Ethical review of regulatory toxicology guidelines involving experiments on animals: the example of endocrine disrupters.
The safety assessment of new chemicals (including medicines, pesticides, food additives, and industrial chemicals) relies on the results of animal experiments. Because the safety of those exposed to these products and the welfare of the experimental animals used are considered critically important, both testing requirements and the welfare of experimental animals are controlled by law. In the U.K., projects that propose to use animals for experimental purposes, including for the testing of chemicals, have been controlled by law for over a century, with the most recent legislation (Animals [Scientific Procedures] Act of 1986) requiring a cost/benefit assessment before it may proceed. New regulations introduced in 1998 will require an ethical review process for all projects from April 1999. Such ethical review will have to take account of the toxicity testing methods and schemes that are required by the legislation aimed at protecting human health. Neither national nor international proposals for toxicity testing methods and schemes are generally subjected to ethical review from the point of protecting animal welfare. The international nature of the chemical and pharmaceutical industry means that testing requirements from one of the major national regulatory agencies (USA, EU, or Japan) or the international organizations (Organization for Economic Co-operation and Development [OECD]or the International Conference on Harmonization [ICH]) have an impact on the testing carried out by industrial organizations in all countries. The recent proposals for screening and testing chemicals to identify endocrine disrupters (ED) from the Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) of the U.S. Environmental Protection Agency (EPA) are used as an example of the interaction between regulatory proposals and animal welfare issues. The current proposals are the most extravagant in the use of animals. Between 0.6 and 1.2 million animals would be required for each 1000 chemicals tested. The EPA, before incorporating them into regulation, is subjecting the recommendations to further review. This will undoubtedly moderate the number of animals actually used from the worst-case calculation. The variables that have the greatest impact on the number of animals required for testing are the prevalence of ED chemicals in the chemicals to be tested, and the sensitivity and specificity of the testing methods. The modeling demonstrates, for example, that increasing the prevalence from 10 to 50% reduces the number of animals used to detect one ED from 10,000 to 2700. Knowledge of the prevalence of EDs in the chemicals to be tested would allow rational selection of tier one screening based on the sensitivity and specificity of the screening tests. The EDSTAC proposals are difficult to justify from an ethical perspective, as equally effective detection rates may be achieved with fewer animals. National and international regulatory testing proposals should be subjected to formal independent ethical review before they are finalized, with a view to improving animal welfare. (+info)
A reply to Joseph Bernstein.
Dr. Bernstein suggests that anti-vivisectionists should be able to fill in a directive requesting that they receive no medical treatment developed through work on animals. It is replied that this would only be reasonable if research not using animals had long been funded as adequately and its results were currently available. (+info)
A chair on alternatives?
An overview is given on the legal framework in Europe for the use of experimental animals set by EU (European Union) Directive 86/609/EEC and on the activities of EU member states to implement this directive in the field of regulatory testing in animals. The significant decrease in the number of experimental animals in Germany during the past decade is described with particular reference to the recent increase that is due to transgenic animal models. From the regulatory and the animal welfare perspective the international harmonisation of test guidelines and the mutual acceptance of data are the way forward for chemical safety testing. The recent White Paper of the EU Commission for the future chemicals policy calls for an immediate increase in the number of validated in vitro toxicity tests to be accepted for regulatory purposes in the EU. In addition, deficits of properly educating young scientists in Germany in conducting animal experiments and implementing the 3-Rs concept of Russel and Burch are described. It is therefore, quite urgent to establish new chairs on animals and alternatives at universities in Europe. They should focus on both education young students of the biomedical sciences in the humane use of laboratory animals according to the 3-Rs concept and on developing new toxicity tests to be validated for regulatory purposes under the new EU chemicals policy by the established validation centres in Europe. (+info)
Replacement, reduction and refinement.
In 1959, William Russell and Rex Burch published "The Principles of Humane Experimental Technique". They proposed that if animals were to be used in experiments, every effort should be made to Replace them with non-sentient alternatives, to Reduce to a minimum the number of animals used, and to Refine experiments which used animals so that they caused the minimum pain and distress. These guiding principles, the "3 Rs" of animal research, were initially given little attention. Gradually, however, they have become established as essential considerations when animals are used in research. They have influenced new legislation aimed at controlling the use of experimental animals, and in the United Kingdom they have become formally incorporated into the Animal (Scientific) Procedures Act. The three principles, of Replacement, Reduction and Refinement, have also proven to be an area of common ground for research workers who use animals, and those who oppose their use. Scientists, who accept the need to use animals in some experiments, would also agree that it would be preferable not to use animals. If animals were to be used, as few as possible should be used and they should experience a minimum of pain or distress. Many of those who oppose animal experimentation, would also agree that until animal experimentation is stopped, Russell and Burch's 3Rs provide a means to improve animal welfare. It has also been recognised that adoption of the 3Rs can improve the quality of science. Appropriately designed experiments that minimise variation, provide standardised optimum conditions of animals care and minimise unnecessary stress or pain, often yield better more reliable data. Despite the progress made as a result of attention to these principles, several major problems have been identified. When replacing animals with alternative methods, it has often proven difficult to formally validate the alternative. This has proven a particular problem in regulatory toxicology, especially when combined with the labyrinthine processes of the various regulatory authorities. The principle of Reduction would appear less contentious, but its application has highlighted the difficulties of providing appropriate expert statistical advice, especially in academic research facilities. In some instances, concern to implement Reduction strategies can result in the use of too few animals, which leads to inconclusive results, and wasteful experiments. It is in the area of Refinement, however, that major problems have arisen. Much of our judgement of what represents Refinement is based on little more than common sense. We make assumptions about animals and their feelings that often have little scientific basis. In many instances we may be correct, but these assumptions may become incorporated into institutional or national policies, without any attempt to verify them. To give an example - it is reasonable to assume that animals will experience pain after a surgical procedure, so pain-relieving drugs should be given to prevent this. We have some idea of the appropriate dose of analgesics for most animals, but effective pain relief requires that dose given is adjusted to meet the requirements of the individual animal. Requiring every animal to have the same dose of the same drug after any surgical procedure is not the best way of dealing with post-operative pain. Discussion of these problems should not detract from the very significant progress that has been made in the 40 or so years since Russell and Burch set out their guiding principles. What is needed now is greater academic focus on this area, not only to work on new methods of implementing the 3Rs, but also to disseminate current "Best Practice", and to revise this advice as further progress is made. (+info)
Science and society: different bioethical approaches towards animal experimentation.
The use of live animals for experiments plays an important role in many forms of research. This gives rise to an ethical dilemma. On the one hand, most of the animals used are sentient beings who may be harmed by the experiments. The research, on the other hand, may be vital for preventing, curing or alleviating human diseases. There is no consensus on how to tackle this dilemma. One extreme is the view taken by adherents of the so-called animal rights view. According to this view, we are never justified in harming animals for human purposes - however vital these purposes may be. The other extreme is the ruthless view, according to which animals are there to be used at our discretion. However, most people have a view situated somewhere between these two extremes. It is accepted that animals may be used for research - contrary to the animal rights view. However, contrary to the ruthless view, that is only accepted under certain conditions. The aim of this presentation is to present different ethical views which may serve as a foundation for specifying the circumstances under which it is acceptable to use animals for research. Three views serving this role are contractarianism, utilitarianism and a deontological approach. According to contractarianism, the key ethical issue is concern for the sentiments of other human beings in society, on whose co-operation those responsible for research depend. Thus it is acceptable to use animals as long as most people can see the point of the experiment and are not offended by the way it is done. According to utilitarianism, the key ethical issue is about the consequences for humans and animals. Thus it is justified to use animals for research if enough good comes out of it in terms of preventing suffering and creating happiness, and if there is no better alternative. In the deontological approach the prima facie duty of beneficence towards human beings has to be weighed against the prima facie duties not to harm animals and to respect their integrity. By weighing these prima facie duties, the moral problem of animal experimentation exists in finding which duty actually has to be considered as the decisive duty. It will be argued that these three views, even though they will all justify animal experimentation to some extent, will do so in practice under different conditions. Many current conflicts regarding the use of animals for research may be better understood in light of the conflict between the three bioethical perspectives provided by these views. (+info)
Fears grow about animal rights activists.
The British government has blocked entry to a key American animal rights campaigner but there are growing concerns about local developments. (+info)
Ahimsa and alternatives -- the concept of the 4th R. The CPCSEA in India.
The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) in India is one of a kind in the world. It is a statutory body of the government of India formed by an act of the Indian parliament. This body consists of nominated members and representatives from national regulatory agencies, Ministry of Health and Family Welfare, Ministry of Environment and Forests, national academic and research councils, premier research institutes, eminent scientists and animal welfare organisations. The CPCSEA draws its powers from the Prevention of Cruelty to Animals (PCA) Act of 1960 which states that the duty of the committee is "to take all such measures as may be necessary to ensure that animals are not subject to unnecessary pain or suffering before, during or after the performance of experiments on them". With the power to promulgate its own laws to ensure the humane and ethical use of animals in research and education, the CPCSEA in 1998 notified in the gazette of India the "Breeding of and Experiments on Animals (Control and Supervision) Rules 1998". The CPCSEA is unique in that the law in itself has enabled the creation of a common platform of discussion for scientists and animal activists for humane and progressive solutions for the use of animals in experimentation. In a country that is caught in a paradox of violence and rich cultural and religious traditions, India still draws a lot of its power from the concept of "Ahimsa" (the philosophy of non-violence). This concept is also pertinent to the use of animals in laboratories. Unethical, inhumane and unscientific practices, and ignorance of the use of alternatives were the way of science until 1999 when CPCSEA became functional. For four years CPCSEA has waged a battle, rescued thousands of animals from laboratories, fought legal battles to victory, enforced for the first time in the country good laboratory practice, designed guidelines for the use of animals in the production of immunobiologicals, introduced the credo of 3R principles, trained and taught scientific personnel the credibility of humane science and most importantly brought forward the concept of the fourth R, "rehabilitation" of used laboratory animals. Today CPCSEA has made it a national policy that personnel using experimental animals have a moral responsibility towards these animals after their use. Costs of after-care/rehabilitation of animals post experimentation are to be a part of research costs and should be scaled in positive correlation with the level of sentience of the animals. This paper is about the Indian law on animal experimentation and the success story of the CPCSEA in India in inculcating the credo of 4Rs -- Replacement, Reduction, Refinement, and Rehabilitation of animals used in experimentation. (+info)
Laboratory animals and the art of empathy.
Consistency is the hallmark of a coherent ethical philosophy. When considering the morality of particular behaviour, one should look to identify comparable situations and test one's approach to the former against one's approach to the latter. The obvious comparator for animal experiments is non-consensual experiments on people. In both cases, suffering and perhaps death is knowingly caused to the victim, the intended beneficiary is someone else, and the victim does not consent. Animals suffer just as people do. As we condemn non-consensual experiments on people, we should, if we are to be consistent, condemn non-consensual experiments on animals. The alleged differences between the two practices often put forward do not stand up to scrutiny. The best guide to ethical behaviour is empathy--putting oneself in the potential victim's shoes. Again to be consistent, we should empathise with all who may be adversely affected by our behaviour. By this yardstick, too, animal experiments fail the ethical test. (+info)