The within- and between-laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative method that focuses on protein binding as the molecular initiating event for skin sensitization. It is a simple and versatile method that has successfully solved some of the problems of the direct peptide reactivity assay (DPRA). The transferability and within- and between-laboratory reproducibility of ADRA were evaluated and confirmed as part of a validation study conducted at four participating laboratories. The transfer of ADRA technology from the lead laboratory to the four participating laboratories was completed successfully during a two-step training program, after which the skin sensitization potentials of 40 coded chemicals were predicted based on the results of ADRA testing. Within-laboratories reproducibility was 100% (10 of 10), 100% (10 of 10), 100% (7 of 7) and 90% (9 of 10), or an average of 97.3% (36 of 37); between-laboratory reproducibility as calculated on the results of three laboratories at the time was 91.9%. The overall predictive capacity comprised an accuracy of 86.9%, sensitivity of 81.5% and specificity of 98.1%. These results satisfied the targets set by the validation management team for demonstrating transferability, within- and between-laboratory reproducibility, and predictive capacity as well as gave a clear indication that ADRA is easily transferable and sufficiently robust to be used in place of DPRA.

"I'm not going to make a song and dance about it...".

Having been involved with the biomedical sciences and alternatives for 30 of the 50 years since Russell and Burch published The Principles of Humane Experimental Technique, I feel well placed to speak of the contributions made by FRAME over the last 40 years. FRAME has promoted the development and use of alternatives by presenting the "better science" arguments to scientists, promoting informed discussion, changing opinions and changing behaviours. FRAME has also contributed constructively to the political debate, and was instrumental in promoting legislation which incorporated the principles of the Three Rs. Times are changing, and the Three Rs are increasing being politicised: and FRAME is particularly well placed to ensure that good science and good welfare, rather than ideology, remain the basis for interest in and progress with the Three Rs.

Report of the Working Group on Animal Distress in the Laboratory.

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

Animal use in the United Kingdom in 2001.

The United Kingdom publishes detailed, descriptive, annual statistical reports on the use of animals for experimental and other scientific purposes. This paper describes the method by which the statistics are compiled and the nature of the information collected. It provides a brief overview of the number of animals used, the patterns of use, and key trends for calendar year 2001. The limitations of the published data, and other classes of information that should be provided, are discussed.

Humane regulatory testing: the United Kingdom experience.

Regulatory testing requirements are considered by some to be rigid and inflexible. In fact, there is often considerable discretion in the animal test requirements and the endpoints that can be applied. This paper reviews the steps taken by government departments, agencies and professional associations in the UK to ensure that the Three Rs are reflected when animal testing is undertaken to satisfy regulatory requirements. The Home Office and other relevant government departments and agencies have agreed upon and implemented concordats on animal welfare and data sharing, and a joint guidance on humane regulatory testing has been published with the assistance of appropriate professional bodies. This paper describes these initiatives and reviews their impact to date on policy and practice at home and abroad.

Xenotransplantation: a European perspective.

A transnational approach is clearly the best way for the ethical and public health issues surrounding xenotransplantation to be discussed and coordinated policies formulated. However, the inertia involved in such processes, at a time of developments in the research underpinning xenotransplantation, conspire to ensure that there is always likely to be a lag between technical progress and regulatory developments. Although individual regions and nations are under pressure to address some of these issues, local and regional policy development must not lose sight of the need for a global strategy.

Refinement, reduction, and replacement of animal use for regulatory testing: future improvements and implementation within the regulatory framework.

Many are critical of how regulatory testing practices have evolved and become established--critical both of the scientific rational and the animal welfare costs. The test of whether we are more enlightened than our predecessors will be whether, armed with more powerful scientific insights and a better understanding of animal welfare, we can ensure that the best animal welfare and the best science drive and shape future developments in regulatory testing. Conducting the most humane animal-based regulatory testing requires establishing and maintaining a constructive dialogue between stakeholders and acknowledging the common ground that unites. Inclusive processes with stakeholders prepared to offer public, rational justifications for their policies and processes are essential if best practice is to be identified and implemented. There is general agreement that the best animal welfare results in the best science; that regulatory requirements based on an understanding of mechanisms and early relevant biomarkers result in elegant and valid science. Thus, "alternative" methods enabling replacement, reduction, or refinement (the 3Rs) are in reality often more scientifically "advanced" and scientifically valid methods. These principles provided the incentive and framework for recent initiatives in the United Kingdom to enhance the quality of the data prepared for regulatory submission while better protecting the welfare of the animals used. Some remaining 3R opportunities are explored in this paper, and some of the commonly encountered myths about regulatory testing and perceived barriers to change are challenged. Current "threats" may indeed offer opportunities for ensuring that sound science and the best animal welfare underpin developments in regulatory testing.