NEW DEVELOPMENTS IN BIOSCIENCES: THEIR IMPLICATIONS FOR LABORATORY ANIMAL SCIENCE

New Developments in Biosctences:

Their Implications for Laboratory Animal Science

Proceedings of the Third Symposium of the Federation of European Laboratory Animal Science Associations,

held in Amsterdam, The Netherlands, 1-5 June 1987

edited by

Anton C. Beynen

Department of Laboratory Animal Science, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands

and

Henk A. Solleveld Preclinical Research and Development, Smith Kline & French Laboratories,

Philadelphia, Pennsylvania, U.S.A.

1988

MARTINUS NIJHOFF PUBLISHERS A MEMBER OF THE KLUWER ACADEMIC PUBLISHERS GROUP

DORDRECHT I BOSTON I LANCASTER

Distributors

for the United States and Canada: Kluwer Academic Publishers, P.O. Box 358, Accord Station, Hingham, MA 02018-0358, USA for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon House, Queen Square, Lancaster LA1 1RN, UK for all other countries: Kluwer Academic Publishers Group, Distribution Center, P.O. Box 322, 3300 AH Dordrecht, The Netherlands

Library of Congress Cataloging in Publication Data

Federation of European Laboratory Animal Science Associations. Symposium (3rd 1987, Amsterdam. Netherlands>

New developments In blosclences their Implications for laboratory animal science proceedings of the Third Symposium of the Federation of European Laboratory Animal Science Associations, held In Amsterdam, The Netherlands. 1-5 ~une 1987 I edited by Anton C. Beynen. Henk A. Solleveld.

p. cm. ISBN-13: 978-94-010-7973-0 e-ISBN-13: 978-94-009-3281-4 DOl: 10.1007/978-94-009-3281-4

1. Laboratory anlmals--Congresses. 2. Zoology, Experlmental--Congresses. I. Beynen, Anton C., 1953- II. Solleveld, H. A. III. T1tle. Qi..,55.F43 1987 591' .07·24--dcI9

Copyright

@ 1988 by Martinus Nijhoff Publishers, Dordrecht. Softcover reprint of the hardcover 1st edition 1988

87-28193 CIP

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publishers, Martinus Nijhoff Publishers, P.O. Box 163,3300 AD Dordrecht, The Netherlands.

Preface

This volume includes chapters originally presented at the 3rd FELASA Symposium, held in Amsterdam, June 1-5, 1987. Special topics were "Immune Deficiency Syndromes in Man and Animals", "DNA Technology and Laboratory Animal Science", "Interactions of Behaviour, Housing and Welfare", and "Laboratory Animals as Models in Biomedical Research". In addition, there was a great number of presentations concerning other aspects of laboratory animal science.

We would like to thank the following persons for organizing the Symposium. Mrs. M.A.G. Kuipers, M.Sc., President FELASA Mrs. V. Baumans, D.V.M., Ph.D., Secretary FELASA P. de Vrey, D.V.M., Treasurer Mrs. I. Zaalmink, Organizing and Scientific Secretariat.

The editors would also like to express their gratitude to all the participants and authors for their contribution to this succesful symposium.

A.C. Beynen, Ph.D., Secretary Scientific Committee H.A. Solleveld, Ph.D., Chairman Scientific Committee

FELASA

Federation of European Laboratory Animal Science Associations

Gesellschaft fUr Versuchstierkunde/Society for Laboratory Animal Science Laboratory Animal Science Association

Nederlandse Vereniging voor Proefdierkunde Scandinavian Federation for Laboratory Animal Science

Societe Fran9aise d'Experimentation Animale

v

VII

CONTENTS

Contributors ....................................................... xiii

OPENING ADDRESS: THE FUTURE OF LABORATORY ANIMAL USE R.J. Samsom ....................................................... .

THE ACQUIRED IMMUNEDEFICIENCY SYNDROME IN MAN D.W. van Bekkum .................................................... 7

FELINE ACQUIRED IMMUNODEFICIENCY SYNDROMES M.C. Horzinek ...................................................... 11

IMMUNE DEFICIENCY SYNDROME IN RODENTS: THE NUDE RAT H. van Loveren, H.J. Schuurman and J.G. Vos ........................ 17

ANIMAL WELFARE - COMMON INTEREST M. Luukkainen and E. Hirsjarvi ..................................... 29

LABORATORY ANIMAL ....... SCIENCE - SERVICE - USE K.J. Obrink, M. Waller and L. Wass ................................. 31

LABORATORY ANIMAL SCIENCE IN CZECHOSLOVAKIA P. Kl!r ............................................................ 35

ON THE ETHOLOGY OF PAIN, ITS EXPERIENCE AND EXPRESSION J.A.R.A.M. van Hooff ............................................... 41

PAIN IN NEONATES B.P. Cats.......................................................... 47

ENDORPHINS AND PAIN J .M. van Ree ....................................................... 53

EFFECTS OF EXOGENOUS PAIN RELIEVING SUBSTANCES ON EXPERIMENTAL RESULTS A.M.L. van Delft,.................................................. 59

VETERINARY CARE AT THE PRIMATE CENTER TNO P.M.C.A. van Eerd .................................................. 63

DEVELOPING HOUSING FACILITIES FOR RHESUS MONKEYS: PREVENTION OF ABNORMAL BEHAVIOUR C. Goosen .......................................................... 67

MICROBIOLOGICAL QUALITY ASSURANCE AND QUALITY ASSESSMENT OF LABORATORY ANIMALS R. Boot............................................................ 71

CENTRALISATION - DECENTRALISATION: FAILURE - SUCCESS J.A.P. van Hoof .................................................... 75

VIII

THE EFFECT OF HOMOGENIZATION AND PASTEURIZATION ON THE ALLERGENICITY OF BOVINE MILK ANALYSED BY A MURINE ANAPHYLACTIC SHOCK MODEL O.M. Poulsen and J. Hau ..... ,...................................... 81

MURINE PASSIVE CUTANEOUS ANAPHYLAXIS TEST (PCA) FOR THE "ALL OR NONE" DETERMINATION OF ALLERGENICITY OF BOVINE WHEY PROTEINS AND PEPTIDES O.M. Poulsen and J. Hau ............................................ 87

PHENOTYPIC AND PATHO-MORPHOLOGICAL CHARACTERISTICS IN A HALF-SIB­FAMILY OF TRANSGENIC MICE CARRYING FOREIGN MT-HGH GENES G. Brem and R. Wanke ............................................... 93

THE HOUSING AND HANDLING OF MARMOSETS AND TAMAR INS INFECTED WITH AIDS AND OTHER RETROVIRUSES L. Francis, R.T. Moore, R.T. Raymond and A. Baskerville ............ 99

LONG-TERM OBSERVATION OF LITTER INTERVALS IN PERMANENTLY MONOGAMOUS MATED Han:NMRI MICE K. G. Rapp and R. Kluge ............................................. 105

GENITAL INFLAMMATION IN MALE MICE. A MICROBIOLOGICAL STUDY I. Kunstfr ......................................................... 111

MICROBIAL ASSESSMENT OF A SINGLE FUMIGATION BY FORMALDEHYDE OF A MULTI-LEVEL ANIMAL FACILITY M.R. Gamble and J.R. Needham....................................... 117

MECHANISMS OF NATURAL SELECTION MAINTAINING IN GROUPS OF HIGHLY STANDARDIZED MICE AND RATS, INFLUENCE ON INFECTION RESISTANCE K. Gartner, F. Iglauer, K. Mensing and R. Velleuer ................. 121

PROVOCATION OF LATENT INFECTIONS N.-C. Juhr ..........................•.............................. 127

INTRODUCTION TO RECOMBINANT DNA TECHNOLOGY J. Vijg ....................... ..................................... 133

DNA HYBRIDIZATION AS A TOOL IN DIAGNOSING INFECTIOUS DISEASES. COMPARISON WITH OTHER METHODS. A.D.M.E. Osterhaus................................................. 143

EMBRYO TRANSFER AND MANIPULATION R.L. Gardner....................................................... 147

STRAIN PRESERVATION OF RODENT EMBRYOS. POSSIBILITIES AND LIMITATIONS H.J. Hedrich and I.C. Reetz........................................ 163

THE GENERATION OF TRANSGENIC ANIMALS AND THEIR USE IN FUNDAMENTAL RESEARCH A. Berns ........................................................... 175

ON THE INHERITANCE OF BLOOD CHARACTERS IN MICE R. Kluge, K.G. Rapp and K. Burow................................... 185

INVESTIGATING GENETIC VARIABILITY BETWEEN THE MHS HYPERTENSIVE STRAIN OF RATS AND ITS NORMOTENSIVE CONTROL, MNS B.R. Barber, L. Torielli, M. Ferrandi, P. Ferrari, S. Salardi,

IX

P. Parenti and L. Duzzi ............................................ 191

GENE MAPPING AND LINKAGE HOMOLOGY L.F.M. van Zutphen and M.G.C.W. den Bieman ......................... 197

A NEW METHOD TO PRODUCE ARTIFICIAL MONOZYGOTIC TWINS IN MICE P. Agrawala, E. Baunack and J. Hahn ................................ 203

GENETIC ANALYSIS OF MULTI GENIC TRAITS USING THE RECOMBINANT CONGENIC STRAINS P. Demant, A.A.M. Hart and L.F.M. van Zutphen

ACUTE DERMAL TOXICITY: MORPHOLOGICAL RESPONSE OF THE HAIRLESS MICE SKIN ORGAN CULTURE

209

W. Pitterman, F. Bartnik and K. KUnstler ........................... 215

THE DUTCH RABBIT IN TOXICITY TESTING. CHEMICAL-INDUCED CREATINE KINASE RELEASE; A SPECIES- AND STRAIN-SPECIFIC RESPONSE? T.D. Yih, A.J.M. Degen, J. Kamerman and H.F.P. Joosten

INTERTRIAL-INTERVAL IN THE "WATER ESCAPE TEST" IN MICE

221

H. Heinecke ........................................................ 225

BEHAVIOUR, HOUSING AND WELFARE OF NON-HUMAN PRIMATES T.B. Poole ...................................... _.................. 231

HOUSING AND WELFARE OF LABORATORY RODENTS G. Clough .......................................................... 239

HOUSING CONDITIONS AND EXPERIMENTAL RESULTS W.H. Weihe......................................................... 245

BASIS OF THE EUROPEAN GUIDELINES: FACTS OR lNTUITION? P. de Greeve 255

GNOTOBIOTIC ANIMALS IN NUTRITION RESEARCH B. Ratcliffe....................................................... 267

ANIMAL MODELS FOR CHOLESTEROL METABOLISM STUDIES A.C. Beynen ........................................................ 279

ANIMAL MODELS IN HEMOSTASIS AND THROMBOSIS H.C. Rowsell....................................................... 289

MICE WITH ULCERATING LESIONS ON THE NOSE, LIMBS AND/OR TAIL H. van Herck and V. Baumans ........................................ 295

SPONTANEOUS HYPERPLASIA OF THE ENDOMETRIUM IN THE RABBIT P. Zwart ........................................................... 299

x

MONKEY GRAFFITY: ENVIRONMENTAL DEFICIENCY, BOREDOM OR ARTISTIC DRIVE? D. Wesseling, V. Baumans and C. Goosen............................. 305

MARKING OF AFRICAN CLAWED TOADS (Xenopus laevis). IMPROVEMENT OF A SKIN AUTOGRAFT TECHNIQUE J.A. Loopstra, P. Zwart, R. Verhoeff-de Fremery and F.J.M. Vervoordeldonk ..................................................... 311

CHANGES IN ENERGY INTAKE, BODY WEIGHT GAINS, AVERAGE FEED EFFICIENCY AND SOME PLASMA HORMONE LEVELS IN DOGS FROM DIFFERENT ENVIRONMENTS G. Kuhn and W. Hardegg ...................................... ~...... 317

SERUM CONCENTRATIONS OF VITAMINS A, D AND E OF GROWING BEAGLES FED COMMERCIAL DOG AND FOX DIETS H.-M. Voipio, T. Nevalainen and P. Maenpaa

INTEGRATION OF HGH GENE IN TRANSGENIC MICE AND TRANSMISSION TO NEXT GENERATION

325

B. Brenig and G. Brem .............................................. 331

ATTEMPTS TO PRODUCE TRANSGENIC RABBITS CARRYING MTI-HGH RECOMBINANT GENE K. Ross, B. Brenig, J. Meyer and G. Brem ........................... 337

ELECTROFUSION OF EARLY MAMMALIAN EMBRYO CELLS A. Clement, J. Meyer and G. Brem ................................... 343

PASSIVE INFRARED MOVEMENT DETECTOR, A NEW EQUIPME~T TO MONITOR MOTOR ACTIVITY OF SMALL RODENTS IN NORMAL CAGES H. Sigg and P. Tamborini ........................................... 349

ESTABLISHMENT OF A SPF POPULATION OF Cricetulus griseus U. Marki, W. Rossbach and J. Leuenberger ........................... 353

CHRONIC PHLORIZIN INTOXICATION IN ADIPOSE MUTANT MICE C57BL/KS db/db AND IN NORMAL CONTROLS I. Ortlepp, K. Gartner, H. Sch5tz and A. Zogbaum ................... 359

PLASMA a-AMYLASE AND LIPASE ACTIVITIES IN DOGS WITH VARIATIONS IN FOOD COMPOSITION AND AVAILABILITY G. Kuhn and W. Hardegg ............................................. 365

LOCOMOTOR ACTIVITY OF A BEHAVIOR MUTANT IN NMRI MICE C. Heckl-Ensslin and I. von Butler ................................. 373

THE APPLICATION OF EMBRYO TRANSFER AND CRYOPRESERVATION TO COMMERCIAL LABORATORY ANIMAL BREEDING F. Dagmes-Hansen ................................................... 375

SEROLOGICAL FOLLOWING OF A LABORATORY RAT BREEDING CONTAMINATED WITH RESPIRATORY VIRUSES DURING 1981 - 1986 M. Pribylova, T. Svoboda and P. Klir ............................... 379

ERADICATION OF ENCEPHALITOZOONOSIS IN RABBIT BREEDING COLONIES BY CARBON IMMUNOASSAY

XI

T. Waller .......................................................... 385

SPONTANEOUS MURINE HEMOSIDEROSIS, A MODEL FOR HUMAN HEMOCHROMATOSIS? T.S. Veninga and H. Morse.......................................... 389

IN VITRO ADHESION OF K88 POSITIVE E. COLI TO INTESTINAL VILLI OF JUST-WEANED PIGLETS E. Cox, V. Cools and A. Houvenaghel ................................ 393

THE EFFECTS OF GENTLING ON OPEN-FIELD BEHAVIOUR OF RATS P.A. Hirsj~rvi and M.A. Junnila .................................... 399

BLASTOMERE-KARYOTYPING: A DIRECT METHOD FOR PRODUCING MOUSE TRISOMY 16~DIPLOID AGGREGATION CHIMERAS AS AN ANIMAL MODEL OF HUMAN DOWN'S SYNDROME C. Bacchus and W. Buselmaier ....................................... 405

A PROPOSED SPECIES DIFFERENCE IN THE RENAL EXCRETION OF PERFLUORO OCTANOIC ACID IN THE BEAGLE DOG AND RAT H. Hanhij~rvi, M. Ylinen, T. Haaranen and T. NevalaLlen

MEASUREMENT OF ORTHOSTATIC RESPONSES IN CONSCIOUS DOGS E. Ahonen, T. Nevalainen, E. L~nsimies, K. Tahvanainen,

409

J. Hartikainen and M. Hakum~ki ..................................... 413

ORAL 65Zn LOADING TEST IN RATS FED IRI-OB DIET WITH VARIOUS Zn CONCENTRATIONS J.P. van Wouwe, M. Veldhuizen and C.J.A. van den Hamer ............. 419

MORTALITY AND TUMOUR INCIDENCE OF BDII/HAN RATS J. Kaspareit-Rittinghausen and F. Deerberg ......................... 425

ASSESSMENT OF DISCOMFORT INDUCED BY ORBITAL HiHCTURE IN RATS A.C. Beynen, V. Baumans, J.W.M. Haas, K.K. van Hellemond, F.R. Stafleu and G. van Tintelen ........................................ 431

EFFECT OF MORPHINOMIMETICS IN DIFFERENT PAIN TESTS K.M. Dhasmana, A.K. Banerjee and W. Rating ......................... 437

PREVENTION OF EARLY DEATHS IN MICE CONTAMINATED WITH GRAM NEGATIVE ENTERIC BACTERIA AND FUNGUS FOLLOWING IRRADIATION A.K. Banerjee, A.F. Angulo and J. Kong-A-San ....................... 443

DETECTION OF Mycoplasma neurolyticum IN A COLONY OF INBRED MICE: CLINICALLY SILENT INFECTION A.F. Angulo, A.K. Banerjee and A.A. Polak-Vogelzang 447

EFFECTS OF HANDLING AND TRANSPORTATION STRESS ON RODENTS M. Landi, T. Bowman and S. Campbell................................ 449

CONTRIBUTORS*

P. Agrawala, Abteilung fUr experimentelle Fortpflanzungsbiologie, Klinik fUr Gyn~kologie des Rindes, Tier~rtzlichen Hochschule Hannover, Hannover, Federal Republic of Germany (203)

E. Ahonen, Department of Clinical Physiology, Kuopio University Central Hospital, SF-70210 Kuopio, Finland (413)

A.F. Angulo, National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (443, 447)

C. Bacchus, Institut fUr Humangenetik und Anthropologie, Universitat Heidelberg, 1m Neuenheimer Feld 328, D-6900 Heidelberg, Federal Republic of Germany (405)

A.K. Banerjee, Laboratory Animal Centre, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands (437, 443, 447)

B.R. Barber, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

F. Bartnik, Henkel KGaA, Postfach 1100, D-4000 DUsseldorf 1, Federal Republic of Germany (215)

A. Baskerville, PHLS, Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire, SP4 OJG, United Kingdom (99)

V. Baumans, Department of Laboratory Animal Science, Veterinary Faculty, State University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands (295, 305, 431)

XIII

E. Baunack, Zentrales Tierlaboratorium, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strasse 8, D-3000 Hannover 61, Federal Republic of Germany (203)

D.W. van Bekkum, Radiobiological Institute TNO, P.O. Box 5815, 2280 HV Rijswijk, The Netherlands (7)

A. Berns, Division of Molecular Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam and Department of Biochemistry, University of Amsterdam, Amsterdam, The Netherlands (175)

A.C. Beynen, Department of Laboratory Animal Science, Veterinary Faculty, University of Utrecht, P.O. Box 80.166, 3508 TD Utrecht and Department of Human Nutrition, Agricultural University, De Dreijen 12, 6703 BC Wageningen, The Netherlands (279, 431)

M.G.C.W. den Bieman, Department of Laboratory Animal Science, Veterinary Faculty, University of Utrecht, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands (197)

R. Boot, National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (71)

*The number in parentheses is the opening page number of the contributor's article.

XIV

T. Bowman, Smith Kline and French Laboratories, 709 Swedeland Road L620, Swedeland, PA 19479, U.S.A. (449)

G. Brem, Institut fur Tierzucht und Tierhygiene, Ludwig-Maximilians-Universitat, Veterinarstrasse 13, D-8000 Munchen 22, Federal Republic of Germany (93, 331, 337, 343)

B. Brenig, Institut fur Tierzucht und Tierhygiene, Ludwig-Maximilians-Universitat, Veterinarstrasse 13, D-8000 Munchen 22, Federal Republic of Germany (331, 337)

K. Burow, Kali-Chemie Pharma GmbH, Hans-Bockler-Allee 20, 3000 Hannover, Federal Republic of Germany (185)

W. Buselmaier, Institut fur Humangenetik und Anthropologie, Universitat Heidelberg, 1m Neuenheimer Feld 328, D-6900 Heidelberg, Federal Republic of Germany (405)

I. von Butler, Institut fur Tierzucht der technischen Universitat MUnchen, D-8050 Freising-Weihenstephan, Federal Republic of Germany (373)

S. Campbell, Smith Kline and French Laboratories, 709 Swedeland Road L620, Swedeland, PA 19479, U.S.A. (449)

B.P. Cats, Wilhelmina Children's Hospital, P.O. Box 18009, 3501 CA Utrecht, The Netherlands (47)

A. Clement, Institut fur Tierzucht und Tierhygiene, Ludwig-Maximilians-Universitat, Veterinarstrasse 13, D-8000 Munchen 22, Federal Republic of Germany (343)

G. Clough, Alanann Consultancy Services, P.O. Box 230, York, YOI IGG, United Kingdom (239)

V. Cools, Laboratory of Veterinary Physiology, State University Centre of Antwerp, Slachthuislaan 68, 2008 Antwerp, Belgium (393)

E. Cox, Laboratory of Veterinary Physiology, State University Centre of Antwerp, Slachthuislaan 68, 2008 Antwerp, Belgium (393)

F. Dagnres-Hansen, Bomholtgaard Breeding and Research Center Ltd., Bomholtvej 10, DK-8680 Ry, Denmark (375)

F. Deerberg, Central Institute for Laboratory Animal Breeding, Hermann-Ehlers-Allee 57, D-3000 Hannover 91, Federal Republic of Germany (425)

A.J.M. Degen, Organon International B.V., Drug Safety Research and Development Laboratories, P.O. Box 20, 5340 BH Oss, The Netherlands (221)

A.M.L. van Delft, Scientific Development Group, Organon International B.V., P.O. Box 20, 5340 BH Oss, The Netherlands (59)

P. Demant, The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (209)

K.M. Dhasmana, Department of Anaesthesiology, Medical Faculty, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands (437)

L. Duzzi, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

P.M.C.A. van Eerd, Primate Center TNO, P.O. Box 5815, 2280 HV Rijswijk, The Netherlands (63)

M. Ferrandi, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

P. Ferrari, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

L. Francis, PHLS, Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire, SP4 OJG, United Kingdom (99)

M.R. Gamble, The Boots Company PLC, Research Department, Nottingham, NG2 3AA, United Kingdom (117)

R.L. Gardner, Imperial Cancer Research Fund, Developmental Biology Unit, Department of Zoology, South Parks Road, Oxford, OXI 3PS, United Kingdom (147)

K. Gartner, Medizinische Hochschule Hannover, Zentrales Tierlaboratorium, Konstanty-Gutschow-Strasse 8, D-3000 Hannover 61, Federal Republic of Germany (121, 359)

C. Goosen, Primate Center TNO, P.O. Box 5815, 2280 HV Rijswijk, The Netherlands (67, 305)

P. de Greeve, Veterinary Public Health Inspectorate, Section Animal Experimentation, P.O. Box 5406, 2280 HK Rijswijk, The Netherlands (255)

T. Haaranen, National Laboratory Animal Center, University of Kuopio, P.O. Box 6, 70211 Kuopio, Finland (409)

J.W.M. Haas, Small Animal Center, Agricultural University, De Dreijen 12, 6703 BC Wageningen, The Netherlands (431)

J. Hahn, Abteilung fUr experimentelle Fortpflanzungsbiologie, Klinik fUr Gynakologie des Rindes, Tierartzlichen Hochschule Hannover, Hannover, Federal Republic of Germany (203)

M. Hakumaki, Department of Physiology, University of Kuopio, SF-70211 Kuopio, Finland (413)

C.J.A. van den Hamer, Department of Radiochemistry, Interuniversity Reactor Institute, Mekelweg 15, 2629 JB Delft, The Netherlands (419)

H. Hanhijarvi, Oy Star Ab Pharmaceutical Co., P.O. Box 33, 33721 Tampere, Finland (409)

xv

W. Hardegg, Institut fUr Versuchstierkunde der Universitat Heidelberg, 1m Neuenheimer Feld 347, D-6900 Heidelberg, Federal Republic of Germany (317, 365)

XVI

A.A.M. Hart, The Netherlands Cancer Institute, Antoni van Leeuwen­hoekhuis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (209)

J. Hartikainen, Department of Physiology, University of Kuopio, SF-70211 Kuopio, Finland (413)

J. Hau, Department of Pathology, Laboratory Animal Unit, Royal Veterinary and Agricultural University, Copenhagen, Denmark (81, 87)

C. Heckl-Ensslin, Institut fur Tierzucht der technischen Universitat Munchen, D-8050 Freising-Weihenstephan, Federal Republic of Germany (373)

H.J. Hedrich, Zentralinstitut fur Versuchstierzucht, Hermann-Ehlers-Allee 57, D-3000 Hannover 91, Federal Republic of Germany (163)

H. Heinecke, Central Institute of Microbiology and Experimental Therapy, Academy of Sciences of the GDR, Beutenbergstrasse 11, DDR-6900 Jena, German Democratic Republic (225)

K.K. van Hellemond, Small Animal Center, Agricultural University, De Dreijen 12, 6703 Be Wageningen, The Netherlands (431)

H. van Herck, Division of Laboratory and Special Animal Diseases, Department of Veterinary Pathology and Department of Laboratory Animal Science, State University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands (295)

E. Hirsjarvi, Central Finlands Association for Laboratory Animal Welfare, Tikantie 23, 40520 Jyvaskyla, Finland (29)

P.A. Hirsjarvi, Department of Applied Zoology, University of Kuopio, P.O. Box 6, 70211 Kuopio, Finland (399)

J.A.P. van Hoof, Vakgroep Bestuur en Beleid, P.O. Box 9108, 6500 HK Nijmegen, The Netherlands (75)

J.A.R.A.M. van Hooff, Laboratory of Comparative Physiology, Jan van Galenstraat 40, 3572 LA Utrecht, The Netherlands (41)

M.C. Horzinek, Institute of Virology, Veterinary Faculty, State University, P.O. Box 80.164, 3508 TD Utrecht, The Netherlands (11)

A. Houvenaghel, Laboratory of Veterinary Physiology, State University Centre of Antwerp, Slachthuislaan 68, 2008 Antwerp, Belgium (393)

F. Iglauer, Medizinische Hochschule Hannover, Zentrales Tierlaboratorium, Konstanty-Gutschow-Strasse 8, D-3000 Hannover 61, Federal Republic of Germany (121)

H.F.P. Joosten, Organon International B.V., Drug Safety Research and Development Laboratories, P.O. Box 20, 5340 BH Oss, The Netherlands (221)

N.-C. Juhr, Institut fur Versuchstierkunde und Versuchstierkrankheiten, Freie Universitat Berlin, Krahmerstrasse 6, D-1000 Berlin 45, Federal Republic of Germany (127)

M.A. Junnila, Institute of Occupational Health, Helsinki, Finland (399)

J. Kamerman, Organon International B.V., Drug Safety Research and Development Laboratories, P.O. Box 20, 5340 BH Oss, The Netherlands (221)

J. Kaspareit-Rittinghausen, Central Institute for Laboratory Animal Breeding, Hermann-Ehlers-Allee 57, D-3000 Hannover 91, Federal Republic of Germany (425)

P. Kl{r, Institute of Physiology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia (35, 379)

R. Kluge, Abteilung fur Versuchstierkunde des Klinikums der RWTH Aachen, Pauwelsstrasse, D-5100 Aachen, Federal Republic of Germany (105, 185)

J. Kong-A-San, Laboratory Animal Centre, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands (443)

G. Kuhn, Institut fUr Versuchstierkunde der Universitat Heidelberg, 1m Neuenheimer Feld 347, D-6900 Heidelberg, Federal Republic of Germany (317, 365)

K. Kunstler, Henkel KGaA, Postfach 1100, D-4000 Dusseldorf 1, Federal Republic of Germany (215)

XVII

I. Kunstyr, Medizinische Hochschule Hannover, Institut fur Versuchstierkunde, Postfach 610180, D-3000 Hannover, Federal Republic of Germany (111)

M. Landi, Smith Kline and French Laboratories, 709 Swedeland Road L620, Swedeland, PA 19479, U.S.A. (449)

E. Lansimies, Department of Clinical Physiology, Kuopio University Central Hospital, SF-70210 Kuopio, Finland (413)

J. Leuenberger, Institut fur biologisch medizinische Forschung AG, W5lferstrasse 4, CH-4414 FUllinsdorf, Switzerland (353)

J.A. Loopstra, Division of Laboratory and Special Animal Diseases, Department of Veterinary Pathology, State University, Yalelaan 1, 3584 CL Utrecht, The Netherlands (311)

H. van Loveren, Laboratory for Pathology, National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (17)

M. Luukkainen, Central Finlands Association for Laboratory Animal Welfare, Tikantie 23, 40520 Jyvaskyla, Finland (29)

P. Maenpaa, Department of Biochemistry, University of Kuopio, Finland (325 )

U. Marki, Institut fUr biologisch medizinische Forschung AG, W5lferstrasse 4, CH-4414 FUllinsdorf, Switzerland (353)

XVIII

K. Mensing, Medizinische Hochschule Hannover, Zentrales Tierlaboratorium, Konstanty-Gutschow-Strasse 8, D-3000 Hannover 61, Federal Republic of Germany (121)

J. Meyer, Institut fUr Tierzucht und Tierhygiene, Ludwig-Maximilians­Universit!t, Veterin!rstrasse 13, D-8000 MUnchen 22, Federal Republic of Germany (337, 343)

R.T. Moore, PHLS, Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire, SP4 OJG, United Kingdom (99)

H. Morse, Hope Farms B.V., P.O. Box 85, 3440 AB Woerden, The Netherlands (389)

J.R. Needham, The Microbiology Laboratories, 56 Northumberland Road, North Harrow, Middlesex, United Kingdom (117)

T. Nevalainen, National Laboratory Animal Center, University of Kuopio, Savilahdentie 11 M, 70210 Kuopio, Finland (325, 409, 413)

K.J. Obrink, Institute of Physiology, Uppsala University, Biomedical Center, Box 572, S-75123 Uppsala, Sweden (31)

I. Ortlepp, Abteilung fUr Labortierkunde, Universit!t ZUrich, Winterthurerstrasse 190, CH-8057 ZUrich, Switzerland (359)

A.D.M.E. Osterhaus, The National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (143 )

P. Parenti, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

W. Pitterman, Henkel KgaA, Postfach 1100, D-4000 DUsseldorf 1, Federal Republic of Germany (215)

A.A. Polak-Vogelzang, National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (447)

T.B. Poole, Universities Federation for Animal Welfare, 8 Hamilton Close, South Mimms, Potters Bar, Herts EN6 3QD, United Kingdom (231)

O.M. Poulsen, Institute of Obstetrics and Gynaecology, University of Odense, Denmark (81, 87)

M. Pribylova, Institute of Physiology, Czechoslovak Academy of Sciences, Videnska 1083, 14220 Prague, Czechoslovakia (379)

K.G. Rapp, Zentralinstitut fUr Versuchstierzucht, Hermann-Ehlers-Allee 57, D-3000 Hannover 91, Federal Republic of Germany (105, 185)

B. Ratcliffe, Polytechnic of North London, Holloway Road, London, N7 8DB, United Kingdom (267)

W. Rating, Department of Anaesthesiology, Medical Faculty, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands (437)

R.T. Raymond, FHLS, Centre for Applied Microbiology and Research, Forton Down, Salisbury, Wiltshire, SF4 OJG, United Kingdom (99)

J.M. van Ree, Rudolf Magnus Institute for Fharmacology, State University, Vondellaan 6, 3521 GD Utrecht, The Netherlands (53)

I.C. Reetz, Zentralinstitut fUr Versuchstierzucht, Hermann-Ehlers-Al1ee 57, D-3000 Hannover 91, Federal Republic of Germany (163)

K. Ross, Institut fUr Tierzucht und Tierhygiene, Ludwig-Maximilians­Universitat, Veterinarstrasse 13, D-8000 MUnchen 22, Federal Republic of Germany (337)

W. Rossbach, Institut fUr biologisch medizinische Forschuug AG, WBlferstrasse 4, CH-4414 FUllinsdorf, Switzerland (353)

H.C. Rowsell, Canadian Council for Animal Care, 1105-151 Slater Street, Ottawa, Ontario, KIF 5H3, Canada (289)

S. Salardi, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

R.J. Samsom, Director-in-Chief of Health Frotection Branche, Ministry of Welfare, Health and Cultural Affairs, Rijswijk, The Netherlands (1)

H. SchBtz, Abteilung fUr Labortierkunde, Universitat ZUrich, Winterthurerstrasse 190, CH-8057 ZUrich, Switzerland (359)

H.J. Schuurman, Division of Immunopathology, Department of Internal Medicine and Fathology, University Hospital, Catharijnesingel 101, 3511 GV Utrecht, The Netherlands (17)

H. Sigg, Nestle Research Center, Nestec Ltd., Vers-chez-Ies-Blanc, 1000 Lausanne 26, Switzerland (349)

F.R. Stafleu, Department of Laboratory Animal Science, State University, F.O. Box 80.166, 3508 TD Utrecht, The Netherlands (431)

T. Svoboda, Institute of Fhysiology, Czechoslovak Academy of Sciences, Videnska 1083, 14220 Frague, Czechoslovakia (379)

K. Tahvanainen, Department of Clinical Fhysiology, Kuopio University Central Hospital, SF-70210 Kuopio, Finland (413)

F. Tamborini, Institut fUr Toxico1ogie, ETH und Universitat ZUrich, 8603 Schwerzenbach, Switzerland (349)

XIX

G. van Tintelen, Small Animal Center, Agricultural University, De Dreijen 12, 6703 BC Wageningen, The Netherlands (431)

L. Torielli, Farmitalia Carlo Erba, Istituto Ricerche Nerviano, Milano, Italy (191)

M. Veldhuizen, Department of Radiochemistry, Interuniversity Reactor Institute, Mekelweg 15, 2629 JB Delft, The Netherlands (419)

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R. Velleuer, Medizinische Hochschule Hannover, Zentrales Tierlaboratorium, Konstanty-Gutschow-Strasse 8, D-3000 Hannover 61, Federal Republic of Germany (121)

T.S. Veninga, Department of Radiopathology, State University of Groningen, Bloemsingel 1, 9713 BZ Groningen, The Netherlands (389)

R. Verhoeff - de Fremery, Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands (311)

F.J.M. Vervoordeldonk, Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands (311)

J. Vijg, TNO Institute for Experimental Gerontology, P.O. Box 5815, 2280 HV Rijswijk, The Netherlands (133)

H.-M. Voipio, National Laboratory Animal Center, University of Kuopio, Savilahdentie 11 M, 70210 Kuopio, Finland (325)

J.G. Vos, Laboratory for Pathology, National Institute of Public Health and Environmental Hygiene, P.O. Box 1, 3720 BA Bilthoven, The Netherlands (17)

M. Waller, Uppsala Biomedical Center, Box 570, S-75123 Uppsala, Sweden (31)

T. Waller, Pharmacia AB, 75182 Uppsala, Sweden (385)

R. Wanke, Institut fur Tierpathologie, Ludwig-Maximilians-Universitat, Veterinarstrasse 13, D-8000 MUnchen 22, Federal Republic of Germany (93)

L. Wass, National Board of Universities and Colleges, Box 45501, 10~30

Stockholm, Sweden (31)

W.H. Weihe, Biologisches Zentrallaboratorium, Universitatsspital, Universitat Zurich, Ramistrasse 100, 8091 Zurich, Switzerland (245)

D. Wesseling, Department of Laboratory Animal Science, Veterinary Faculty, State University, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands (305)

J.P. van Wouwe, Department of Pediatrics, University Hospital Leiden, P.O. Box 9600, 2300 RC Leiden and Department of Radiochemistry, Interuniversity Reactor Institute, Mekelweg 15, 2629 JB Delft, The Netherlands (419)

T.D. Yih, Organon International B.V., Drug Safety Research and Develop­ment Laboratories, P.O. Box 20, 5340 BH Oss, The Netherlands (221)

M. Ylinen, National Laboratory Animal Center, University of Kuopio, P.O. Box 6, 70211 Kuopio, Finland (409)

A. Zogbaum, Abteilung fur Labortierkunde, Universitat Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland (359)

L.F.M. van Zutphen, Department of Laboratory Animal Science, Veterinary Faculty, University of Utrecht, P.O. Box 80.166, 3508 TD Utrecht, The Netherlands (197, 209)

P. Zwart, Division of Laboratory and Special Animal Diseases, Department of Veterinary Pathology, University of Utrecht, Yalelaan 1, 3584 CL Utrecht, The Netherlands (299, 311)

XXI