Atla-alternatives To Laboratory Animals 

About: Atla-alternatives To Laboratory Animals is an academic journal published by Fund for the Replacement of Animals in Medical Experiments. The journal publishes majorly in the area(s): European union & Cell culture. It has an ISSN identifier of 0261-1929. Over the lifetime, 2033 publications have been published receiving 31508 citations. The journal is also known as: Alternatives to laboratory animals & Alternatives to Laboratory Animals.

Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships. The report and recommendations of ECVAM Workshop 52.

Abstract: This is the 52nd report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main objective of ECVAM, 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 that reduce, refine or replace the use of laboratory animals. The ECVAM workshop on the quantitative structure-activity relationship applicability domain was held at ECVAM on 29 September–1 October 2004, under the chairmanship of Andrew Worth. The workshop was attended by experts from academia, industry, international organisations and regulatory authorities. The aim of the workshop was to review the state of the art of methods for identifying the domain of applicability of structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), collectively referred to as (Q)SARs. The report is intended to provide a source of input to the development of an OECD Guidance Document on (Q)SAR Validation. The report also makes recommendations for further research needed to understand and apply the concept of the (Q)SAR applicability domain (AD).

A multicompartmental dynamic computer-controlled model simulating the stomach and small intestine

Abstract: A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of t...

QSAR Applicability Domain Estimation by Projection of the Training Set in Descriptor Space: A Review:

Abstract: As the use of Quantitative Structure Activity Relationship (QSAR) models for chemical management increases, the reliability of the predictions from such models is a matter of growing concern. The OECD QSAR Validation Principles recommend that a model should be used within its applicability domain (AD). The Setubal Workshop report provided conceptual guidance on defining a (Q)SAR AD, but it is difficult to use directly. The practical application of the AD concept requires an operational definition that permits the design of an automatic (computerised), quantitative procedure to determine a models AD. An attempt is made to address this need, and methods and criteria for estimating AD through training set interpolation in descriptor space are reviewed. It is proposed that response space should be included in the training set representation. Thus, training set chemicals are points in n-dimensional descriptor space and m-dimensional model response space. Four major approaches for estimating interpolation regions in a multivariate space are reviewed and compared: range, distance, geometrical, and probability density distribution.

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

Abstract: From 1996 to 2000, ZEBET (Centre for Documentation and Evaluation of Alternative Methods to Animal Experiments at the BgVV, Berlin, Germany) coordinated the European Centre for the Validation of Alternative Methods (ECVAM) prevalidation and validation study on three embryotoxicity tests: a) a test employing embryonic stem cell lines (EST); b) the micromass (MM) test; and c) the postimplantation rat whole-embryo culture assay (WEC test). The main objectives of the study were to assess the performance of these three in vitro tests in discriminating between non- embryotoxic, weakly embryotoxic and strongly embryotoxic compounds. Phase I of the study (1997) was designed as a prevalidation phase, for test protocol optimisation, and for the establishment of a comprehensive database of in vivo and in vitro data on embryotoxic compounds. Phase II (1998-2000) involved a formal validation trial, conducted under blind conditions on 20 test compounds selected from the database, which were coded and distributed to the participating laboratories. In the preliminary phase of the validation study, six chemicals out of the 20, which showed embryotoxic potential, were tested. These results were used to define new biostatistically based prediction models (PMs) for the MM and WEC tests, and to evaluate those developed previously for the EST. As a next step, the PMs were evaluated by using the results for the remaining 14 chemicals of the definitive phase of the validation study. The three in vitro embryotoxicity tests proved to be applicable to testing a diverse group of chemicals with different embryotoxic potentials (non-embryotoxic, weakly embryotoxic, and strongly embryotoxic). The reproducibility of the three in vitro embryotoxicity tests were acceptable according to the acceptance criteria defined by the Management Team. The concordances between the embryotoxic potentials derived from the in vitro data and from the in vivo data were good for the EST and the WEC (PM2) test, and sufficient for the MM test and the WEC (PM1) tests according to the performance criteria defined by the Management Team before the formal validation study. When applying the PM of the EST to the in vitro data obtained in the definitive phase of the formal validation study, chemicals were classified correctly in 78% of the experiments. For the MM and the WEC tests, the PMs provided 70% and 80% (PM2) correct classifications, respectively. And, very importantly, an excellent predictivity (100%, except for PM1 of the WEC test, with 79%, considered as good) was obtained with strong embryotoxic chemicals in each of the three in vitro tests.

Validation of the embryonic stem cell test in the international ECVAM validation study on three in vitro embryotoxicity tests.

Abstract: A detailed report is presented on the performance of the embryonic stem cell test (EST) in a European Centre for the Validation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects in animals and/or humans, were tested in four laboratories. The outcome showed that the EST can be considered to be a scientifically validated test, which is ready for consideration for use in assessing the embryotoxic potentials of chemicals for regulatory purposes.