ECVAM Workshops: Summary of Conclusions and Recommendations

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-animaltest development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best way forward.To date, 19 workshops have been held, and reports of the first ten have been now published in ATLA (Alternatives to laboratory Animals). The main conclusions and recommendations given in these reports are outlined in this article.JRC.(EI)-Environment Institut

The Validation of Alternative Methods in Europe: The Role of ECVAM.

The European Commission established ECVAM in 1992 to coordinate the validation of alternative test methods at EU level. In 1995, based upon experience gained during several recent large-scale validation studies, and in consultation with various international experts, ECVAM published recommendations concerning the practical and logistical aspects of validating alternative test methods, and criteria which must be met before a test is considered ready to enter the validation process and those for evaluating the outcome of a validation study. These will be described in this presentation.JRC.(EI)-Environment Institut

Alternative Methods in Toxicological Research and Testing

Increasing public concern about the use of large numbers of animals in the safety evaluation of new chemicals and products has contributed, in part, to the development and evaluation of various non-animal methods in recent years. Several of these have been proposed as possible replacements for some of the animal procedures currently required in regulatory toxicity testing. In toxicological research, there has been a significant move away from whole animal studies, largely because of the application of cellular and molecular biology techniques. The development of appropriate in vitro test systems has enabled mechanistic studies to be undertaken, which cannot readily be carried out in living animals.JRC.(EI)-Environment Institut

Progress Toward the Validation of Alternative Tests

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.JRC.(EI)-Environment Institut

The Validation and Acceptance of Alternatives to Animal Testing.

Abstract not availableJRC.I-Institute for Health and Consumer Protection (Ispra

In Vitro Toxicology Studies with Human Keratinocities.

The application of human keratinocyte cultures in toxicological studies are described. In particular, studies concerned primarily with the development and evaluation of possible in vitro screens for detecting potential skin irritants, phototoxins, and tumour promoters are presented.JRC.(EI)-Environment Institut

The Role of Prevalidation in the Development, Validation and Acceptance of Alternative Methods

Experience has shown that the outcome of large and expensive validation studies on alternative methods can be compromised if their managers do not insist that optimised test protocols and proof of their performance are submitted before the start of the formal validation study. One way for the sponsors of validation studies to confirm both the likely relevance of a method for its stated purpose and its readiness for validation would be to require a prevalidation study before formal validation was contemplated. This process would involve the developers (or other proponents of the method) and selected indipendent laboratories in protocol refinement (Phase I) and protocol transfer (Phase II). The optimised protocol would then be assessed in a protocol performance phase (Phase III), which would involve the testing of a relevant set of coded test materials and an evolution of a proposed prediction model. In certain circumstances, a successful outcome of Phase III might be sufficient for promotion of the regulatory acceptance of the method. Normally, however, the method would proceed to a formal validation study. The European Centre for the Validation of Alternative Methods, a recognised validation authority, now proposes to introduce this prevalidation scheme into its validation strategy.JRC.(EI)-Environment Institut

Validation - Lessons Learned from Practical Experience

With regard to the problems encountered and the experience gained in validation studies conducted in the past, suggestions have been made concerning criteria for the selection of the tests and laboratories to be included in a validation study, the selection and distribution of test chemicals, and procedures for the handing, analysis and interpretation of the resulting ddata. In particular, tests should have been developed to the extent that detailed protocols and standards operating procedures have been produced and evaluated. The laboratories should be chosen on the basis of evidence of their appropriate experience, competence and ability to comply with good laboratory practice (GLP) requirements. The choise of test chemicals depends primarily on the goals of the validation study and on the availability of reliable in vitro toxicity data of high quality. A biostatistician should be involved in the initial design of the validationstudy as well as in the analysis of the resulting data. The quality of the in vivo and in vitro data must be ensured, prior to determining the reproducibility and predictivity of the alternative test.JRC.(EI)-Environment Institut

Alternative Methods for Skin Irritation Testing. The Current Status.

The following have been reviewed: (a) structure-activity and structure property relationships for skin corrosion and irritation; (b) the use of pH and acid-alkaline reserve measurementsin predicting skin corrosivity; (c) IN VITRO tests for skin corrosion; (d) IN VITRO tests for skin irritation (keratinocyte cultures, organ cultures, and reconstituted human skin models); and (e) human patch tests for skin irritation. It was apparent that, although several promising candidate IN VITRO tests for skin irritation (for example, reconstituted human skin methods, and human and animal skin organ culture methods) were under development and evaluation, a test protocol, preliminary prediction model and supporting data on different types of chemicals were only available for a method employing EpiDerm TM. Thus, it is proposed that this EpiDerm TM test undergoes prevalidation during1998. In addition, since it was felt preferable to be able to include other IN VITRO tests in such a prevalidation study, it is recommended that a "challenge" be set to anyone interested in taking part. This involves submitting data on 10 test chemicals to ECVAM, obtained according to a standard protocol with a preliminary prediction model, for review.JRC.(EI)-Environment Institut

The Validation of Toxicological Prediction Models.

An alternative method consists of two parts: the test system itself, and a prediction model for converting in vitro endpoints into predictions of in vivo toxicity. It is shown that there are certain circumstances in which a new prediction model can be introduced without the necessity to generate new test systems data.JRC.(EI)-Environment Institut