bluuebunny/crossref_metadata_2025 huggingface dataset:
The European Resource Centre for Alternatives in Higher Education
Authors: de Boo Jasmijn , Dewhurst David , van der Valk Jan
Published: April 2019

The European Resource Centre for Alternatives in higher education (EURCA: http://www.eurca.org ) is an exciting new project, which aims to enable teachers using animals in teaching to be more creative and innovative in their approach to teaching and learning, to foster high-quality training for science students, and to significantly reduce the number of animals used, often unnecessarily, in teaching. This will be achieved by: a) establishing a resource centre — a collection of mainly electronic alternatives, and taking this to relevant scientific meetings in Europe, where it would function as a drop-in advice centre for teachers; b) creating a network of academic teachers who actively use alternatives, to take responsibility for disseminating information about alternatives to other teachers in the European Union, to participate in the activity outlined above, and to share experiences and good practice; c) setting up an Internet website with an expansive, information-rich database (peer-reviews, demos, peer-evaluations, peer-recommendations, links to users, etc.) on selected “tried and tested” alternatives; and d) encouraging and promoting the findings of evaluative studies on the effectiveness of alternatives in higher education teaching and learning.
Teaching from the Heart
Authors: Walshaw Sally
Published: April 2019

In many countries, training for individuals working with research animals has been mandated for more than 30 years. Required training topics include methods for the proper handling of animals, anaesthesia, surgery, euthanasia, non-surgical procedures (e.g. injections, oral dosing, blood collection), and recognition of animal illness and pain. During training sessions, the instructor, as a role model, should encourage an attitude of respect and kindness toward the animals. By honouring and modelling these values, instructors can expect minimal distress for the laboratory animals during procedures, prompt reporting of unexpected adverse consequences in animals to the veterinarian and the animal care committee, and a strong interest in considering alternatives.
The Regulatory Acceptance of Alternatives in the European Union
Authors: Warbrick E. Vicky , Evans Peter F.
Published: April 2019

Recently, progress has been made toward the regulatory acceptance of replacements in the European Union (EU), particularly with the introduction of in vitro methods for the prediction of skin corrosivity, dermal penetration, phototoxicity and embryotoxicity. In vitro genotoxicity tests are well established, and testing for this endpoint can be completed without animals, provided that clear negative outcomes are obtained. Tiered approaches including in vitro tests can also be used to address skin and eye irritation endpoints. Reductions and/or refinements in animal use are being achieved following the replacement of the oral LD50 test with alternative methods and the adoption of reduced test packages for materials, such as closed-system intermediates and certain polymers. Furthermore, the use of a “read-across” approach has reduced animal testing. Substantial gains in refinement will also be made with the recent acceptance of the local lymph node assay for skin sensitisation and the development of an acute inhalation toxicity method that avoids lethality as the endpoint. For the future, under the proposed EU Registration, Evaluation and Authorisation of Chemicals (REACH) scheme, it is envisaged that, where suitable in vitro methods exist, these should be used to support registration of substances produced at up to ten tonnes per annum. This proposal can only accelerate the further development, validation and regulatory acceptance of such alternative methods.
The FDA's Regulatory Role in the ICCVAM Process
Authors: Schechtman Leonard M. , Stokes William S.
Published: April 2019

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), a permanent body set forth in the ICCVAM Authorization Act of 2000 (Public Law 106-545), is charged with establishing criteria and processes for the validation and regulatory acceptance of toxicological test methods of interest to Federal agencies, including alternative methods that reduce, refine, or replace the use of animals for research and testing purposes. In response to that mandate, 15 Federal regulatory and research agencies and programmes that would consider utilising such methods or the results derived from them, now participate in cross-agency efforts directed toward the identification, standardisation, validation, acceptance, regulatory implementation and international harmonisation and adoption of such test methods. As an integral member of ICCVAM since its inception, the US Food and Drug Administration (FDA) has established processes for responding to ICCVAM issues and recommendations. The participating FDA units include all FDA research and product-based centres and oversight offices. FDA product centres respond to distinct regulatory mandates and regulate different products. Upon completion of a validation effort, ICCVAM forwards its recommendations to member Government agencies regarding the validity and technical acceptability of a method. The FDA's response consists of the conclusions reached by each of its regulatory components and addresses such factors as their concurrence with ICCVAM's conclusions, the practical applicability of the method to the products they regulate and the feasibility of implementation of an accepted method to supplement or supplant those currently used. Each centre/office independently determines which of the ICCVAM-recommended tests are appropriate for implementation to satisfy its regulatory obligations to ensure product safety and to protect human health. The adoption of a method triggers a notification process to announce the availability and utility of a method, encourage its use, and inform, educate and train end-users and regulatory review staff.
Can Hepatoma Cell Lines be Re-differentiated to be Used in Drug Metabolism Studies?
Authors: Martínez-Jiménez Celia P. , Jover Ramiro , Gómez-Lechón Maria José , Castell José V.
Published: April 2019

Knowledge of metabolism, enzymes so far involved, and potential enzyme-inhibiting or enzyme-inducing properties of new compounds is a key issue in drug development. Primary cultured hepatocytes, cytochrome P450 (CYP)-engineered cells and hepatoma cell lines are currently being used for this purpose, but only primary cultures can produce a metabolic profile of a drug similar to that found in vivo and can respond to inducers. Because of their limited accessibility, alternatives to replace human hepatocytes are currently being explored, including the immortalisation of hepatocytes by using different strategies (i.e. SV40 T-large antigen, conditionally immortalised hepatocytes, transfection with c- myc, cH- ras, N- ras oncogenes, transgenic animals over-expressing growth factors or oncogenes and cre-lox recombination/excision). However, none of the resulting cells has the desirable phenotypic characteristics to replace primary cultures in drug metabolisms studies. We investigated why these differentiated human hepatomas do not express CYP genes and found that the levels of certain key transcription factors clearly differ from those found in hepatocytes. It was then conceivable that re-expression of one (or more) of these transcription factors could lead to an efficient transcription of CYP genes. The feasibility of this hypothesis was demonstrated by genetic engineering of Hep G2 cells with liver-enriched transcription factors followed by the analysis of the expression of the most relevant human CYPs.
Ideology Masquerading as Science: The Case of Endocrine Disrupter Screening Programmes
Authors: Seidle Troy
Published: April 2019

The global move to develop novel testing methods and strategies to identify suspected endocrine disrupting chemicals offers a unique opportunity to move away from traditional animal testing paradigms in this new area of regulatory concern. Regrettably, the programmes under development, both in the USA and internationally through the OECD, have thus far failed to consider in vitro and other non-animal test methods as more than “pre-screening” or “priority-setting” tools in a larger, animal-based testing strategy. Validation efforts to date have focused almost exclusively on the modification of existing animal tests to detect “endocrine effects”, with no demonstrable effort to promote international coordination or support for the development and validation of relevant non-animal test systems. The current orientation in these programmes reflects ideological, rather than scientific, imperatives, and undermines the commitments of both the US government and the OECD with respect to the Three Rs and the minimisation of animal testing.
Update on the Validation and Regulatory Acceptance of Alternative Tests for Skin Corrosion and Irritation
Authors: Fentem Julia H. , Botham Philip A.
Published: April 2019

The European Centre for the Validation of Alternative Methods (ECVAM) has supported validation studies on in vitro tests for skin corrosion, resulting in the validities of four alternative tests being endorsed. The US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has also evaluated the validity of these alternative methods for skin corrosion testing. In the European Union, a new Test Method on Skin Corrosion (B.40), incorporating the rat skin transcutaneous electrical resistance and human skin model assays, was included in Annex V of Directive 67/548/EEC in mid-2000. At an international level, two OECD Test Guidelines (430 and 431) on these alternative methods have been approved as of May 2002. To date, there are no validated in vitro tests for predicting the dermal irritancy of chemicals. ECVAM supported prevalidation studies on five in vitro tests for acute skin irritation during 1999–2001. These tests were based on human, pig and mouse skin. However, none of them met the criteria set for inclusion in a large-scale formal validation study. Following additional work on the test protocols and/or prediction models, it appears that several modified tests could now be ready for validation in 2003.
The Bioavailability of Cationic Azo Hair Dyes: Application of a New In Vitro Method
Authors: Steiling Winfried
Published: April 2019

An in vitro technique for the prediction of percutaneous penetration/dermal absorption is recommended by the European SCCNFP (The Scientific Committee on Cosmetic Products and Non-Food Products intended for consumers) for the safety evaluation of particular ingredients. In 2002, this in vitro method became officially accepted at the OECD level and will be published as OECD Guideline 428. Examples are given for its routine application, demonstrating the bioavailability of cationic azo hair dyes out of an aqueous solution compared to data from a realistic standard hair dye formulation. Data from two direct hair dyes, BASIC BROWN 17 and BASIC YELLOW 57, demonstrate the results of applying this new in vitro technique without radiolabelled material. Direct hair dyes are frequently used in semi-permanent cosmetic hair colourations without the additional need for hydrogen peroxide. In the light of the in-house experience over about 5 years in using excised pig skin for measurements of the percutaneous penetration and dermal absorption of hair dyes, the technique was found to be successful and appropriate for reducing the number of test animals normally used for toxicological assessments.
Are Animals Necessary in 2002? Reply to Dr Michael Festing's Book Review of Sacred Cows and Golden Geese: The Human Cost of Experiments on Animals
Authors: Greek Ray , Greek Jean Swingle
Published: April 2019

We appreciate this opportunity to defend the concepts we expressed in 2000, in Sacred Cows and Golden Geese: The Human Cost of Experiments on Animals. Enthusiastic critiques such as Dr Michael Festing's are extremely valuable, if those within and without the field of science are finally to understand, choose among, and embrace viable research modalities that are meant to result in cures and treatments for human disease. Criticisms also help to clarify misunderstandings. We hope this essay will shed light on the debate.
Potential of Comprehensive Toxico-proteomics: Quantitative and Differential Mining of Functional Proteomes from Native Samples
Authors: Schrattenholz André , Klemm Martina , Cahill Michael
Published: April 2019

It is becoming increasingly clear that the interactions of targets and biomarkers, drug modes of action and molecular mechanisms of side-effects and toxic effects are much more complex than previously anticipated, basically due to physiological compensation and cross-talk. Single genes often lead to hundreds or even thousands of functional protein molecules, modified at the post-translational level. Thus, the comprehensive analysis of proteins (proteomics) teaches us that physiological activity means dynamic, multidimensional processes among many thousands of different proteins within higher systems of organisation and correlation. Crucial for control and relevant reduction of this enormous complexity, which will enable new kinds of molecular drug screening, as well as a new type of molecular toxicology, is a consequently differential and quantitative protein analysis. Precise knowledge of key protein isoforms with specific post-translational modifications within kinetic and contextual relationships is accessible by powerful new technologies, which have emerged to analyse the surprisingly ambiguous world of proteins, where single molecular modules are involved in a diversity of often opposing signal transduction pathways in a most flexible way.
Good Experimental Design and Statistics Can save Animals, But how can it be Promoted?
Authors: Festing Michael F.W.
Published: April 2019

Surveys of published papers show that there are many errors both in the design of the experiments and in the statistical analysis of the resulting data. This must result in a waste of animals and scientific resources, and it is surely unethical. Scientific quality might be improved, to some extent, by journal editors, but they are constrained by lack of statistical referees and inadequate statistical training of those referees that they do use. Other parties, such as welfare regulators, ethical review committees and individual scientists also have an interest in scientific quality, but they do not seem to be well placed to make the required changes. However, those who fund research would have the power to do something if they could be convinced that it is in their best interests to do so. More examples of the way in which better experimental design has led to improved experiments would be helpful in persuading these funding organisations to take further action.
Non-invasively Assessing Disturbance and Stress in Laboratory Rats by Scoring Chromodacryorrhoea
Authors: Mason Georgia , Wilson David , Hampton Charlotte , Würbel Hanno
Published: April 2019

In rats, like many rodents, Harderian glands next to the orbits secrete porphyrins, lipids and other compounds. High levels of secretion lead to chromodacryorrhoea (red or “bloody” tears), often taken as a sign of stress or disease. Here, we developed a scoring system for recording chromodacryorrhoea in a quantitative way, and investigated whether the low-level, transient Harderian secretions of normal, healthy rats correlate with low to moderate levels of stress or disturbance. Rather than exposing our subjects (24 Lister Hoodeds, housed in 11 single-sex cages) experimentally to stressors, we made opportunistic use of three likely sources of low-level stress within the unit: 1) building maintenance work, taking several hours and involving several potential stressors; 2) visits by unfamiliar humans, and the other mild sources of disturbance normal in an animal unit; and 3) social status within the cage. The mean daily chromodacryorrhoea score increased most with the severe disturbance of building maintenance work (F1,9 = 602.67, p << 0.0001), and also increased — though to a lesser extent — with the mild disturbance of visitors and similar (F1,9 = 8.77, p = 0.008), while being the subordinate member of a cage-group had a smaller effect still (F1,6 = 7.86, p = 0.03). Individual rats scored consistently across treatment conditions, and there was also significant inter-observer reliability between independent scorers. We therefore suggest that scoring chromodacryorrhoea could be a simple, practical and non-invasive way of sensitively assessing the impact on rats of housing, husbandry, or procedures.
Implanted Telemetry Transmitters Alter the Noradrenergic Response in Vas Deferens from Mice
Authors: Einstein Rosemarie , Billing Robyn L. , Singh Anureet , Chin Irene
Published: April 2019

Implantable telemetry devices are widely used in experimental animals. We investigated the potential for such implants to induce stress in mice. Changes in body weight and post-mortem responses of the vas deferens to noradrenaline (as a measure of sympathetic activation) were measured 28 days after transmitter implantation. We examined the influence of the anaesthetic used during implantation (pentobarbitone or fentanyl/fluanisone/midazolam), the strain (Balb/c and CBA) and the body weight at the time of implantation (small = 19–24g; large = 27–30g). A sham-implantation procedure did not significantly affect the responses to noradrenaline. When telemetry transmitters were implanted in small mice of both strains, there was a significant increase in the maximum response to noradrenaline compared to that obtained in tissues from large mice. The anaesthetic used during implantation did not affect the responses to noradrenaline obtained post mortem. Mice of both strains had a significant post-operative weight loss and this was maintained for the experimental period. The results show that implantation of telemetry transmitters has a significant impact in mice that weigh < 25g.
Effect of Conditioning on the Increase of Heart Rate and Body Temperature Provoked by Handling in the Mouse
Authors: Kramer Klaas , van de Weerd Heleen , Mulder Anne , van Heijningen Caroline , Baumans Vera , Remie René , Voss Hans-Peter , van Zutphen Bert F.M.
Published: April 2019

To assess the effect of procedures on animal welfare, various physiological parameters, such as body weight, hormone levels in plasma and/or urine, heart rate (HR), blood pressure and body temperature (BT), can be used. When measuring physiological parameters with techniques involving restraint of the animals, the results must be interpreted with caution, since restraint itself may have an effect on those parameters. Radio-telemetry, using an implantable transmitter, provides a way to obtain more accurate and reliable physiological measurements from freely moving animals in their own environment. In this study, we have used radio-telemetry to investigate the influence of conditioning on the increase of HR and BT as provoked by handling of mice. It was found that, after a conditioning period of 12 days, the increase of HR due to handling was significantly reduced.
Non-invasive Physiology in Conscious Mice
Authors: Kale Ajit , Amende Ivo , Piskorski Katrina , Chu Victor , Otero Jose M. , Mueller Peter , Hampton Thomas G.
Published: April 2019

Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 ± 0.1 strides/second to walk 18cm/second and have a heart rate of 750 ± 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 ± 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 ± 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 ± 0.3ms vs. 10.4 ± 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.
Reducing the Invasiveness of Obtaining Blood-borne Measures in Animals
Authors: Cook Christian , Thomas David
Published: April 2019

To overcome the limitations associated with routine blood collection methods in welfare research, we are developing a new technique that combines low frequency ultrasound with a small electric current (electrosonophoresis). Portable instrumentation, positioned at the skin surface, delivers a brief burst of ultrasound and low electric field, creating a brief transdermal flux from underlying blood vessels into extracellular fluid and to the skin. The technique allows many analytes present in blood to be collected and measured at the skin surface. In humans, the method is without sensation and is innocuous. Actual blood removal is not required, and repeated measure over a short time period does not cause discomfort. In animals accustomed to human handling, no behavioural disturbance has been seen when using the instrumentation. Large cellular substances, such as red blood cells, cannot be collected by this method, but analytes, including hormones, sugars, free fatty acids, immunoglobulins and lactate, have been collected and measured with a high correlation (r2 ≥ 0.89) to blood levels over a wide physiological range of change. The low invasiveness of use, the removal of the need to extract actual blood fluid, and the low stressfulness of the technique, suggest that this may be a powerful tool for welfare studies.
The Ethics of Research on Companion Animals for the Benefit of Their Own Species
Authors: Conole Jane
Published: April 2019

A fundamental component of the ethics of animal use in science is justification on the basis of a cost–benefit analysis where the cost is to the animals and the benefit is to the same species, another species, the environment or human society. This analysis is the baseline from which research projects can be refined to increase the benefit and reduce the animal cost. Research on companion animal species to the benefit of that species provides some interesting aspects of cost–benefit analysis. These include: the interface between clinical research in animals and the practise of veterinary science; the greater acceptance of animal research that benefits that animal species; and the allied benefits of companion animal research to society, companion animal owners, animal drug and food industries, and so forth. In many cases, these allied benefits are integral to the availability of resources to conduct the work. However, benefit to the companion animal species involved remains an important and welcome aspect of the use of these species in science.
Reduction by Well-defined Objectives
Authors: Fry Derek
Published: April 2019

Examination of programmes of experimental work involving live animals indicates scope for worthwhile reduction in animal usage by identifying more clearly the objectives of the different stages of a programme. Having a defined first objective for new or transferred methodology as “to optimise the methods”, rather than an exploratory “try it with a few animals and modify” approach, is more likely to obtain the conditions for largest divergence between the effect to be measured and the background variability. Where several experiments will use the same methodology, even small improvements in this “signal to noise” ratio may be worthwhile, as the reduction is cumulative. Subdivision to more precise objectives helps concentrate the animal usage. For example, separating “to determine the time of a distinct peak” from “to determine the size of the peak” avoids using the numbers needed to achieve the latter for every time point at which the peak might occur. Similarly, setting a series of objectives for a programme that lead to clear decision points allows setting of clear criteria for achievement at each stage, as well as for the design and analysis to be the most efficient. This paper gives illustrations of the applicability of these arguments and estimates of potential reduction.
Adequate Statistical Methods to Reduce the Number of Animals Used in Behavioural Experiments: The Analysis of the Behavioural Transitions
Authors: Puopolo Maria , Pesciolini Aldina Venerosi , Chiarotti Flavia , Ricceri Laura
Published: April 2019

In ethological and behavioural toxicological studies, elaborate behavioural patterns shown by the animals under well-established experimental paradigms or naturalistic conditions are routinely observed and split into single behavioural items. Subsequently, these items are analysed in terms of their frequencies and/or durations. Behavioural observations are usually videotaped and scored by dedicated softwares, which collect the sequences of behavioural items together with frequencies and durations. So far, the Cox proportional hazards model, a method originally developed for the analysis of time-to-event data, has been employed for the analysis of the time-structure of behaviour, but its usefulness has been limited because of difficulties in including random effects in the model. Recent developments in mixed models for the analysis of time-to-event data may overcome this limitation and improve the analysis of behavioural patterns. Data from social interactions in mice on the effects of exposure to chlorpyrifos, a widely used organophosphorous pesticide, are presented to illustrate the use of these new statistical methods. Our results suggest that the study of behavioural sequences may highlight the role of the investigated conditions (treatments, genetic condition, social status) in setting behavioural organisations. In addition, the refinement of statistical methods by time-structured analysis provides more detailed information from an experimental data set, thus contributing to the reduction of the number of animals used in this field of the life sciences.
Animal Use Statistics: The New Zealand and Australian Experience and Perspective
Authors: Bayvel A.C. David
Published: April 2019

Both New Zealand and Australia have established systems for the collection, collation, analysis and publication of animal use statistics. In New Zealand, the collection of national data was first mandated in 1987, and has been continued by regulations made under the recently introduced Animal Welfare Act 1999. Initially, the information collected in New Zealand was of a very general nature. During the early 1990s, the National Animal Ethics Advisory Committee (NAEAC) played a key role, working with the Ministry of Agriculture and Forestry (MAF), to revise the information required to ensure that it was more meaningful and informative. This process of revision and refinement has been ongoing, with an independent research report being commissioned on behalf on both MAF and NAEAC in 2000. A number of specific issues currently receiving attention are referred to in this paper, along with more general issues arising from moving to more informative and transparent systems. The value of animal use statistics was addressed by a Senate Select Committee in Australia in 1989, when it was recommended that a summary of the animals used in teaching and research in each State and Territory be collated on a national basis. An initiative has been taken to achieve this objective, although delays have resulted from a number of legal, policy and logistical issues.
An Evaluation of the US High Production Volume (HPV) Chemical-testing Programme: A Study in (Ir)Relevance, Redundancy and Retro Thinking
Authors: Nicholson Andrew , Sandler Jessica , Seidle Troy
Published: April 2019

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines issued by the EPA in October 1999. Our review found major and recurring flaws in the programme's execution, as well as in its fundamental design. Approximately 75% of the test plans reviewed violated fundamental terms of the programme. Many participating companies failed to conduct comprehensive analyses of available data and instead proposed superfluous and meaningless tests. The US HPV programme's exclusion of human health and exposure data has led to numerous examples of irrelevant experiments that will not affect how a chemical substance is used or handled. Contrary to claims by both the EPA and Environmental Defense that few new animal tests are being performed, an estimated 100,000 animals have already died in this US Government-sponsored animal-testing programme.
The HSUS's Pain and Distress Initiative: Overview and Update
Authors: Stephens Martin L. , Conlee Kathleen M.
Published: April 2019

The Humane Society of the United States (HSUS) publicly launched its Pain and Distress Initiative in 2000, to encourage greater attention to the prevention and alleviation of pain and distress in research animals. The initiative's ultimate goal is the phasing out of all significant pain and distress in animal research by 2020. There have been several developments to date. A survey conducted for The HSUS revealed that Americans strongly oppose the use of animals in experiments that cause them to suffer. The HSUS has begun producing a newsletter, The Pain & Distress Report, distributed periodically to over 2000 Institutional Animal Care and Use Committees, scientists and regulators. In 2000, the US Department of Agriculture issued a proposal to upgrade the regulation and reporting of pain and distress. We have challenged the leading research institutions over their under-reporting of unrelieved pain and distress in animals. We have written a comprehensive critique of CO2 euthanasia, arguing that it causes avoidable pain and distress in animals. The National Institutes of Health has issued new guidance on CO2 euthanasia. These developments lay the groundwork for a sustained effort to eliminate animal suffering in research.
Ethical Evaluation of Research Proposals by Ethics Panels Advising the European Commission
Authors: Kolar Roman
Published: April 2019

Ethical principles with regard to animal experimentation are referred to in European Union (EU) legislation and other official documents. Therefore, applications for funding of research under the EU's research programme may undergo an ethical review that is carried out by so-called ethics panels, consisting of experts chosen by the European Commission. The work of these panels differs substantially from that of other ethical committees, as they exist on the institutional, local, regional or national level. Their main purpose is not to decide whether a proposed research can be regarded legal, and therefore should be endorsed or licensed; instead, it is to help the Commission in prioritising its funding. The panels may examine other ethical aspects than those of animal experimentation or animal welfare alone, such as the use of human volunteers. This is reflected by the composition of the panels. Their decisions are normally based on consensus. Even though these decisions may refer to EU legislation, the criteria applied are not restricted to those provided by this legislation. Nevertheless, the various aspects of the Commission's ethical evaluation system (e.g. formal and practical basic conditions, information content of applications, type of decisions taken, lacking of any quality control) offers opportunities for improvement.
Activities in German-speaking Countries (Germany, Austria, Switzerland) to Transform School Education with the Objective of Increasing Student Awareness of Animal Welfare Issues
Authors: Luy Joerg , Grune Barbara
Published: April 2019

While harmful live-animal procedures in primary and secondary schools are illegal in Germany, Austria and Switzerland, and classroom dissections are either illegal or at least unpopular, there is a relatively new trend in German-speaking schools to handle animal welfare issues by means of voluntary animal welfare lessons. This began in the 1980s, and there is now a growing number of (at this point, more than ten) organisations in German-speaking countries offering such classes and/or well-prepared teaching aids. Apart from outlining the legal situation for animal use in education and training, the different educational concepts for animal welfare as a subject in schools are presented.
New Alternative to Animal Models for Surgical Training
Authors: Aboud Emad , Suarez Carlos Ernesto , Al-Mefty Ossama , Yasargil M. Gazi
Published: April 2019

Laboratory training models are essential for developing and refining surgical skills, especially in microsurgery. A perfect training model is the one that can provide the same situation during surgery, in the same anatomy; the closer to live surgery the model is, the greater the benefit. The lack of an accurate vascular model has sometimes necessitated the use of live models when bleeding, and vascular liquid filling is desired for optional learning. We developed a new model utilising human cadavers that can replace the use of live anaesthetised animals for surgical training. The vessels in a cadaveric specimen were connected to artificial blood reservoirs. The arterial side was connected to a pump to provide pulsating pressure inside the arteries, while the venous side was kept under static pressure that applied to the reservoir. This method provides a condition that simulates live surgery in terms of bleeding, pulsation and liquid filling of the vascular tree. It is an excellent alternative model and can be applied to the whole cadaver or to a particular cadaveric specimen (head, arm, leg) or to an isolated organ. It is distinctive and of a great practical value for training in a wide range of surgical procedures, Utilising this technique could forever eliminate the use of live anaesthetised animals for surgical training. The model and device are patent pending application no. 10/339,053.
Replacement of Harmful Animal Use in Life Science Education: The Approach and Activities of InterNICHE
Authors: Jukes Nick
Published: April 2019

Harmful animal use in undergraduate education is increasingly being replaced by alternatives, such as computer software, manikins and simulators, ethically sourced animal cadavers, apprentice work with animal patients, and student self-experimentation. Combinations of such alternatives can better meet teaching objectives, reduce costs and avoid the negative pedagogical and social impact of animal experimentation. Since 1988, the International Network for Humane Education (InterNICHE, formerly EuroNICHE) has been working with teachers to replace harmful animal use and has been supporting students’ right to conscientious objection. This paper presents the approach, history and current activities of InterNICHE. With a vision of 100% replacement, the network aims for empowerment by networking information and providing support. It works with the belief that most teachers want investment in the best quality and most humane education possible. The forthcoming second edition of the InterNICHE book, from Guinea Pig to Computer Mouse, 1 includes practical details of progressive teaching aids and approaches, as well as case studies from teachers who employ such alternatives. In 1999, InterNICHE produced the film Alternatives in Education, now available in 20 languages. Such resources are complemented by outreach trips and conferences and an Alternatives Loan System, which offers products for familiarisation and assessment. The InterNICHE website ( www.interniche.org ) was launched in 2001.
Computer-based Alternatives to Using Animals in Teaching Physiology and Pharmacology to Undergraduate Students
Authors: Dewhurst David
Published: April 2019

In the UK, the majority of animals used for undergraduate education are for laboratory practical classes (wet labs) in pharmacology and physiology. Computer simulations, which are now widely available at relatively low cost, can provide a dry lab experience that may fulfil some, but not all, of the objectives of the animal labs and may be particularly appropriate where the animal lab is costly to run or requires a high level of technical expertise. Broadly, the computer simulations fall into two categories, each having design features in line with achieving slightly different learning objectives. Most of the available evidence suggests that where computer simulations are used as alternatives, they can fulfil many of the learning objectives of wet labs, though clearly they are not effective in teaching animal handling, surgical/dissection and laboratory skills.
The European Science Foundation: Three Rs Policy and Education
Authors: van Zutphen Bert F.M.
Published: April 2019

The European Science Foundation (ESF) has adopted a position paper on the use of animals in research. In this document, the ESF sets out its view on conditions that must be met to make the use of animals morally acceptable. The ESF explicitly states that laboratory animals have an intrinsic value that must be respected. The consequences of recognising the intrinsic value have been elaborated in the position paper and include, among others, that ESF Member Organisations are encouraged to endorse the reduction, refinement and replacement principles. Prior to the performance of an animal experiment, the protocol should be subjected to independent expert review, including the weighing of the likely benefit versus the likely animal suffering. Also, the development and organisation of accredited courses on laboratory animal science, including information on animal alternatives, welfare and ethics, are encouraged. The Council of Europe and the Federation of Laboratory Animal Science Associations have issued recommendations as to the education and training of persons involved in animal-based research. The ESF guidelines are in line with these recommendations. The recommendations are explained, and some details on the implementation in The Netherlands are presented.
ResearchTraining.org and AALASLearningLibrary.org: Online Learning Management Systems for Technicians, Researchers, and IACUCs
Authors: Duffee Nicole , Fallon Michael T.
Published: April 2019

ResearchTraining.org and the AALASLearningLibrary.org are web-based learning management systems that utilise database architecture in Microsoft SQL Server 2000 and Internet browsers (Microsoft Internet Explorer 6.0, Netscape Navigator 6.0 browsers). Both websites are constructed of active server pages coded with a combination of HTML and Visual Basic. Course content, self-assessment quizzes, and exams are displayed on web pages by accessing the system database. Both systems define three client levels: users who take courses and exams, content authors/editors who build and modify courses and exams, and institutional administrators who access training transcripts of staff (singly or in groups). Exams are generated out of pools of questions, from which questions are randomly selected, and the sequence of answer choices are randomised. Users may output their passing exam results to a certificate generator. Passing exam results are also stored in the database for access by users or authorised institutional administrators. These systems are customisable for addressing the training documentation requirements in animal research facilities.
Developing Ethics Training for Laboratory Animal Users
Authors: Jennings Maggy , Smith Jane
Published: April 2019

Consideration of ethical aspects should be an integral part of training for all laboratory animal users, but it is sometimes difficult to decide what exactly this component of training should encompass and/or how it should be approached. A particular question is how to make ethics training more relevant and applicable to the day-to-day work of researchers. This paper briefly summarises thoughts on how ethics training can best be approached, bearing these questions in mind. Although the specific issues are approached in the context of the UK modular training system, the broad principles are applicable to ethics training in any country. The importance of ensuring that ethics training is practically focused and takes place at an early stage in a scientist's education and career is emphasised.
New Sources for Alternative Methods on the Internet: The Objectives of Databases and Web Sites
Authors: Grune Barbara , Dörendahl Antje , Köhler-Hahn Dorothea , Feuerstein Céline , Box Rainer , Wohlgemuth Heinz , Spielmann Horst
Published: April 2019

One of the main requirements of the current animal welfare legislation in Europe is to prove the necessity of performing a given experiment with animals. Thus, a study using animals should not proceed, if another scientifically reliable method is available to obtain the desired results that either avoids animal experiments altogether, minimises pain and suffering of animals or reduces the number of animals needed. Scientists are legally required to search the literature and other relevant sources for alternatives prior to any experimental study with animals. Access to information has become much easier since the introduction of the Internet as a standard tool. Today, a variety of online sources is available, e.g. web-based bibliographic databases and specialised web sites providing details about alternatives to animal studies. However, scientists still need to determine the most appropriate searching strategies, depending on the objectives of the relevant web sites and their own line of research. A critical discussion of this issue takes into account the objectives of both the information providers and the information retrieval systems.
Proposal for International Recognition, Support and Cooperation with the Internet Clearinghouse on the Three Rs (Altweb)
Authors: Libowitz Lisa A.
Published: April 2019

This presentation will focus on the establishment and current international scope of Altweb, the clearinghouse of resources and information about the Three Rs. The need for an international central reference point was established by the European Centre for the Validation of Alternative Methods workshop number 25, which was followed by the development and implementation of Altweb through a Project Team. The growth of the Project Team to include representatives from several European countries and Canada, in addition to widespread support in the USA, and the Project Team's role in shaping this important resource will be discussed, as well as the role Altweb will continue to play in spurring the development of information resources on the Three Rs at an international level. Ways of encouraging use and reducing redundancy with other information providers are explored. A proposal will be introduced to initiate annual meetings in the field of information resources.
Activities in Japan and Other Asian Countries & Summary of the Satellite Session
Authors: Kurosawa Tsutomu Miki
Published: April 2019

In Japan, the main alternative activities are led by the Japanese Society of Alternatives to Animal Experiments (JSAAE). Therefore, the activities of the JSAAE are discussed as representative of Japanese activities. The JSAAE was established in 1982, as an academic society. Since then, the JSAAE has developed gradually, and it now has 338 memberships and 13 supporting organisations. The JSAAE annually publishes Alternatives to Animal Testing and Experimentation ( AATEX) as its official journal, in English. For communication among members and the distribution of information, we regularly publish the newsletter of the JSAAE in Japanese.
Situation in the Czech Republic: An Example of a Country in Transition
Authors: Červinka Miroslav
Published: April 2019

Exploring alternatives to laboratory animals in education is less important in the context of the number of animals used than from the point of view of society's attitude toward this issue. The situation at the Faculty of Medicine in Hradec Králové has changed, mainly as a result of a Joint European TEMPUS Project. The most important result of this project was general incorporation of alternatives into the curricula at our faculty. There are several standard features of the curricula at the Faculty of Medicine in Hradec Králové: no use of dead animals for dissections; no use of animals for surgical training; no harmful use of living animals; clear and thorough consideration of the advantages and disadvantages of alternatives; and practical experience with alternative in vitro methods for each student.
Environmental Enrichment: Room for Reduction?
Authors: Van de Weerd Heleen A. , Van Loo Pascalle L.P. , Baumans Vera
Published: April 2019

Environmental enrichment strategies are usually regarded as refinement. However, when the welfare of animals is enhanced through successful enrichment programmes, a reduction in the number of animals needed can be expected, because fewer animals might be lost during the course of experiments. Several examples of studies where enrichment can lead to reduction will be presented. They include the beneficial effects of nesting material for laboratory mice, the effects of husbandry procedures on controlling aggressive behaviour in male laboratory mice, and the effects of enrichment on variation in the results of experiments.
The Need for a Formal Invalidation Process for Animal and Non-animal Tests
Authors: Balls Michael , Combes Robert
Published: April 2019

A plethora of regulations require that many chemicals and chemical products are tested for efficacy and/or toxicity. When permitted to operate effectively and without bias, the ECVAM/ICCVAM/OECD validation process can be used to independently establish that new animal and non-animal test procedures are sufficiently relevant and reliable for their stated purposes and should be considered for regulatory use. However, the validation process is under threat because of vested interests of various kinds, and it is clear that many currently-accepted animal tests and candidate animal and non-animal tests do not, and could never, meet the agreed criteria for necessity, test development, prevalidation, validation and acceptance. We therefore need an invalidation process to parallel and protect the validation process, so that such methods could be independently reviewed and declared irrelevant and/or unreliable for their claimed purposes. An additional advantage of such a process would be that valuable resources would no longer be wasted in attempts to secure the acceptance of inherently inadequate tests.