i Principles of Laboratory Animal Science Revised Edition ii A heading iii Principles of Laboratory Animal Science A contribution to the humane use and care of animals and to the quality of experimental results REVISED EDITION Edited by L.F.M. van Zutphen V. Baumans A.C. Beynen 2001 ELSEVIER AMSTERDAM • LONDON • NEW YORK • OXFORD • PARIS • SHANNON • TOKYO iv ELSEVIER SCIENCE B.V. Sara Burgerhartstraat 25 P.O. Box 211, 1000 AE Amsterdam, The Netherlands © 2001 Elsevier Science B.V. All rights reserved This work and the individual contributions contained in it are protected under copyright by Elsevier Science B.V., and the following terms and conditions apply to its use: Photocopying Single photocopies of single chapters may be made for personal use as allowed by national copyright laws. 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Second (revised) edition 2001 British Library Cataloguing in Publication Data Principles of laboratory animal science : a contribution to the humane use and care of animals and to the quality of experimental results. – Rev. ed. 1. Animal experimentation 2. Laboratory animals 3. Animal welfare I. Zutphen, L. F. M. van II. Baumans, V. (Vera) III. Beynen, Anton C. 590.7’24 ISBN 0444506128 Library of Congress Cataloging in Publication Data A catalog record from the Library of Congress has been applied for. ISBN: 0-444-50612-8 ∞ The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Printed in The Netherlands. v Preface It is widely recognized now that education and training in laboratory animal science are essential both for the quality of research and for the welfare of animals. Scientists who are responsible for the design and conduct of animal ex- periments must not only be educated in one of the biomedical sciences (biol- ogy, medicine, veterinary medicine, pharmacy, etc.), but should also have taken an introductory course in laboratory animal science, encompassing welfare issues, ethical aspects and animal alternatives. Indeed, in some coun- tries such requirements have been made compulsory by law. This book contains basic facts and principles covering the main theoretical aspects of such a course. More than 50 authors, all experts in their fields have contributed relevant topics for the graduate student or young scientist who wishes to become a “competent” researcher. After a general introduction (chap- ter 1) and a glimpse into legislation (chapter 2), information is presented on the biology and husbandry of the most frequently used animal species (chap- ter 3) and on the relationship between behaviour, stress and wellbeing (chap- ter 4). Standardization can contribute to a reduction of animal use and several aspects are covered in chapters 5–8. Chapter 9 deals with procedures for the diagnosis of diseases in laboratory animals and the consequences brought about by impaired health on both the welfare of the animals and the results of the experiments. Chapters 10–13 outline several factors that should be taken into account when designing and conducting animal experiments. Persons involved in animal experimentation must be able to recognize signals of pain and distress (chapter 14). The researcher must also have some basic knowl- edge of anaesthesia (chapter 15) particularly when invasive techniques are part of the experiment (chapter 16). The book concludes by outlining the possibilities and limitations of the use of alternatives (chapter 17), together with a chapter on the ethical aspects of animal experimentation (chapter 18). v vi Preface For further reading, a list of recommended literature is given at the end of each chapter. It should be emphasized that the completion of a biomedical training pro- gramme that includes a course in laboratory animal science, may provide a basis for a humane and responsible use of animals, but does certainly not provide full competence. The great diversity of biomedical disciplines and the wide range of animal experiments performed by scientists, working in the field of biomedical science, implies that a standard training programme in which every requirement for the various kinds of animal experiments is fully met, is not feasible. There is no substitute for learning in the field, and a close co-operation with conscientious and experienced investigators, animal care- takers and animal technicians remains essential in order to fill any gaps in skill and knowledge. The second edition of this book is largely the same as the previous edition. Also the list of contributors is only slightly changed. We would like to thank Dr. A.P.M.G. Bertens, Prof. Dr. W.J.I. van der Gulden, Dr. P.G.C. Hermans, Dr. B.C. Kruijt, Prof. Dr. E. Lagerweij, Dr. G.W. Meijer, Dr. J.W.M.A. Mullink (†), Prof. Dr. K.J. Öbrink (†) and Dr. G.A. van Oortmerssen for their contri- bution to the first edition and are grateful to Dr. A.E.J.M. van den Bogaard, Dr. H.A. van Lith, Prof. Dr. R. Remie and Dr. J.B.F. van der Valk for their willingness to contribute to this second edition. We have prepared this second edition as careful as possible but would welcome critique and suggestions for further improvements. The editors A heading vii Contributors Prof.dr. M. Balls European Centre for the Validation of Alternative Methods (ECVAM), IRC Institute for Health and Consumer Protection, 21020 Ispra (VA), Italy Dr. V. Baumans Department of Laboratory Animal Science, Utrecht University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands Dr. R.G.M. ten Berg The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Prof. dr. ir. A.C. Beynen Department of Laboratory Animal Science, Utrecht University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands Dr. H.J.M. Blom Department of Laboratory Animal Science, Utrecht University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands Dr. A.E.J.M. van den Bogaard Centralised Experimental Animal Facility, P.O. Box 616, 6200 MD Maas- tricht, The Netherlands Prof. dr. L.H.D.J. Booij Institute for Anesthesiology, University of Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands Drs. R. Boot National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The Netherlands vii viii Contributors Dr. M.C. Bosland Institute of Environmental Medicine, New York University Medical Center, Long Meadow Road, Tuxedo, N.Y. 10987, U.S.A. Prof. dr. P.F. Brain School of Biological Sciences, University of Wales, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom Dr. M. Coates Shepperlands Farm, Finchampstead, Workingham RG40 4QF, United Kingdom Prof. dr. Tj. de Cock Buning Department of Laboratory Animal Issues, Utrecht University, Yalelaan 17, 3584 CL Utrecht, The Netherlands Prof. dr. J.E. van Dijk Department of Veterinary Pathology, Utrecht University, P.O. Box 80158, 3508 TD Utrecht, The Netherlands Dr. M.F.W. Festing M.R.C. Toxicology Unit, P.O. Box 138, Lancaster Rd., Leicester LE1 9HN, United Kingdom Prof. dr. P.A. Flecknell Comparative Biology Centre, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom Dr. R.T. Fosse LASW, Aventis Pharma, Building H840 – Room 144, Industriepark Höchst, 65926 Frankfurt am Main, Germany Prof. dr. K. Gärtner Institute for Laboratory Animal Science, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany Drs. P.C.M. de Greeve Ministry of Public Health, Inspectorate W&V, P.O. Box 16.108, 2500BC ’s Gravenhage, The Netherlands Prof.