Showing papers in "Atla-alternatives To Laboratory Animals in 1995"
TL;DR: This model reproduces very closely the dynamic conditions based on the in vivo situation in monogastric animals and man, which can be an important tool in studying the fate of ingested components during gastrointestinal transit and, consequently, may contribute to the replacement of studies using laboratory animals.
Abstract: A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of t...
621 citations
TL;DR: The European Centre for the Validation of Alternative Methods, a recognised validation authority, now proposes to introduce this prevalidation scheme into its validation strategy.
Abstract: Experience has shown that the outcome of large and expensive validation studies on alternative methods can be compromised if their managers do not insist that optimised test protocols and proof of ...
156 citations
TL;DR: The search for candidates for the next generation of stem cell transplant recipients in Europe is focused on Italy, with a focus on the areas of central Italy and south-east Europe.
Abstract: 3ECVAM, JRC Environment Institute, 21020 Ispra (Va), Italy; RITOX, Utrecht University, P.O. Box 80.176, 3508 TD Utrecht, The Netherlands; Procter & Gamble Health & Beauty Care Europe, Rusham Park, Whitehall Lane, Egham, Surrey TW20 9NW, UK; FRAME, Russell & Burch House, 96-98 North Sherwood Street, Nottingham NGl 4EE, UK; 7Department of Pharmaceutical Biosciences, Uppsala University, Division of Toxicology, Box 594, S-751 24 Uppsala, Sweden; Department of Health, HEF(M) Division, Skipton House, 80 London Road, London SEl 6LW, UK; INSERM U49, Unite deRecherchesHepatologiques, Hopital Pontchaillou, 35033 Rennes, France; ZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SKI 0 4T J, UK; 11 BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK; SIAT In Vzi'ro Toxicology, Technopark, Pfingstweidstrasse 30, CH-8005 Zurich, Switzerland; National Institute of Toxicology, P.O. Box 863, 41080 Seville, Spain; Department of Transplantolof.J?'• Institute of Biostructure/ Medical School, Chalubinskiego 5, 02-004 Warsaw, Poland; 1 ZEBET, Bundesinstitut fur gesundheitlichen Verbraucherschutz und Veteriniirmedizin (BgVV), Diedersdorfer Weg 1, D-12277 Berlin, Germany; Biomedical Technologies InstituteCNR, Via GB Morgagni 30/E, 00161 Rome, Italy
143 citations
TL;DR: This dissertation aims to provide a history of web exceptionalism from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which Bert F.M.W.O.S. van Zutphen died.
Abstract: Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festin~¥ John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennin~s, 0 Margot D.O. van der Kamp, 11 David B. Morton, 12 Andrew N. Rowan, 3 Claire Russell, 14 William M.S. Russeli, 14 Horst Spielmann_, 15 Martin L. Stephens, 16 William S. 17 0 18 4 Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo and 19 Bert F .M. van Zutphen
133 citations
TL;DR: This research presents a novel and scalable approach called “SmartPharm,” which aims to provide real-time information about the safe and effective use of these drugs in the context of clinical practice.
Abstract: MRC Experimental Embryology and Teratology Unit, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK; ZEBET, BgW, Diedersd01fer Weg 1, 12277 Berlin, Germany; Sandoz Pharma Limited, Drug Safety Assessment, 4002 Basle, Switzerland; Bristol-Myers Squibb, Pharmaceutical Research Institute, 6000 Thompson Road, Syracuse, NY 13221, USA; 7SmithKline Beecham Consumer Healthcare, StGeorge's Avenue, Weybridge, Surrey KT13 ODE, UK; 8Department of Histology and Emb1yology, 3rd Medical Faculty, Charles University, Ruska 87, 100 00 Prague 10, Czech Republic; Freie University of Berlin, Institute for Toxicology and Emb1yopharmacology, Gmystrasse 5, 1000 Berlin 33, Germany; GlaxoWellcome Research and Development, Genetic and Repl'Oductive Toxicology, Ware, Herts. SG12 ODP, UK,· 11Huntin;;don Research Centre, Department of Toxicology, Huntingdon, Cambs. PElS 6ES, UK; RhOne-Poulenc Rorer, Drug Safety NW 9, 500 Arcola Road, Collegeville, PA 19426-0107, USA; 1•1Rh6ne-Poulenc, Secteur Agro, 06903 Sophia Antipolis Cedex, France; BgVV, Thielallee 88-92, 14191 Berlin, Germany; 15National Institute of Public Health, Department of Environmental Medicine, Geitmyrsveien 75, 0462 Oslo 4, Norway
88 citations
TL;DR: The application of the Three Rs of humane experimental technique to the production and testing of vaccines, the education of experimenters in laboratory animal science, and the replacement of animals in teaching by the use of computers and audiovisual displays are developed.
Abstract: In 1955–57, in the course of a study initiated by Charles Hume and the Universities Federation for Animal Welfare, Rex Burch and I conceived of the Three Rs of humane experimental technique — repla...
81 citations
Journal Article•
66 citations
TL;DR: The validation process itself evolved as a result of practical experience, and processes such as catch-up validation, weight-of-evidence validation, QSAR model validation and integrated testing strategies came to be seen as important.
Abstract: As non-animal toxicity tests began to be developed in the late 1980s, the need for their validation, i.e. the independent assessment of their relevance and reliability for particular purposes, was recognised, and international discussions on the principles of validation and their practical application took place, notably, in Europe and the USA. This came to involve recognition of a prevalidation stage to ensure that a method was ready for formal validation and of a prediction model, an unambiguous algorithm for converting test data into a prediction of a relevant in vivo pharmacotoxicological endpoint. By the mid-1990s, validated non-animal methods could be proposed for the development of test guidelines and for regulatory acceptance. Meanwhile, the validation process itself evolved as a result of practical experience, and processes such as catch-up validation, weight-of-evidence validation, QSAR model validation and integrated testing strategies came to be seen as important. Major roles in these developments were played by ECVAM in Europe, ICCVAM in the USA, JaCVAM in Japan, and the OECD, but validation centres now operate in a number of other countries.
50 citations
TL;DR: The influence of toxic agents derived from biomaterials on cellular functions and cell viability can be characterised by reductions in cell adhesion, alterations in cellular morphology, reduced cellular proliferation, and cell death.
Abstract: Biocompatibility is one of the main prerequisites for the clinical use of biomaterials. Central to the testing of biocompatibility is the estimation of cytotoxicity, which can be assessed in vitro ...
46 citations
41 citations
TL;DR: By using the method presented here, liver slices from these species can be stored while maintaining viabilities similar to initial values, and this method will facilitate the optimal use of liver slices and reduce the number of experimental animals used.
Abstract: A method for the long-term storage of liver slices by cryopreservation was developed. The viability of liver slices was determined by analysing the leakage of alanine aminotransferase, urea product...
TL;DR: Environmental Safety Laboratory, Unilever Research, Colworth House, Sharnbrook,Bedford MK44 1LQ, UK; Unidad de Hepatologia Experimental, Hospital Universitario La Fe, Avda de Campanar 21, 46009 Valencia, Spain.
Abstract: Environmental Safety Laboratory, Unilever Research, Colworth House, Sharnbrook,Bedford MK44 1LQ, UK; Unidad de Hepatologia Experimental, Hospital Universitario La Fe, Avda de Campanar 21, 46009 Valencia, Spain; FRAME, Russell & Burch House, 96-98 North Sherwood Street, Nottingham NG1 4EE, UK; School of Pharmacy, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK; ECVAM, JRC Environment Institute, 21020 Ispra (Va), Italy; Bundesinstitut fur gesundheitlichen Verbraucherschutz und Veterinarmedizin (BgVV), Thielallee 88-92,14195 Berlin, Germany; Istitutodi R icercasulla Senescenza, Sigma-Tau, Via Pontina, km 30.400, 00040 Pomezia, Italy; Sanofi Research Division, Alnwick Research Centre, Alnwick, NorthumberlandNE66 2 JH, UK;ChemQuest, Cheyney House, 19-21 Cheyney Street, Steeple Morden, Herts. SG8 OLP, UK; ZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SKI 0 4TJ, UK; TNO Nutrition and Food Research Institute, Division of Toxicology, P.O. Box 360, 3700 AJ Zeist, The Netherlands; Research Institute of Toxicology (RITOX), Utrecht University, P.O. Box 80.176, Yalelaan 2, 3508 TD Utrecht, The Netherlands; SIAT, Missionsstrasse 60, 4055 Basel, Switzerland
TL;DR: Significantly lower concentrations of MeHg, acrylamide and TET than the IC20 values were sufficient to induce axonopathy, and inhibition of cell growth was similar in HeLa cells, suggesting a parallel to the documented neurotoxic mechanism of lindane.
Abstract: The effects of the neurotoxic compounds acrylamide, triethyltin chloride (TET), methyl mercury (II) chloride (MeHg) and lindane on selected neurospecific and general cell functions in differentiated human neuroblastoma SH-SY5Y cells were investigated in an attempt to determine critical cellular neurotoxic concentrations. The cultures were exposed to the neurotoxicants for three days, and then the effects on cell growth, neuronal signal transaction and the induction of axonopathy were measured. For comparison, general cytotoxicity was also determined in human epithelial (HeLa) cells. The cytotoxic activities (IC20 values) in the SH-SY5Y cells were 0.18 ± 0.03μM for TET, 0.20 ± 0.03μM for MeHg, 32 ± 10μM for lindane and 810 ± 170μM for acrylamide. Inhibition of cell growth was similar in HeLa cells. Significantly lower concentrations of MeHg, acrylamide and TET than the IC20 values were sufficient to induce axonopathy. In addition, MeHg and acrylamide increased the basal intracellular free calcium concentration, [Ca2+]i, as well as the carbachol-induced Ca2+ fluxes and the depolarisation-stimulated increase of [Ca2+]i compared to control cells. The elevated [Ca2+]i may be a primary cause of the acrylamide-induced and MeHg-induced neuropathy. Treatment with lindane (1μM) slightly decreased the depolarisation-evoked Ca2+ influx in the neuroblastoma cells. A parallel to the documented neurotoxic mechanism of lindane (i.e. inhibition of the γ-aminobutyric acid-activated Cl- channels) is possible.
TL;DR: The study found that in most departments the CAL packages were used in a staff-supervised learning situation, to either replace or support a practical class, and it was also clear that their use had contributed to a significant reduction in animal use.
Abstract: — The impact of computer-assisted learning (CAL) packages on the use of animals in university teaching has been investigated in universities in the UK and abroad. The pilot study has focused on two...
TL;DR: This review attempts to provide an introduction to the complicated subject of refinement, the third R in the concept of alternatives, with a brief discussion of what refinement means and the lack of specific attention paid to this third R.
Abstract: This review attempts to provide an introduction to the complicated subject of refinement, the third R in the concept of alternatives. It starts with a brief discussion of what refinement means and the lack of specific attention paid to this third R. This is followed by an analysis of the conceptual underpinnings of pain, distress and suffering, and the problems of both definition and measurement which must be faced if we are to be objective and consistent in our search for refinement. The review then touches upon husbandry, care and handling issues as they affect animal discomfort and distress. Antibody production, both polyclonal and monoclonal, is discussed as an example of the refinement of research techniques. Finally, a few brief comments are offered on the refinement of a variety of other experimental techniques, including those used in toxicology, cancer research and behavioural research.
TL;DR: A number of in vitro tests, including the kenacid blue, neutral red release and fluorescein leakage assay methods, have been evaluated and have subsequently been included in validation schemes organised by the US Soap and Detergent Association, the US Cosmetic, Toiletry and Fragrance Association and the European Commission.
Abstract: This review outlines the work which has been conducted in the FRAME Alternatives Laboratory during the first ten years of the FRAME Research Programme. A number of in vitro tests, including the kenacid blue, neutral red release and fluorescein leakage assay methods, have been evaluated and have subsequently been included in validation schemes organised by the US Soap and Detergent Association, the US Cosmetic, Toiletry and Fragrance Association, the European Commission and the European Cosmetic, Toiletry and Perfumery Association, as well as in the Scandinavian multicentre evaluation of in vitro cytotoxicity testing scheme. More recently, research has been undertaken in the areas of phototoxicity, immunotoxicity, dermal toxicity and intercellular communication, in addition to investigations into fundamental mechanisms of toxicity.
TL;DR: The concept of “reduction” has been useful in focusing attention on the need for improved experimental design, and in the long-run, animal welfare legislation and improved training for research scientists should lead to improvements, not only in the way in which animals are kept, but also in the ways in which experiments are planned and analysed.
Abstract: “Reduction” in animal use can be achieved by better experimental strategy and improved experimental design. In 1959, one strategy for discovering new drugs involved the random testing of thousands of chemicals in animal models of disease. This strategy was deplored by Russell & Burch in The Principles of Humane Experimental Technique (1959) as being inefficient and inhumane, and has now been almost completely superseded, following fundamental research resulting in an improved understanding of the mechanisms of drug action. Random screening is still done on a large scale, but by using in vitro methods. Good experimental design involves the control of variation. In 1959, it was not clear whether isogenic (inbred or F1 hybrid) strains of mice and rats were more uniform than outbred stocks and whether they should therefore be used preferentially in bioassays. It is now generally accepted that F1 hybrids and inbred strains tend to be more uniform, but, as precision also depends on sensitivity, which is unpredictable, there is no general rule for choosing the best strain for a bioassay. Choice should be based on pilot studies. However, the use of more-uniform, specific pathogen-free animals, which were only just becoming available in 1959, has certainly reduced the number of animals which are used. Other aspects of experimental design, such as the need to avoid bias, have a wide range of applicability; the importance of simplicity and the ability to calculate uncertainty are, apparently, not always appreciated by research scientists. The concept of “reduction” has been useful in focusing attention on the need for improved experimental design. In the long-run, animal welfare legislation and improved training for research scientists should lead to improvements, not only in the way in which animals are kept, but also in the way in which experiments are planned and analysed.
Journal Article•
TL;DR: A historical database containing the results of 294 defined single substances tested in the guinea-pig maximisation test was used to derive a set of structural alerts for skin sensitisation, which have been incorporated into the expert system, DEREK, and are expected to give useful predictions of skin corrosivity and eye irritancy for new or untested chemicals in these classes.
Abstract: A historical database containing the results of 294 defined single substances tested in the guinea-pig maximisation test, carried out according to a single protocol, was used to derive a set of structural alerts for skin sensitisation, which have been incorporated into the expert system, DEREK. Together with an assessment of percutaneous absorption, this system forms an integral part of a strategic approach to the identification of contact allergens. Quantitative structure-activity relationships (QSARs) were derived for the skin corrosivity of organic acids and bases, and for the eye irritation potential of neutral organic chemicals. The independent variables used for these analyses were selected on the basis of the putative mechanisms for skin irritation or corrosivity and for eye irritation, respectively. Data sets were analysed using principal components analysis; plots of the first two principal components for each data set showed that the analyses were able to discriminate well between chemicals with different classifications of toxicological activity. The derived QSARs are expected to give useful predictions of skin corrosivity and eye irritancy for new or untested chemicals in these classes. Although the development of these techniques is still at a very early stage, they are already able to play an important part in proposed strategies for the reduction of experimental animal usage. In the long term, it should be possible to conduct safety evaluations using fewer experimental animals or no animals at all. However, acceptance by regulatory authorities will be a key factor in realising the full benefits of the approach.
TL;DR: This article describes, from a personal viewpoint, some of the major advances in refinement in animal experimentation over the past 25–35 years.
Abstract: This article describes, from a personal viewpoint, some of the major advances in refinement in animal experimentation over the past 25–35 years. It is written mainly from a UK perspective. Aspects of public perception and policy, education and training, and the competence of those involved in animal research, are commented upon. Recognition of adverse effects on animals is seen as the key to the refinement of animal experimentation. Elaboration on, and examples of, this theme are given by referring to refinements in animal husbandry and experimental technique. A brief look forward to the changes that may occur in the next 25 years is also included.
TL;DR: This is very much a personal interpretation of the Three Rs and the efforts by scientists connected with the more humane use of animals to illustrate that scientists are given a job to do and, if it involves animals, they have little choice but to use them.
Abstract: This is very much a personal interpretation of the Three Rs and the efforts by scientists connected with the more humane use of animals. It is intended to illustrate that scientists are given a job to do and, if it involves animals, they have little choice but to use them. It is also intended to illustrate that so many of those so involved are the very people who have made gigantic efforts in finding ways of replacing, reducing and/or refining techniques which require animals.
TL;DR: Department of Medicine & Therapeutics and Department of Biomedical Sciences, Polwarth Building, University of Aberdeen, Aberdeen AB9 2ZD, UK; Faculty of Science, Universityof East London, Romford Road, London E15 4LZ, UK.
Abstract: Department of Medicine & Therapeutics and Department of Biomedical Sciences, Polwarth Building, University of Aberdeen, Aberdeen AB9 2ZD, UK; Faculty of Science, University of East London, Romford Road, London E15 4LZ, UK; LADCR, Division of Toxicology, Center for Rio-Pharmaceutical Sciences, Leiden University, 2300 RA Leiden, The Netherlands; Universitat Wurzburg, Versbacherstrasse 9, 97074 Wurzburg, Germany; /nstitut de Pharmacologie et de Toxicologie de l'Universite, rue de Bugnon 27, 1005 Lausanne, Switzerland; 8Sanofi-Winthrop Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, UK; ZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SKID 4TJ, UK; Department of Biological Sciences, University of Paisley, High Street, Paisley PAl 2BE, UK; /NSERM U295, Uer Medicine Phar.macie, Universite de Rouen, 76803 Saint Etienne Rouvray, France; /nstitut'filr Physiolo1ie zmd Balneologie, Universitiit Innsbruck, Fritz-Preglstrasse 3, 6010 Innsbruck, Austria; 3TNO Nutrition and Food Research Institute, Division of Toxicology, 3700 AJ Zeist, The Netherlands; 14Department ofs Pharmacology, University College Dublin, Fosters Avenue, Blackrock, Dublin, Ireland; 5Rh0ne-Poulenc Rorer, Centre de Recherche de Vitry, 13 Quai Jules Guisde, 94405 Vitry Cedex, France; /nstituto di Medicina del Lavoro, Universita di Padova, Via Facciolati 71, 35127 Padova, Italy
TL;DR: Evidence is presented that reduction of the tetrazolium dye, MTT, is a measure of nucleotide redox balance in hepatocytes, rather than of mitochondrial performance as previously believed.
Abstract: Two conventional systems — freshly-isolated hepatocytes and hepatocytes in culture — are now widely used for toxicity testing, each possessing advantages and disadvantages. More-recently. developed...
TL;DR: In some countries, specific requirements for the education of biomedical research and testing have been defined as mentioned in this paper, which is a highly effective way of promoting the introduction of alternatives into the everyday practice of research.
Abstract: Education is a highly effective way of promoting the introduction of alternatives into the everyday practice of biomedical research and testing. In some countries, specific requirements for the edu...
TL;DR: In this paper, a novel in vitro alternative to in vivo toxicity testing measures the optical response (focal variability) of the cultured bovine lens (obtained from abattoirs) in response to exposure to poten...
Abstract: A novel in vitro alternative to in vivo eye toxicity testing measures the optical response (focal variability) of the cultured bovine lens (obtained from abattoirs) in response to exposure to poten...
TL;DR: The establishment of FRAME in 1969 and the Charity's development during its first 25 years are reviewed, with emphasis on FRAME'S campaigns, FRAME publications, the FRAME Research Programme, theFRAME Toxicity Committee, and FRAME's role in the drafting and passage through Parliament of the Animals (Scientific Procedures) Act 1986.
Abstract: The establishment of FRAME in 1969 and the Charity's development during its first 25 years are reviewed, with emphasis on FRAME'S campaigns, FRAME publications, the FRAME Research Programme, the FRAME Toxicity Committee, and FRAME'S role in the drafting and passage through Parliament of the Animals (Scientific Procedures) Act 1986.
TL;DR: Attention is focused on the moral case and the scientific case against using chimpanzees as laboratory animals, with particular emphasis on research on AIDS.
Abstract: FRAME'S role in drawing attention to the special scientific and ethical concerns raised by the use of non-human primates as laboratory animals is reviewed, with special emphasis on the FRAME/CRAE p...
TL;DR: The generation of epidermal equivalents populated with melanocytes, as well as keratinocytes, makes it possible to study the regulation of melanogenesis, melanocyte–keratinocyte interactions, and how these are affected by UV irradiation.
Abstract: Various three-dimensional human skin models, in which the epidermis exhibits in vivo-like morphological and functional characteristics, have recently been developed. Such models are currently being...
TL;DR: The Jane Goodall Institute has been involved in three workshops with the aim of clarifying the extent to which chimpanzees are seen to be useful in diseases such as hepatitis and AIDS research, with no consensus among scientists regarding their usefulness at the present time.
Abstract: Chimpanzees are more like humans than any other living beings, differing in the composition of their DNA by just over one per cent. There are striking similarities in the anatomy and wiring of the chimpanzee and human brains and central nervous systems. Thus, it should not be surprising to find that there are also striking similarities in the social behaviour, emotional needs and expressions, and cognitive abilities of chimpanzees and humans. These similarities have become increasingly apparent during the last 15 years. Chimpanzees in the wild develop close affectionate bonds between family members that may persist throughout their lifetime of 50 years or more, and examples of true altruism, when individuals protect or even save the lives of non-related companions. Chimpanzees use many objects as tools, and tool-using behaviours differ from place to place across their range. Indeed, there are a number of behaviours that vary between different groups - evidence of cultural traditions passed from one generation to the next through observational learning and imitation. Thus chimpanzees have a very special relationship with humans. A healthy adult chimpanzee is more similar to a healthy adult human in the expression of the intellect than a brain-damaged human, yet in many medical research facilities, chimpanzees are maintained in bleak, bare cages measuring only 5' X 5' X 7'. They may remain in these prisons for life. We do not treat hardened human killers so badly in our society today - there would be a public outcry if we did. I feel strongly that the use of a being so like us, as a human guinea-pig, is not morally justified, and to that end the Jane Goodall Institute has been involved in three workshops with the aim of clarifying the extent to which they are seen to be useful in diseases such as hepatitis and AIDS research. There is no consensus among scientists regarding their usefulness at the present time. If the proposed experiments of transplanting chimpanzee bone marrow tissue into AIDS patients go ahead in the Netherlands, it will be a sad blow for chimpanzee liberation. The attitude of those who believe that any use of non-human primates can be justified provided it results in some benefit, or expected benefit, to humankind, is of precisely the same mind set as that which once allowed us to exploit human beings of another race and use them as slaves. Once we admit that chimpanzees have minds and feelings, are capable of sadness, fear and despair, are able to feel pain, show altruism, and are capable of communicating with each other and with humans in a man-made language, we have to ask serious questions, initially of ourselves, as to whether we should continue to use them in medical research.