIN , EpiDerm , Corrositex —and irritation EPISKEM , EpiDerm , PREDISKIN , SIFT [142], Additionally, the SkinEthic was assessed and... 

ECVAM. News and Views. Statement on the scientific validity of the rat skin transcutaneous electrical resistance (TER) test (an in vitro test for skin corrosivity). ATLA 26 275-280 (1998). 

ECVAM. ECVAM News Views. Allern. Lab. Anim. 26 275-280 (1998). 

K. Meyer, C. Steinhoff, C. Tornier, B. De Wever, and M. Rosdy. Assessment of the skin irritation potential of chemicals by using the SkinEthic reconstructed human epidermal model and the common skin irritation protocol evaluated in the ECVAM skin irritation validation study. Altern. Lab. Anim. 34 393-406 (2006). 

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). 

ECVAM was created in response to a requirement in Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes, which requires that the EU Commission and the EU Member States should actively support the development, validation, and acceptance of methods, which could reduce, refine, or replace the use of laboratory animals. 

The duties of ECVAM are to coordinate the validation of alternative test methods at the EU level, to act as a focal point for the exchange of information on the development of alternative test methods, to set up, maintain, and manage a database on alternative procedures, and to promote dialogue between legislators, industries, biomedical scientists, consumer organizations, and animal welfare groups, with a view to the development, validation, and international recognition of alternative test methods. 

ECVAM has its own Scientific Advisory Committee (ESAC) with participation from all Member States, relevant industrial associations, academic toxicology, the animal welfare movement, as well as other Commission services with interest in the alternatives topic area. 

ECVAM has validated alternative test methods for acute oral toxicity, biologies, immunotoxicity, dermal corrosion and irritation, developmental toxicity, and pyrogenicity (ECVAM 2007). 

The following in vitro tests, replacing in vivo animal tests, have been endorsed as scientifically valid by ECVAM and have been adopted as EU test methods (EU 2006) ... 

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. 

Currently, there are no validated and regulatory accepted in vitro methods for assessing repeated dose toxicity. Numerous in vitro systems have been developed over the last decades and have been discussed and summarized in recent ECVAM reports on repeated dose toxicity testing (Worth and Balls 2002, Prieto et al. 2005, Prieto et al. 2006). Human in vitro data, particularly on kinetics and metabolism, and in vitro test data from well-characterized target organ and target system models on, e.g., mode of action(s)/mechanism(s) of toxicity may be useful in the interpretation of observed repeated dose toxicity. 

Prieto, P., A.W. Baird, B.J. Blaauboer, J.V. Castell Ripoll, et al. 2006. The assessment of repeated dose toxicity in vitro A proposed approach. The report and recommendations of ECVAM Workshop 56. ATLA 34 315-341. 

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

Toda, E., Tong, W., van Delft, J.H., Weis, B. and Schechtman, L.M. (2006) Validation of toxicogenomics-based test systems ECVAM-ICCVAM/NICEATM considerations for regulatory use. Environmental Health Perspectives, 114, 420-429. 

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