Biomedical subjects

M Balls

Publications and source records attributed to M Balls.

At least 19 recordsLinked to original sources

PubMed2002

Progress in applying the three Rs of Russell & Burch to the testing of biological products.

The Three Rs (Reduction, Refinement, Replacement) concept of Russell & Burch in relation to humane laboratory animal experimentation is introduced, and special aspects concerning the testing of biologicals are outlined. The role of ECVAM in promoting the Three Rs in the European Union, by organising workshops and task forces, supporting conferences, and financing and/or participating in alternative test development, pre-validation and validation, is reviewed. Finally, examples are given of biologicals-related issues which deserve attention or greater focus.

Advisory Committees↗

PubMed2002

Implementation of three Rs alternatives in regulatory testing: possibilities and obstacles--the view of the validator.

After the establishment of the European Centre for the Validation of Alternative Methods (ECVAM) in 1993, the Scientific Advisory Committee (ESAC) decided at its first meeting that the implementation of the Three Rs in the production and quality control of biologicals should be one of ECVAMs priorities. In collaboration with experts, ECVAM has established guidelines on the pre-validation and validation of alternative toxicological methods, which are as applicable to alternative methods in the quality control of biologicals as they are to the testing of industrial chemicals. This paper explains the technical information which should be submitted to ECVAM to assess the readiness of a method for pre-validation, which is defined as a small-scale interlaboratory study to confirm that an optimised and transferable protocol is available. Where appropriate, a formal validation study is then conducted, to evaluate the scientific relevance and reliability of the test method.

Animal Testing Alternatives↗

PubMed2001

Promotion of research on in vitro immunotoxicology.

ECVAM was established to play a leading role at the European level in the independent evaluation of the reliability and relevance of test methods and testing strategies for specific purposes through research on advanced methods and new test development and validation, so that chemicals and products of various kinds, including medicines, vaccines, medical devices, cosmetics, household products and agricultural products, can be manufactured, transported and used more economically and more safely, whilst the current relevance on animal test procedures is progressively reduced. Nowhere is this activity more necessary than in the field of immunotoxicology, where we know that chemicals and products of many kinds have the potential to stimulate, modulate or suppress the induction or expression of various types of immune responses. The problem is to effectively evaluate the potency of these effectors, and, since the available information is currently based on rather qualitative animal tests, to evaluate the true relevance of this knowledge and apply it intelligently in risk assessment processes which will protect human beings without unnecessarily limiting the development and use of materials which otherwise have economic, health and social benefits. The way forward must depend on the following: (a) a better understanding of immunotoxicological processes, based on a sounder understanding of the immune system itself (and of its network of control systems and interrelationships with other body systems); (b) The use of in vitro (not in vivo) systems based on human (not animal) cells and tissues; (c) integrated and tiered testing strategies, incorporating QSAR, as well as in vitro approaches; (d) taking advantage of the use of cells or factors from humans who have been exposed to potential immunotoxins, be this voluntarily, occupationally, environmentally or by accident; and (e) the recognition that virtually everything will effect one or more aspects of the immune system at some dose level and, in some circumstances, deciding when such effects are relevant, is the key to immunotoxicity testing. Some current ECVAM-sponsored work and activities at ECVAM are described.

Academies and Institutes↗

PubMed2001

Establishment of an in vitro reporter gene assay for developmental cardiac toxicity.

This study is based on the unique potential of pluripotent embryonic stem (ES) cells to differentiate in vitro into embryoid bodies containing cell lineages representative of most cell types found in the mammalian fetus. However, the use of wild type ES cells as an in vitro assay for embryotoxicological studies is complicated by the simultaneous development of various cellular phenotypes. This prevents a quantitative assessment of drug effects on one specific cell type. Here we report the effects of 15 chemicals on cardiac differentiation as determined by various specific toxicological endpoints such as morphological inspection (contractile activity), quantitative mRNA analysis and cardiac-specific expression of green fluorescent protein (GFP), used as a quantitative reporter. The data from the different endpoints have been subjected to a statistical analysis, and a preliminary prediction model is proposed. The results demonstrate that genetically-engineered ES cells could provide a valuable tool for estimating the developmental cardiotoxic potential of compounds in vitro and form the basis for automated analysis in a high-throughput system.

Animals↗

PubMed1999

ECVAM and the Promotion of International Co-operation in the Development, Validation and Acceptance of Replacement Alternative Test Methods.

The European Centre for the Validation of Alternative Methods (ECVAM) was established by the European Commission in 1991, to co-ordinate the validation of alternative methods at the European Union level, to establish a database on alternative methods, and to promote dialogue among all the interested parties, in order to secure the international recognition and acceptance of validated alternative test methods. All ECVAM activities, including workshops, task forces, in-house laboratory studies, and contracted external pre-validation and validation studies, involve international co-operation. Of particular importance has been the role played by ECVAM, notably in partnership with ZEBET, in establishing the principles of test development, validation and acceptance, defining the practical procedures necessary to optimise the progress of new tests toward acceptance, and in successfully validating the 3T3 NRU PT test for phototoxic potential. It is vital that international co-operation goes beyond mere discussion and leads to definite collaborative projects, which lead, in turn, to genuine achievements.

Journal Article↗

PubMed1999

The Funding of Research on the Three Rs in the EU.

In a number of European countries, notably Germany, The Netherlands, Sweden and the UK, there has been a significant commitment to research designed to achieve one or more of the Three Rs. This work has been funded by industry, by government, and by the animal welfare movement. The cosmetic industry, ZEBET in Germany and the Dutch Platform in The Netherlands, and FRAME in the UK, deserve particular mention. The European Commission also plays a major role, in two main ways. Firstly, research is supported via DGXII, particularly through programmes such as BRIDGE, BIOTECH and BIOMED in the Third and Fourth Framework Programmes (1991-1998). In the Fifth Framework Programme (1999-2002), major support for international collaborative studies on the development of replacement alternative test methods will be provided as parts of programmes concerned with the Cell Factory (novel in vitro testing as alternatives to animal testing) and Environment and Health (improvement of predictive toxicity testing, with emphasis on in vitro test systems and alternative screening and testing protocols). The second kind of funding is by competitive contracts for specific studies required by various Services of the Commission, including, for example, pre-validation and validation studies conducted for ECVAM.

Journal Article↗

PubMed1998

13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies and conceptual issues.

Substantial world-wide resources are being committed to develop improved toxicological testing methods that will contribute to better protection of human health and the environment. The development of new methods is intrinsically driven by new knowledge emanating from fundamental research in toxicology, carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of other disciplines. Critical evaluations and strong scientific consensus are essential to facilitate adoption of alternative methods for use in the safety assessment of drugs, chemicals, and other environmental factors. Recommendations to hasten the development of new alternative methods included increasing emphasis on the development of mechanism-based methods, increasing fundamental toxicological research, increasing training on the use of alternative methods, integrating accepted alternative methods into toxicity assessment, internationally harmonizating chemical toxicity classification schemes, and increasing international cooperation to develop, validate, and gain acceptance of alternative methods.

Animal Testing Alternatives↗

PubMed1998

Mechanistic approaches and the development of alternative toxicity test methods.

A mechanism can be defined as an explanation of an observed phenomenon that explains the processes underlying the phenomenon in terms of events at lower levels of organization. A prerequisite for new, more mechanistic, approaches, which would use in vitro systems rather than conventional animal analogy models, is a strengthening of the underlying scientific basis of toxicity testing. This will require greater recognition of the differences between fidelity and discrimination models and between analogy and correlation models. The development of high-fidelity, high-discrimination tests with a sound mechanistic basis will also require greater appreciation of the interdependence of all the components of test systems and the development of new alternative (i.e., nonanimal) testing strategies that can provide the specific knowledge needed for making relevant and reliable predictions about the potential effects of chemicals and products in human beings. The optimal use of this new knowledge will require fundamental changes to current practices in risk assessment.

Animal Testing Alternatives↗

PubMed1997

Perspectives on alternatives to the eye irritation test: industry, public interest, government.

Government mandates are requiring serious consideration of alternatives to animal testing. For eye irritation testing, many non-whole animal alternatives exist that now need to be assessed as to their validity in replacing the animal model. The best promise for identifying useful alternatives comes from using both statistical and biological factors to evaluate results from formal validation studies. Industry submissions of side-by-side animal and alternative test results are also important. Empirical test results should be scrutinized first; mechanistic studies should follow, as needed. Co-operation is required by all parties to develop internationally harmonized test protocols and hazard classification systems.

Animal Testing Alternatives↗

PubMed1996

The three Rs of Russell & Burch and the testing of biological products.

The principles of humane animal experimentation proposed by Russell & Burch (1959), namely, replacement, reduction, and refinement, are now commonly known as the Three Rs. These principles are clearly embodied in Article 7 of Directive 86/609/EEC. It is instructive, therefore, to consider the priority currently attached to compliance with these principles and to the Directive in the development and control of biological products. Specific comments are made on the need for the application of the Three Rs in relation to the testing of human diphtheria and tetanus vaccines, human pertussis vaccine, inactivated veterinary Gumboro vaccine, veterinary Newcastle disease vaccine, veterinary clostridial vaccines and botulinum toxin. We pose three questions: a. Are the minimum numbers of animals already being used in this area? b. Is any unnecessary pain, suffering, distress or lasting harm being inflicted on the animals used? and c. What could and should be done about any shortcomings in current practice? Finally, the role of ECVAM in the promotion of the Three Rs within the European Union will be reviewed.

Animal Testing Alternatives↗

PubMed1995