bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines for Humane Education: Alternatives to the Use of Animals in Teaching and Training
Authors: Smith Adrian J.L. , Smith Karina
Published: April 2019

There are few areas of animal use that are so emotive as that of their use in education. The physical presence of an animal (whether alive or dead) is a dramatic event for most students, and the effects it has will depend heavily on their previous experience with that species, their moral values and the perceived necessity of the practical. Much of the literature on this subject is highly emotive and based on relatively little data. This paper attempts to clarify the issues raised, presents an overview of the alternatives available with their strengths and weaknesses, and finally offers guidelines for humane education that take into consideration both the practical issues and the feelings of all those involved.
The Establishment of the UK Human Tissue Bank
Authors: Orr Samantha , Trafford Jacki
Published: April 2019

The UK Human Tissue Bank (UKHTB) was established in 1998, to provide biomedical researchers with an effective, transparent and ethical supply of human tissues. The UKHTB collects and processes non-transplantable human tissue from cadaveric brain stem dead donors and surgical tissues surplus to diagnostic requirements, and distributes to researchers working in UK universities, medical institutions and the pharmaceutical industry. The UKHTB has gained approval from UK National Health Service Ethical Committees for the receipt of human tissues and transfers donated tissues to researchers with allied approval, who additionally agree to the scrutiny of the end-use of tissue by the UKHTB. All donations are made with the informed consent of the donor family or patient. In this way, all donations are traced from source to end-use. The UKHTB operates under a not-for-profit policy and employs a method of cost recovery to recoup processing, staff and transport costs; the tissue itself is not subject to a charge. We are confident that improved access to human tissue models results in more relevant results being ultimately available for clinical practice.
Proliferation of Epidermal Growth Factor-stimulated Hepatocytes in a Hormonally Defined Serum-free Medium
Authors: Papeleu Peggy , Loyer Pascal , Vanhaecke Tamara , Henkens Tom , Elaut Greetje , Guguen-Guillouzo Christiane , Rogiers Vera
Published: April 2019

The present study shows that adult rat hepatocytes in primary culture, which normally exhibit a restricted capacity to proliferate, can proceed through the cell cycle when cultured in a mixture of minimal essential medium (MEM) and Medium 199 (MEM–M199; 3:1, v/v), containing epidermal growth factor (EGF; 50ng/ml), low glucose (0.75g/l) and low levels of inorganic salts, amino acids and vitamins. Under these conditions, hepatocytes flatten and cell extensions appear. In contrast, Dulbecco's modified Eagle's medium (DMEM) containing high glucose (4.5g/l) levels enriched with inorganic salts, amino acids and vitamins favours maintenance of differentiated functional hepatocyte capacities (albumin secretion), but does not allow proliferation or cell spreading. Cultivation of hepatocytes in MEM–M199 (3:1, v/v) results in the onset of DNA synthesis at 48 hours of culture and a concomitant induction of cyclin D1 protein. Under these conditions, cells successively progress through the mitogen-dependent restriction point in mid-late G1 phase, G1/S transition and S phase, as evidenced by Western blot analysis of the markers cyclins E and A and cyclin dependent kinase (CDK)2 and CDK1, respectively. Progression through the cell cycle is accompanied by a decrease in albumin secretion, indicating a decline in differentiated capacities. This study demonstrates that hepatocytes cultured in a mixture of MEM–M199 (3:1) provide a useful in vitro model for studying the regulation of hepatocyte proliferation.
Search Filters, a New Tool in the Search for Alternatives: Locating Mouse Strains as Disease Models
Authors: Wood Mary W. , Hart Lynette A.
Published: April 2019

By manipulating available databases and resources and making use of existing technology, a new tool can be used in the alternatives search. The Clinical Queries search filter, available in PubMed, can locate precise information on published studies of specific mouse strains and disease processes. Though commonly used, mice are highly divergent in their strain characteristics. Monitoring previously published work by strain allows scientists to select appropriate strains as disease models, while avoiding inappropriate strains or repetition of earlier studies. The Jackson Laboratory provides detailed information on mouse strains of particular interest. At the University of California (UC), federal regulations imposed by the US Government are implemented at the nine campuses, requiring UC scientists to consider alternatives by performing literature searches. This blanket requirement can be perceived as an obstacle and result in searches that, though compliant with regulations, are not productive. By crafting user-friendly and relevant searching tools, the UC Center for Animal Alternatives (UCCAA) makes searching both less onerous and more productive, thereby increasing the chances that alternatives will be integrated into the protocol. Through the use of these new search filters, as well as stored searches, species-specific resources, and readily available websites, The UCCAA provides user-friendly access to current information: www.vetmed.ucdavis.edu/animal_alternatives/main.htm . Website use statistics continue to increase, indicating that this immediate retrieval of relevant information is meeting our researchers’ needs.
Experimental Design: Computer Simulation for Improving the Precision of an Experiment
Authors: van Wilgenburg Henk , van Schaick Zillesen Piet G. , Krulichova Iva
Published: April 2019

An interactive computer-assisted learning program, ExpDesign, that has been developed for simulating animal experiments, is introduced. The program guides students through the steps for designing animal experiments and estimating optimal sample sizes. Principles are introduced for controlling variation, establishing the experimental unit, selecting randomised block and factorial experimental designs, and applying the appropriate statistical analysis. Sample Power is a supporting tool that visualises the process of estimating the sample size. The aim of developing the ExpDesign program has been to make biomedical research workers more familiar with some basic principles of experimental design and statistics and to facilitate discussions with statisticians.
The Principles of Validation and the ECVAM Validation Process
Authors: Worth Andrew P. , Balls Michael
Published: April 2019

The validation of a test method is the process by which the relevance and reliability of the method are assessed for a particular purpose. It is an essential stage in the evolution of the method from its development to its acceptance and application for regulatory purposes. The principles according to which alternative tests should be validated have been agreed upon at an international level, although the actual process by which the validation process is conducted varies between different validation authorities. This paper summarises the principles of alternative test development and validation and describes how the principles have been applied to the validation of in vitro tests by the European Centre for the Validation of Alternative Methods (ECVAM).
The Third FRAME Toxicity Committee: Working toward Greater Implementation of Alternatives in Toxicity Testing
Authors: Combes Robert D. , Balls Michael , Bansil Lee , Barratt Martin , Bell David , Botham Philip , Broadhead Caren , Clothier Richard , George Elizabeth , Fentem Julia , Jackson Michael , Indans Ian , Loizou George , Navaratnam Vyra , Pentreath Victor , Phillips Barry , Stemplewski Henry , Stewart Jane
Published: April 2019

FRAME (the Fund for the Replacement of Animals in Medical Experiments; http://www.frame.org.uk ) is a scientific charity, which has, for over 30 years, been advocating and conducting its own research on the application of the Three Rs ( reduction, refinement and replacement) to animal experimentation. FRAME develops and validates scientifically based replacement alternative methods to facilitate their acceptance by scientists and regulators. As part of these activities, FRAME established a FRAME Toxicity Committee in 1979, and a report of its work was published in 1982, and discussed in the proceedings of a subsequent meeting, published in 1983. A Second Toxicity Committee formed in 1988, reported its work in 1990, which was discussed in the proceedings of a subsequent conference, published in 1991. The work of these committees was extremely successful and influential in laying the foundation for later activities in alternatives research. A Third FRAME Toxicity Committee was formed in 1999, since much progress had been achieved in the previous decade, especially with regard to the successful validation of several non-animal replacement methods and the start of their regulatory acceptance. Moreover, some new test methods are on the point of being validated, and many new techniques and discoveries are impacting on toxicity testing. Also, interest in reduction and refinement in toxicology has increased. However, there is considerable scope and need for the further implementation of the Three Rs in toxicity testing, especially due to recent plans for the large-scale testing of high-production volume, hormonally-active and existing chemicals, and the increasing use of transgenic animal models. The new committee comprises 18 experts from industry, academia, animal welfare, legislative and regulatory bodies, with one observer from the UK Government Home Office. The main objective is to review progress made in the application of the Three Rs in the development and safety evaluation of medicines, biologicals, cosmetics, agrochemicals and other products, as well as industrial chemicals, and to make recommendations as a basis for further sensible progress according to sound scientific and ethical criteria. The main committee is to be augmented by several working parties that will focus on specific scientific issues: 1) targeted risk assessment versus hazard identification; 2) data sharing; 3) endocrine disruption; and 4) carcinogenicity testing. The Committee is also to publish a status report on the current situation regarding alternatives in toxicity testing, based on the recommendations of the Second Toxicity Committee, and will organise a conference to discuss its overall conclusions and recommendations.
Considering the Test Performance for Three Class Data Using Linear Discriminant Analysis: A Case Study
Authors: Genschow Elke , Seiler Andrea , Spielmann Horst
Published: April 2019

The results of a European Centre for the Validation of Alternative Methods validation study on the embryonic stem (ES) cell test were used as an example for the test performance for “three-class” data using linear discriminant analysis (LDA). Applying LDA, a biostatistical prediction model was developed to assign test chemicals to three classes of embryotoxicity. Three endpoint values were identified to classify the embryotoxic potential of chemicals: a) the inhibition of differentiation of ES cells into cardiomyocytes (ID50), b) the decrease of viability of adult 3T3 cells (IC503T3), and c) the decrease of viability of ES cells (IC50D3) in an MTT cytotoxicity test. It could be demonstrated that an objective statistical method was required in order to minimise the probability of misclassification. The management team of the validation study defined performance criteria, taking into consideration the hit rate for three classes obtained just by chance. An additional purpose of the study reported here was to calculate a hypothetical prevalence and evaluate its influence on the classification results.
Quality Assurance for In Vitro Alternative Test Methods: Quality Control Issues in Test Kit Production
Authors: Rispin Amy , Harbell John W. , Klausner Mitchell , Jordan Foster T. , Coecke Sandra , Gupta Kailash , Stitzel Katherine
Published: April 2019

In vitro toxicology methods are being adopted by regulatory agencies worldwide. Many of these methods have been validated by using proprietary materials, often in the form of test kits. Guidelines for the use of Good Laboratory Practice methods for in vitro methods have been proposed. However, users of the data from these methods also need to be reassured that the proprietary materials and the test kits will provide consistent, good quality data over time, not just during the validation process. This paper presents an overview of the methods currently used by representatives of kit manufacturers and contract testing laboratories to ensure that the results from methods that utilise test kits are reproducible over time and across different types of test materials. This information will be valuable as a basis for future discussion on the need for formalised oversight of the quality of these materials.
Is the Use of Animals in Biomedical Research Still Necessary in 2002? Unfortunately, “Yes”
Authors: Festing Michael F.W.
Published: April 2019

The use of laboratory animals in the year 2002 is essential both to maintain human health and to develop new treatments for the many diseases that still plague humans. The suggestion by Greek and Greek in Sacred Cows and Golden Geese in 2000, that animal experiments are invalid because animals are different from humans, shows clearly that they do not understand the philosophical basis for the use of models in science and every day life. Models only need to resemble the thing being modelled (the target) in a few key respects. A map of Brooklyn Botanic Garden is a useful model, but it differs from the garden in many respects. There are many examples where studies on animals and in vitro alternatives result in accurate predictions of human responses even though the models differ from humans in other ways. In the drug development model, validation is done in clinical trials. Models are also used in the discovery of fundamental processes shared by some, or all, living organisms. The laws of genetics were first discovered by using garden peas, but they are equally applicable to humans. It is because of the ethical, rather than scientific, objections to the use of animals that all scientists are urged to find alternatives according to the principles of reduction, refinement and replacement, laid down by Russell and Burch in 1959.
Are Animals Necessary in Biological Education?
Authors: Jukes Nick
Published: April 2019

Ensuring the most ethical and effective ways of meeting teaching objectives requires good curricular design. Such design should be informed by knowledge of the available learning tools and approaches, and by reviews and studies that investigate their pedagogical efficacy. Alternatives have been shown to meet teaching objectives as least as well as conventional animal use, and they do not share the “hidden curriculum” of animal practicals that can teach disrespect for life and hinder the development of critical thinking skills. Most alternatives have been developed by teachers for their pedagogical and scientific benefits, and their implementation can bring cutting-edge technology to the process of learning. For the minority of students who genuinely need hands-on experience with animals, the use of ethically sourced animal cadavers and tissue, and clinical work with animal patients, can offer valuable learning opportunities. No animal needs to be killed or harmed within biological education.
Evaluation of Some In Vitro Tests to Reduce and Replace the Sub-acute Animal Toxicity Studies
Authors: Chhabra Rajendra S. , Ress Nancy B. , Harbell John W. , Curren Rodger D.
Published: April 2019

The toxicologic and carcinogenic potential of chemicals is usually determined through a sequence of acute, sub-acute (14-day), sub-chronic (90-day) and chronic (two-year) studies in rats and mice of both sexes. The US National Toxicology Program (NTP) does not conduct acute toxicity studies. Dose levels for 14-day toxicity studies are typically estimated from information in the literature, if available. The toxicology information obtained from 14-day studies is used in the selection of doses for 90-day studies. The protocol for 14-day studies consists of five doses and control groups and five animals per group of each sex and species, resulting in the use of 120 animals per study. At present, in addition to refining the current testing protocols, the NTP is evaluating the potential for in vitro test methods to partially or completely avoid the need for 14-day toxicity studies, especially for chemicals where the dermal route of exposure is used. The in vitro assays used were the EpiDerm™ bioassay to estimate dermal irritation, the neutral red uptake (NRU) bioassay to estimate systemic toxicity and the primary rat hepatocyte cytotoxicity (PRHC) assay to estimate hepatotoxicity. The purpose of using these assays was to assess their potential for predicting relative in vivo toxicity and to support dose selection decisions for 90-day studies. In general, based on these limited number of studies, the EpiDerm and NRU tests were predictive of the responses observed in in vivo studies. However, a larger comparative database is needed to derive definitive conclusions regarding the value of in vitro tests in the prediction of in vivo effects.
Social Housing of Large Primates: Methodology for Refinement of Husbandry and Management
Authors: Wolfensohn Sarah
Published: April 2019

Improvement of primate facilities is potentially costly, and is constrained by health and safety considerations and by limited experience in smaller units. During the last decade, most units have progressed from two-tier, single housing on grid floors, but there are still opportunities for refinements to reduce contingent suffering. The methodology of housing rhesus monkeys loose in rooms without cages has been documented in a video presentation. The animals have defined health status, but routine room maintenance and animal handling encourage close staff contact, generating health and safety concerns. The management changes have resulted in less aggressive, more-cooperative animals that are less stressed by capture. There are more natural behaviours, together with decreased animal and staff stress, resulting in better experimental models. The cages remain cleaner, releasing staff to spend more time on positive reinforcement training. There is better use of available space, and experimental immunology studies have been included within the breeding colony. The project has demonstrated a way of providing a management system that results in major benefits to animal welfare, staff morale and to the quality of the scientific studies undertaken. The methodology is now being used in an experimental unit housing animals for neuroscience. Continuing challenges include some social unrest within groups, managing animal health and maintaining high levels of personnel safety.
The Environmental Enrichment Committee
Authors: Stewart Kay L.
Published: April 2019

Both the US Guide for the Care and Use of Laboratory Animals and the Canadian Council on Animal Care Guide to the Care and Use of Experimental Animals specify that suitable enrichment and social interaction with con-specifics should be considered when planning adequate housing for all laboratory animal species. In response to this dictum, the University of Notre Dame established an Environmental Enrichment Committee to develop, implement and assess an overall enrichment programme that encompasses all species housed at the Freimann Life Science Center. Although many enrichment strategies had been used prior to the formation of the committee, having the facility director formally authorize a committee gave the members credibility with the Principle Investigators, resources for programme development and time allotments for meetings and observations. The committee members began their assignment by defining the committee goals and responsibilities. Six categories for the enrichment strategies were established: social interaction, burrowing opportunities, perches and ramps, foraging opportunities, gnawing opportunities and food treats. A programme was developed to encompass the use of techniques within these categories with the animals that would benefit from them. Our experience is that the Environmental Enrichment Committee is an effective vehicle for the development and implementation of enrichment strategies.
The Use of Animals for Research on Animal Diseases: Its Impact on the Harm–Benefit Analysis
Authors: Rickard Michael D.
Published: April 2019

The use of animals in scientific experiments is sometimes controversial. Usually, the debate focuses on the advantages or disadvantages of using animals in biomedical research or for testing products for safety or efficacy in humans. This has been the case in the previous World Congresses on Alternatives and Animal Use in the Life Sciences. Such studies can be subjected to a harm–benefit analysis that attempts to assess the expected benefits of the research to be done in relation to the harm done to the experimental animals. This paper suggests that studies carried out in the target species offer a higher level of fidelity and discrimination (confidence in the proper expression of the disease and greater ability to detect the impacts of any treatments under investigation) than do experiments carried out in animal models of a different species. A number of examples are given to show the benefits that have accrued to the welfare of domesticated animals through research on the diseases from which they suffer. These examples suggest that there will be an ongoing need to use animals in research to develop methods for the control or eradication of newly emergent diseases.
Overview and Analysis of Animal Use in North America
Authors: Gauthier Clément
Published: April 2019

The Canadian Council on Animal Care (CCAC) publishes data on over 25 species of animals used in science, and the US Department of Agriculture publishes data on six of those species. Between 1980 and 1999, the reduction in animal use was found to be correlated between Canada and the USA for dogs (r = 0.944, p < 0.001), cats (r = 0.839, p < 0.001), rabbits (r = 0.852, p < 0.001) and hamsters (r = 0.716, p < 0.01), with no significant correlation found for non-human primates and guinea-pigs. On the basis of the four species where correlation between the two countries was found for reduction in use, the mean ratio of the number of animals used in the USA compared to the number used in Canada was 17.0 ± 7.5. The CCAC data for these six US-regulated species were used in an analysis of regression with multiple predictors to test whether they could be used to predict the total number of animals used. No significant correlation was found. However, using the same analysis, rats, mice, fish and birds were found to be highly correlated with the total number of animals used (r2 = 0.9835, p < 0.005). The regression equation developed by using Canadian data was validated using UK animal use numbers. An almost perfect fit between the estimated values provided the evidence that total animal use in Canada and the UK decreased at about the same pace during the 1990s. Animal use data can be a useful tool to monitor the implementation of reduction measures. However, their use for the monitoring of refinement measures requires care and analysis. For example, the sustained downward trend in the number of experiments causing severe pain in unanaesthetised animals (category of invasiveness [CI] E) observed in Canada and the USA between 1996 and 1999 is indicative of effective refinement, but it would be misleading to interpret the increase in the number of animals used in Canada under CI D in 1997 as an indication of greater pain and distress. In fact, the larger number of animals in CI D resulted at least in part from the implementation of new CCAC guidelines designed to ensure better monitoring of transgenic animal care and use.
Recent Trends in the Number of Laboratory Animals Used in Japan
Authors: Matsuda Yukihisa
Published: April 2019

Surveys on the numbers of laboratory animals used in Japan have been conducted by both the Japanese Association for Laboratory Animal Science (JALAS) and the Japanese Association for Laboratory Animals in National Universities (JALAN). According to the JALAS, in 1998, 5,626,116 animals were used in experiments. Rodents, such as mice and rats, made up 87% of that total, while the total number of dogs, cats and monkeys used was less than 1%. The JALAS reported that the total number of animals used in experiments in 1990 was 8,737,770, a peak of 10,013,584 was reached in 1995, and thereafter the number gradually decreased to 5,626,116 in 1998. During this period, the number of all the species used, except non-human primates and farm animals, decreased. The number of dogs and cats used decreased by over 65%. This decrease was attributed to the activities of animal welfare groups. On the other hand, the JALAN reported that the total number of animals used in experiments doubled from 1991 to 1999. The increase could be attributed to use of genetically modified mice, such as transgenic and knockout mice. Noting problems with the methods used, we concluded that the number of the laboratory animals used in Japan, other than rodents, has been gradually decreasing since 1991.
The Great Ape Project: Legislating for the Control of the Use of Non-human Hominids in Research, Testing and Teaching — Animal Welfare Act 1999 (New Zealand)
Authors: Wells Neil
Published: April 2019

The Animal Welfare Act 1999 (New Zealand), which commenced on January 1 2000, provides that the use of non-human hominids in research, testing or teaching is not permitted unless the Director-General of Agriculture approves the use, and then, only if the use is in the interests of the non-human hominid itself or its species. The Animal Welfare Act 1999 originated with two parliamentary bills. The first, a private member's bill in the name of Pete Hodgson MP, was tabled in 1997, and the second, a Government measure, was tabled a year later. Neither bill made any reference to non-human hominids. The Great Ape Project made submissions that non-human hominids be afforded similar rights to humans, i.e. not to be deprived of life, not to be subjected to torture or cruel treatment and not to be subjected to medical or scientific experimentation. Proponents and opponents of the measure argued for and against the tenet of introducing “rights” issues into what was essentially “welfare” legislation. These arguments are analysed, and the legislative process that enabled this modification is examined.
The New EU Chemicals Policy: Challenges and Chances for Animal-free Test Methods
Authors: Sauer Ursula G.
Published: April 2019

As a first step toward preparing new chemicals legislation, in February 2001, the European Commission adopted a White Paper on a Strategy for a Future Chemicals Policy. Its main goals are to better protect humans and the environment from unknown risks through chemicals. The “promotion of non-animal testing” is one of the key elements of the proposed strategy. For low production volume chemicals, only data from in vitro tests are to be requested. The data requirements for higher production volume chemicals will be designed flexibly, so that only data relevant for the respective chemical are collected. From the point of view of animal welfare risk management, strategies should be defined before test batteries are put together. The test catalogues currently listed in the Dangerous Substances Directive, Council Directive 67/548/EEC, are to be replaced by flexible, tiered-testing strategies, and concrete waiving strategies are to be designed. The avoidance of duplicate testing should become mandatory. In order to fill prevailing knowledge gaps, the funding of alternative method research should be given priority by the EU Commission, and thus should receive a concrete budget. It should have been formulated as a key action in the European Sixth Research Framework Programme.
Humane Regulatory Testing: The United Kingdom Experience
Authors: Richmond Jon D.
Published: April 2019

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.
TestSmart and Toxic Ignorance
Authors: Green Sidney , Goldberg Alan M.
Published: April 2019

There are a number of national and international efforts designed to screen chemicals for toxicity. Although the emphasis in terms of the specific chemicals is different, e.g. endocrine disruptors, children's health, High Production Volume (HPV), the European Registration, Evaluation, Authorization of Chemicals (REACH) programme, the purpose is the same. Each is intended to evaluate the potential toxicity of chemicals to humans and, in some cases, to the environment. How best can these tasks be accomplished? The first need is to provide a realistic prioritisation of which chemicals need to be evaluated. Once identified, a defined decision-tree approach with an emphasis on short-term in vitro assays and new genomic technologies offers the greatest promise. The more practical matter of screening the chemicals would be by using a tiered decision-tree approach. Common features of the approach would be the use of three tiers. The first tier would be a screening/prioritisation tier, the second would provide an initial characterisation of toxicity, and the third would discern mode of action/biological activity. The intent of this approach is to provide a concept that will allow decisions to be made as to which chemicals need to be tested, provide some idea as to their toxicity and finally mode of action, and at the same time, taking into account the Three Rs, reduction, refinement and replacement. Thus, specific batteries of tests are not discussed, as these would need to be tailored to the specific chemicals of concern, e.g. endocrine disruptors, HPV. Neither are regulatory requirements factored into the concept, but the data that would be gathered should consider the possibility of eventual submission of the data obtained by in vitro and other non-traditional approaches by regulatory authorities.
EU Sales Ban on New Cosmetics Tested on Animals: Impact on Alternative Methods, WTO Implications and Animal Welfare Aspects
Authors: Ruhdel Irmela W.
Published: April 2019

In 1993, the European Union (EU) adopted Directive 93/35/EEC, calling for a sales ban on new cosmetic products containing ingredients tested on animals after 1 January, 1998, provided that alternative methods had been developed by then. In May 2000, for the second time, the European Commission postponed that ban. The Commission justified the repeated postponement of the sales ban by saying that no animal-free methods were available, although three in vitro methods were scientifically approved in 1997. With three years delay, these methods have been published and therefore “made available” in the EU. OECD acceptance is still awaited. Another reason for the postponement was the fear of possible World Trade Organisation (WTO) conflicts. However, according to WTO rules, the protection of public morality or animal health could justify a restriction of the free trade principle. From the animal welfare point of view, an unqualified EU sales ban, combined with an animal testing ban, would provide the incentive to further promote the development and acceptance of alternative methods and to prove that ethical standards are legitimate concerns under WTO rules.
New Housing Conditions: Improving the Welfare of Experimental Animals
Authors: Ottesen Jan L. , Weber Anett , Gürtler Hanne , Mikkelsen Lars Friis
Published: April 2019

As animal experiments and testing are still a necessary part of the discovery and development of new drugs and do not seem likely to be totally replaced in the foreseeable future, it is important that the care and use of these animals are continuously refined. Since the housing facilities are where most experimental animals spend the major part of their lives, this area should be given special attention to ensure optimal welfare for the animals. In a unique collaboration between a pharmaceutical company and an animal welfare organisation, the housing conditions of mice, rats, guinea-pigs, rabbits and dogs, respectively, were reviewed with focus on the basic needs of the animals. Prototypes for new housing systems satisfying the most important of these basic needs of the animals were developed, with valuable input from international experts with special knowledge of the behaviour of experimental animals. These new housing systems and species-specific, newly introduced socialisation programmes contribute to improved animal welfare and a better occupational health of the animal caretakers. Since these new housing systems are more pleasant and appealing, they may also have the added benefit that they contribute to a broader public acceptance of the use of experimental animals.
Animal Model Research: The Apples and Oranges Quandary
Authors: Shapiro Kenneth J.
Published: April 2019

In this paper, I explore the premises underlying the problem of the evaluation of animal models. I argue that the presence of similarities and differences between the model and the modelled, although historically and currently a dominant antinomy framing evaluation, is not a bottom-line consideration. What is critical is 1) whether we learn and 2) whether we improve treatment through the animal model research. Similarity between model and modelled and the closely related concept of validity are not coterminus with these critical evaluative measures. In fact, differences between the model and modelled also can provide impetus to new understanding and treatment innovations. The apples and oranges argument — that model and modelled are incommensurable — whether based on theoretical or empirical grounds, is not an adequate critique. Continuing argument that relies heavily on similarities versus differences is unconstructive, reducing to the proverbial half-empty/half-full bottle argument.
Achievements in Raising Awareness on the Use of Alternative Methods in Latin America and the Caribbean
Authors: Pérez Luis Ulpiano , Murillo Gisela Antonia , Pascual José Ramón , Tur Enieyis
Published: April 2019

Activities to promote the awareness and acceptance of alternatives in Latin America and the Caribbean were initiated four years ago. As a result, information about the Three Rs has been distributed to students, teachers, researchers and authorities in more than two hundred academic and research centres from seventeen countries. Short courses and lecture series were presented to hundreds of attendees from those sectors. Many educators have already been persuaded of the advantages of using alternatives. So far, models, software and videos have been used, and it is intended that further resources in the Spanish language will be produced to assist the replacement of animal use in practical classes. As an integral part and a remarkable event of the project, the First Caribbean and Latin American Workshop on Alternative Methods was held in Santiago de Cuba in December 2001. In spite of these accomplishments, much still needs to be done in order to increase the use of alternatives in various fields of scientific and educational activity within the region. The commitment is still present and further initiatives will ensue.
An Approach to Minimise Dog Use in Regulatory Toxicology: Production of a Best Practice Guide to Study Design
Authors: Phillips Barry , Smith David , Combes Robert , Descotes Gerard , Jacobsen Soren Dyring , Hack Ruediger , Kemkowski Joerg , Krauser Klaus , Pfister Rudolf , Rabemampianina Yvon , Sparrow Sue , Stephan-Gueldner Markus , von Landenberg Friedrich
Published: April 2019

The primary non-rodent species used in toxicology is the dog. It is generally agreed that, for ethical reasons, dog use should be reduced to the minimum consistent with maintaining the scientific quality of toxicology studies and ensuring human safety. Dog use in toxicology has been discussed widely, both from a scientific and ethical viewpoint, and there appears to be real potential for achieving significant reductions in the number of dogs used in pharmaceutical safety testing. An industry animal welfare initiative commenced in 2000, with the aim of evaluating and, where possible, putting into practice, scientifically valid approaches to minimise dog use in regulatory toxicology without increasing the use of other non-rodent species, such as non-human primates or minipigs. The study's Steering Group categorised potential reduction approaches into three distinct areas, one of which is the production of a best practice guide on aspects of study design, including: group sizes, use of control animals, single sex studies and design of maximum tolerated dose (MTD) studies. Information on current practice and experience within the pharmaceutical industry is now being analysed, and additional input is invited.
Report of the Workshop on Xenotransplantation
Authors: McArdle John
Published: April 2019

Although the basic concept and medical promise of xenotransplantation appears simple, clinical and scientific, realisation has proven elusive, with success unlikely in the near future. Speakers in this workshop discussed the current European perspective on xenotransplantation; the range of clinical protocols under consideration and the health problems they are designed to address; alternative approaches with an emphasis on reducing the need for transplantation, while increasing the supply and utilisation of human organs; and animal welfare aspects of xenotransplantation research and potential clinical applications.
JSAAE Activities in Alternatives to Animal Experimentation for Undergraduate Schools: Forum for Citizens in Primary and Secondary Schools
Authors: Kurosawa Tsutomu Miki , Ninomiya Hiroyoshi , Matsuda Yukihisa
Published: April 2019

The aim of this paper is to introduce some educational activities by the Japanese Society of Alternatives to Animal Experiments (JSAAE). The JSAAE is an academic society to promote the Three Rs in Japan and also the international biomedical community. Our activities include the education of not only scientists but also the public. In particular, activities should be focused on the education in schools regarding alternatives. The JSAAE organised a forum for citizens in alternatives education in primary and secondary schools during their 14th annual meeting.
Medical Training using Simulation: Toward Fewer Animals and Safer Patients
Authors: Balcombe Jonathan
Published: April 2019

This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using animals. The first validation studies of medical simulators began appearing in the late 1990s, and the early results indicate that these devices measure what they are intended to, and that they can improve performance relative to traditional learning methods. In addition to expanded use for new and existing minimally invasive procedures, medical simulators will probably soon be used in physician credentialing, and they may someday allow surgeons to rehearse procedures in a patient-specific operating environment. Replacing animals with simulators in medical training is limited no longer by technical feasibility but by a willingness of the medical community to embrace it.
The ECVAM Scientific Information Service (SIS)
Authors: Roi Annett Janusch , Burke Andrew
Published: April 2019

This article provides a general view about the main Scientific Information Service (SIS) projects and their current status. The SIS was established in 1996, to best achieve one of the four main obligations of the European Centre for the Validation of Alternative Methods (ECVAM), as required by the European Commission and Parliament, to establish and maintain a database on alternative procedures to animal experimentation. Two projects have been carried out: the SIS databases providing factual information on various aspects of animal alternatives and the ECVAM Thesaurus. The first online version of selected SIS databases was published on the Internet in 2001. The ECVAM Thesaurus will be made available for practical applications in 2004, and the general website of the whole ECVAM unit has been available since autumn 2002.
Search Strategies on the Internet: General and Specific
Authors: Bottrill Krys
Published: April 2019

Some of the most up-to-date information on scientific activity is to be found on the Internet; for example, on the websites of academic and other research institutions and in databases of currently funded research studies provided on the websites of funding bodies. Such information can be valuable in suggesting new approaches and techniques that could be applicable in a Three Rs context. However, the Internet is a chaotic medium, not subject to the meticulous classification and organisation of classical information resources. At the same time, Internet search engines do not match the sophistication of search systems used by database hosts. Also, although some offer relatively advanced features, user awareness of these tends to be low. Furthermore, much of the information on the Internet is not accessible to conventional search engines, giving rise to the concept of the “Invisible Web”. General strategies and techniques for Internet searching are presented, together with a comparative survey of selected search engines. The question of how the Invisible Web can be accessed is discussed, as well as how to keep up-to-date with Internet content and improve searching skills.
Reduction through Education: The Insight of a Trainer
Authors: van der Valk Jan , van Zutphen Bert F.M.
Published: April 2019

One of the articles contained within European Council Directive 86/609/EEC states that “Persons who carry out experiments or take part in them, and persons who take care of animals used for experiments, including duties of a supervisory nature, shall have appropriate training”. In effect, this article stipulates that only competent individuals are allowed to work with laboratory animals. At least three groups of individuals can be identified with different responsibilities toward experimental animals: animal technicians, scientists, and veterinarians/animal welfare officers. The responsibilities and duties of the individuals within each of these categories differ. This paper focuses on the training of scientists. The scientist designs, and often also performs, animal experiments. Therefore, scientists must be educated to develop an attitude of respect toward laboratory animals, and must be trained so that, if an experiment must be performed with animals, it is designed according to the highest possible scientific and ethical standards. In The Netherlands, the law stipulates that scientists intending to work with animals must have completed a course in laboratory animal science. This compulsory course started in 1986. The Department of Laboratory Animal Science at Utrecht University is responsible for the national coordination of this course. Participants must have an academic degree (at the level of MSc) in one of the biomedical sciences, such as biology, medicine or veterinary medicine. Although the course is an intensive 3-week, 120-hour long course, which covers both technical and ethical aspects of laboratory animal experimentation, it cannot provide full competence. It is designed to provide sufficient basic training and knowledge to enable students to design animal experiments, and to develop an attitude that will be conducive to the implementation of the Three Rs. However, full competence will always require further training that can only be acquired as a result of practical experience gained while working in the field of laboratory animal research. Evaluations subsequent to the course have revealed that more than 98% of the students regard the course as indispensable for all scientists working in a research area where animal experiments are performed. They agree that the course not only contributes to the quality of experiments and to the welfare of animals, but also to a decrease in the number of animals used in experiments.
Reduction in Laboratory Animal Use by Factorial Design
Authors: Shaw Robert
Published: April 2019

Factorial experimental designs (FEDs) can be used to study the effects of controllable variables, such as an experimental treatment, sex, strain, age, diet and prior treatment of animals, on some defined response. Such designs have been widely used in optimising manufacturing processes, but have rarely been used in optimising animal experiments in drug discovery. FEDs generally provide more information than the alternative “one-variable-at-a-time” approach, because each animal contributes information on the effect of every factor, and because such designs can highlight any interactions among the variables. Although FEDs can have any number of factors and levels of each factor, where many factors are to be explored, it is common to do an initial experiment using two levels of each factor, and in some cases fractional factorial designs can be used to reduce the total number of treatment combinations to manageable levels. These designs have been used successfully at AstraZeneca in the optimisation of in vivo drug screening experiments, where their use has effectively reduced the numbers of animals used in some routine screens.
Opportunities for Reduction in Acute Toxicity Testing via Improved Design
Authors: Whitehead Anne , Stallard Nigel
Published: April 2019

The conventional method for assessing acute oral toxicity (OECD Test Guideline 401) was designed to identify the median lethal dose (LD50), using the death of animals as an endpoint. Introduced as an alternative method (OECD Test Guideline 420), the Fixed Dose Procedure (FDP) relies on the observation of clear signs of toxicity, uses fewer animals and causes less suffering. More recently, the Acute Toxic Class method and the Up-and-Down Procedure have also been adopted as OECD test guidelines. Both of these methods also use fewer animals than the conventional method, although they still use death as an endpoint. Each of the three new methods incorporates a sequential dosing procedure, which results in increased efficiency. In 1999, with a view to replacing OECD Test Guideline 401, the OECD requested that the three new test guidelines be updated. This was to bring them in line with the regulatory needs of all OECD Member Countries, provide further reductions in the number of animals used, and introduce refinements to reduce the pain and distress experienced by the animals. This paper describes a statistical modelling approach for the evaluation of acute oral toxicity tests, by using the revised FDP for illustration. Opportunities for further design improvements are discussed.