Validation ICCVAM

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). 

ICCVAM has validated three tests for dermal corrosion, including Corrositex , EPISKIN / EpiDerm, and Transcutaneous Electrical Resistance (TER). 

ICCVAM United States Interagency Coordinating Committee on the Validation... 

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. 

At the same time. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) evaluated FETAX methodology based on the inter-laboratory studies and published a review document in 2000 (5). The expert panel concluded that FETAX was not sufficiently validated for regulatory use due to the intra- and inter-laboratory variability (6). Nonetheless, the assay was developed in our laboratory for use as a predictive screening assay. 

ICCVAM evaluated the Frog Embryo Teratogenesis Assay— Xenopm (FETAX) as an alternative method for assessing developmental toxicity. In 2000, ICCVAM convened an expert panel and concluded that FETAX was not sufficiently validated or optimized for regulatory applications (31). Research using FETAX has been ongoing to address ICCVAM s recommendations that further standardization of the assay was necessary to improve variability and to expand the number of endpoints assessed to increase the performance of the assay. 

The National Institute of Environmental Health Sciences was directed by Public Law 103-43 to develop and validate alternative methods for acute and chronic toxicity testing. To implement this, they established an Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in 1997. 

The National Institute of Environmental Health Sciences was directed by Public Law 103-43 to develop and validate alternative methods for acute and chronic toxicity testing. To implement this, they established an Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in 1997. RBAs for the estrogen receptor vary considerably based on the source of the estrogen receptor proteins and isoforms (a or fS). Generally if the RBA for estradioTl7 S is set at 100, that of estrone is 15-60 and that of estriol is 0.2-30. 

The HET-CAM assay has been assessed in several validation studies including the EC/HO study, the COLIPAstudy, the German BMFT/BGA study, the CTFA study, collaborative studies carried out by cosmetic companies, the French OPAL study and the Japanese JMHW/JCI study [13]. In addition retrospective validation studies carried out by ICCVAM combined all existing information from previous studies and evaluated the usefulness of the assay to identify serious eye damage [54] as well as non-classified from classified chemicals [55], Regarding the identification of non-classified chemicals, due to the need for additional data, the assay was not found useful at that time by ICCVAM to be used for regulatory purposes for the evaluation of the eye hazards of chemicals [56],... 

The HET-CAM assay is regulatory accepted in the EU for the identification of serious eye damage [51]. It underwent a retrospective validation study carried out by ICCVAM which collected and combined the existing information from previous studies [54, 55]. For the identification of serious eye damage, further work was recommended before a statement on the scientific validity of the HET-CAM could be made [76, 77]. One potential reason for such outcome could be the variety of test protocols and prediction models that exist and which were used in the various validation studies. 

ICCVAM (2010) Test method evaluation report current validation status of in vitro test methods proposed for identifying eye injury hazard potential of chemicals and products. National Institutes of Health Publication Number 10-7553A. National Toxicology Program, North Carolina, USA. Available at http //iccvam.niehs.nih.gov/ methods/ocutox/Transmit-2010.htm. Accessed 31 July 2013... 

We might turn an argument around to substantiate the hypothesis that, especially in acute oral intoxications, the animals do not die from the toxin but from secondary effects to the GIT It has been documented in at least three major attempts, that cytotoxicity correlates pretty well with acute oral toxicity (see Halle register, MEIC study and the more recent ICCVAM/NICEATM/ECVAM validation study). Actually, this makes little sense if we assume that the substances are taken up, distributed and metabolized with complex kinetics and can affect more than 400 different tissues with various sensitivities. Might it be that the animal experiment simply measures cytotoxicity to the GIT epithelium, which results in translocation of bacteria Ironically, this would mean that we can pretty well predict this animal test in vitro, because the animal test measures a phenomenon (cytotoxicity to the intestine) that is irrelevant for humans (we would vomit—which rodents cannot do—or remove the intoxication before it reaches the intestine, supply intensive care treatment, etc.). Instead of our 9 million effort of A-Cute-Tox (http //www.acutetox.org/), a well-designed series of animal experiments might demonstrate that the reference method is meaningless. 

Clerici L et al (2006) Meeting report validation of toxicogenomics-based test systems ECVAM-ICCVAM/NICEAT M consider-... 

For example, a guideline approved in 2009 by the CAC defines a validated method as an accepted test method for which validation smdies have been completed to determine the accuracy and reliability of this method for a specific purpose, referencing a definition provided by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This definition is similar in content to definitions used by Eurachem, AOAC International, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), " and the VICH.19... 

At present there are no validated alternative methods able to completely replace the use of animals in the field of acute toxicity. Validation of an alternative model for acute oral toxicity is very complex and the time estimated to achieve complete animal replacement for acute toxicity is not clearly defined, nor can it be estimated at anything less than 10 years. However, there are some alternative methods currently available in different validation status prevalidated (MEIC, Multicenter Evaluation of in vitro cytotoxicity tests), under prevalidation (ECVAM), and validation (ECVAM, ICCVAM). 

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