Alternative Methods in Toxicology

Volume 11 - The World Congress on Alternatives and Animal Use in the Life Sciences: Education, Research, Testing

Series Editor: ALAN M. GOLDBERG, L.F.M. van ZUTPHEN
Mary Ann Liebert, Inc. | Publishers

TABLE OF CONTENTS

Preface

Acknowledgements

Contributing Authors

Part One: Plenary Lectures

• Replacement Alternatives and the Concept of Alternatives
  A.J. Rowan
• The History of Animal Use in the Life Sciences
  J. Parascandola
• The Role of Animals and Alternatives in Education
  R.T. Fosse
• Science, Ethics, and Animals
  F.S. Carney
• The Need to Redefine Animal Care and Use
  D.B. Morton
• Reduction of Animal Use and Experimental Design
  M.F.W. Festing
• Alternatives in Safety Testing: Progress or Uselessness?
  M. Roberfroid
• Animals and Society
  A.M. Beck
• The Development of Legislation on the Use of Animals and Alternatives
  G. Pechovitch

Part Two: Special Presentations

• W.M.S. Russell Speech at the Awards Luncheon
  W.M.S. Russell
• Picard's Dilemma (Text of the play presented at the World Congress banquet
  Deborah Rudacille

Part Three: In Vitro Studies

• Heavy Metals
  1. Organotypic Slice Cultures as In Vitro Model for Studying Long-Term Effects of Neurotoxic and Convulsant Substances in the Brain
     B.H. Gahwiler, M. Muller, C. Fortunato, R. Durr, P. Streit, and S.M. Thompson
  2. Neural Cell Cultures as Model Systems to Identify and Assess Mechanisms of Neurotoxicity
     G.J. Harry
  3. Assessing Developmental Neurotoxicity to Psychomotor Stimulants
     A.D. Weissman
  4. Mechanisms of Nitric Oxide Neurotoxicity in Primary Neuronal Cultures
     V.L. Dawson and T.M. Dawson
  5. A Tissue Culture Model of Serotonin Neurons for Studying Normal Development and Screening for Drug Teratogenicity
     P.M. Whitaler-Azmitia and E.C. Azmitia
• Reproductive Toxicity
  1. The Use of Rat Embryo Culture in Reproductive Toxicity Testing
     W.S. Webster
  2. Exposure of Drosophila Embryonic Cells to a 60Hz Sinusoidal Magnetic Field: Effect on Teratogenesis and Heat Shock Protein 70 Expression
     N. Bournias-Vardiabasis, P. Nguyen, and J.L. Phillips
  3. Inhibition of Hyperactivated Motility of Rabbit Spermatozoa by Metals
     R.J. Young
  4. Use of Bursal Lymphocytes to Assess the Genetic Effects of Phenoxyherbicides in Chick Embryos
     E. Arias
• Hepatic Function and Metabolism
  1. An Overview of In Vitro Liver Models
     A. Guillouzo, S. Langouet, and O. Fardel
  2. Cultured Human Hepatocytes for Drug Hepatoxicity Research
     J.V. Castell, M.J. Gomez-Lechon, R. Trullenque, and R. Fabra
  3. Mammalaian Cell Lines Genetically Engineered for Metabolic Competence
     J. Doehmer
  4. Apical and Basolateral Gentamicin Exposure Result in Temporally Distinct Electrophysiological Alterations in Cultured Human Proximal Tubule Cells
     J.H. Todd, D.A. Sens, and M.A. Sens
  5. Use of Human Liver Slices and Hepatocytes in Transport and Metabolism Studies
     P. Olinga, M.T. Merema, G.W. Sandker, M.J.H. Slooff, D.K.F. Meijer, and G.M.M. Groothius
  6. The Usage of Cytochrome P450 Database (CPD) for Prediction of the Drugs' Fate in Living Systems
     A.I. Archakov and G.I. Bachmanova
  7. New Approaches for the Preservation of Metabolic Zonation in Rat Hepatocyte Cultures
     P. Maier, B. Saad, and K. Ohno
• Biologicals
  1. Reduction, Replacement, and Refinement of Animal Tests Used in the Control of Bacterial Vaccines - Progress, Prospects, and Possibilities
     P.A. Knight
  2. Transgenic Mice Carrying Human Poliovirus Receptor Gene as Animal Model to Study Poliovirus Pathogenesis
     A. Nomoto
  3. Determination of Erysipelas Antibodies by an Enzyme Immunoassay: A Method to Replace the Mouse Protection Test Required for Potency Testing of Bacterins
     K. Cussler, R. Beckmann, and R. Weiss
  4. Simple and Quick Measurement of Radiosensitivity of Cells by Cytokinesis Block Micronucleus Assay - Special Reference to Alpha Value or Response to 1-3 Gy
     K. Ono, S. Masunaga, M. Akaboshi, and E.O. Wandl
  5. In Vitro Production of Monoclonal Antibodies in High Concentration in a New and Easy to Handle Modular Minifermenter
     H. Weichert, F.W. Falkenberg, M. Krane, I. Bartels, H.-O. Nagels, and H. Fiebig
  6. High Performance Receptor Binding Chromatography (HPRBC) for Human Growth Hormone (hGH)
     J.E. Battersby, E. Conova-Davis, A.C. Celniker, B.C. Cunningham, B.L. Fletcher, R.L. Garnick, R.L. Gehant, E.R. Hoff, G. Hunt, P.A. McKay, J.V. O'Connor, K.C. Olsen, D.K. Parikh, E.C. Roswall, G.M. Teshima, J.A. Wells, and M.E. Winkler
• Toxicity Testing
  1. The Fixed Dose Procedure as an Alternative to the Classical LD50 Test: Acceptance by the EEC and OECD
     R.J. Fielder
  2. The MEIC Program and Its Implications for the Prediction of Acute Human Systemic Toxicity
     E. Walum, M. Nilsson, C. Clemedson, and B. Ekwall
  3. Quantitative Methods of Detecting Cytokine mRNA and Protein Changes in Lymphocytes as an Alternative to Acute Toxicity Testing in Animals
     B. Markovic, G. Malich, and C. Winder
  4. Nuclear Receptors and the Development of Alternative Tests
     A.A. Levin and J.F. Grippo
• Dermal Toxicology
  1. The Development of In Vitro Tests for Skin Corrosion and Irritation
     P.A. Botham
  2. Differences Between Immediate and Delayed Phototoxicity: The Concept of the Battery of Two In Vitro Phototoxicty Tests
     D.T. Sladowski, S.J. Steer, B.M. Sladowska, R.H. Clothier, and M. Balls
  3. Human Skin Organ Culture as an Alternative to Animal Model to Study the Allergenicity of Low Molecular Weight Chemical Compounds/Haptens
     A. Rambukkana, F.H.M. Pistoor, D. Irik, W. Menko, J.D. Bos, M.L. Kaspsenberg, and P.K. Das
  4. Prospective and Predictive Testing for Delayed Contact Hypersensitivity in Laboratory Animals and Man
     E.V. Buehler
• Ocular
  1. Relevance and Reliability of In Vitro Methods and Ocular Safety Assessment
     M. Cottin, K.G. dossou, O. de Silva, M. Tolle, R. Roguet, C. Cohen, P. Catroux, I. Delabarre, C. Sicard, and A. Rougier
  2. The Draize Eye Test and Progress in Development and Acceptance of Alternatives to This Test in Europe
     E. Schlede and I. Gerner
• Renal Toxicology
  1. Failure of Wilms' Tumor Blastema to Differentiate Under Conditions Which Promote the Growth of Fetal Proximal Tubule Cells from the Human Fetal Kidney
     D.A. Sens, A.J. Garvin, D.J. Hazen-Martin, G.G. Re, and M.A. Sens
  2. Foscarnet-Induced Toxicity of Human Renal Prozimal Tubule Cells
     A.L. Trifillis, X. Cui, and G.L. Drusano

Part Four: Risk Assessment and Extrapolation

• Alternatives and Risk Assessment: A Risk Worth Taking
  M.J. van den Heuvel
• The Chicken Enucleated Eye Test (CEET): A Screen for the Assessment of Eye Irritation/Corrosion Potential of Compounds
  M.K. Prinsen
• Alternatives in Safety Testing: Approaches in the Slovak Republic
  M. Vargova
• Combining In Vitro Alternatives and Physiologically-Based Computer Modeling Will Improve Quantitative Health Risk-Assessments
  M.E. Andersen
• Structure-Activity Relationships as Alternatives in the Study of Carcinogenesis
  H.S. Rosenkranz and G. Klopman
• Attempts to Validate a Possible Predictive Animal Model for Human Erythrocyte G-6-PD Deficiency
  E.J. Calabrese, H.M. Horton, and T. Gentile
• Rat as a Model to Study Postprandial Effects in Man
  J. Ritskes-Hoitinga, K.H. van het Hof, W.J. Kloots, E.A.M. de Deckere, J.M.M. van Amelsvoort, and J.A. Westrate

Part Five: Validation

• Validation Programs in Europe
  B.J. Blaauboer and M. Balls
• Observations on US Validation Studies
  R.A. Scala
• Validation of New Toxicology Test Systems - The Paradigm of Genetic Toxicity Tests
  E. Zeiger
• Current Status of Validation Studies in Japan
  H. Ono

Part Six: Databases

• The Landscape of Alternatives - AWIC
  J.A. Larson
• The UC Center for Animal Alternatives
  L.A. Hart and D.C. Anderson
• The Status of In Vitro Toxicity Testing Databases in Europe
  K. Ungar
• Public Sources of In Vitro Toxicity Testing Data in North America
  M.R. Green
• The Galileo Data Bank of Alternative Methodologies to the Use of Animals in Toxicity Testing
  G. Loprieno, G. Boncristiani, E. Bosco, N. Loprieno, and M. NIeri

Part Seven: Pharmacopeial

• Reduction of the Use of Animals for Quality Control Testing in the European Pharmacopoeia
  J.-M. Spieser
• USP Alternatives to Animal Testing: The In Vitro Option - A Progress Report
  L.T. Grady and R. Dabbah

Part Eight: Education and Training

• Education - The Three R's Concept
  1. Education as a Contribution to the Introduction of Alternatives in Research and Testing
     L.F.M. van Zutphen and A.C. Beynen
  2. An Assessment of Educational Requirements and Training Strategies in North America
     G.L. Van Hoosier, Jr., C.A. Pekpw, M.B. Dennis, Jr., and C.S. Scott
  3. Search for Alternatives to Animal Use in Medical Education - Tempus Joint European Project
     Z. Cervinkova, M. Cervinka, M. Balls, and H. Spielmann
  4. Continuing Education and Training (CET) - A Vital Part of Use of Laboratory Animals and Alternatives in Education, Research, and Testing
     R.P. Maickel, M.A. Suckow, and L.A. Terril-Robb
• Computers in Education
  1. Rapid Information Exchange - Networking Biomedical Researchers Via the Internet and Other Computer Connections
     K. Boschert
  2. Using Computer Networks in Distance Learning: Professional and Public Education
     D.C. Ferguson and P.D. Pion
  3. Painless Protein, A Computer-Interative Learning Environment
     S. Dubin and K. McKee
  4. The Virtual Clinic (TM), A Virtual Reality Surgical Simulator
     K.T. McGovern and L.T. McGovern
  5. Interactive Video (Multimedia) in Animal Techniques Training (A Cost Effective Alternative to Using Animals)
     M. Connelly
  6. Evaluation of Interactive Learning Materials
     J. Moonen
  7. Experiences with Computers in Veterinary Education
     A. Smith
  8. Simulated Animal Preparations in Pharmacology Teaching
     H. van Wilgenburg
  9. Computer Simulations of Animal Experiments in Undergraduate Teaching - Use and Evaluation
     D.G. Dewhurst

Part Nine: Animal Welfare Issues

• On the Ethical and Scientific Need for Assessing the Potential Benefit of Research Likely to Cause Suffering to Protected Animals
  M. Balls
• Mechanisms of Pain
  G.F. Gebhart
• Euthanasia
  1. Euthanasia: The Assessment of Welfare and Scientific Aspects
     N.G. Gregory
  2. The Ethics of Death as an Endpoint: Euthanasia as an Alternative
     J. Tannenbaum
• Environmental Manipulations to Promote Psychological Well-Being in Primates
  P. Theran
• Animal Boredom: Consequences for Housing and Feeding Conditions
  F. Wemelsfelder
• Refinement of Perioperative Care
  P. Flecknell
• Refining Anaesthetic Techniques in a Laboratory Animal Facility: Practical Problems
  V. Baumans and H. van Herck
• Pain and Distress in Laboratory Animals: What We Know and What We Assume
  P.F. Brain
• Preclinical Models for Analgesic Drug Study
  T.L. Yaksh

Part Ten: Ethical Aspects

• Ethical Scoring Systems
  D.P. Boisvert and D.G. Porter
• The Austrailian and New Zealand Council for the Care of Animals in Research and Teacing
  R.M. Baker
• The Role of Animal Care Committees in Fostering Use of Alternatives: A Case Study
  A.D. Bowd
• The Use of Rabbits, Dogs, Cats, and Primates in USDA-Registered and Federal Biomedical Laboratories in the United States 1975-1992
  C.H. Lingeman, L. Krulisch, and L. Tockey
• The Psychology of Animal Rights Activism
  H. Herzog
• The Caring Sleuth: A Qualitative Analysis of Animal Rights Activists
  K. Shapiro
• Public Attitudes Toward Animal Research: A Comparative Study of 15 Nations
  L. Pifer and K. Shimizu

Part Eleven: Barriers to the Acceptance of Alternatives

• On Recognizing and Overcoming Barriers to the Acceptance of Alternative Methods
  M. Balls and J.H. Fentem
• Progress in the Acceptance of In Vitro Tests by Regulatory Authorities
  R.J. Fielder
• The Erosion of Acceptability of Animal Toxicity Tests in the Courtroom
  H.E. Hazard

Part Twelve: Funding Sources

• Directory of Funding Sources for Scientific Pursuit of Alternatives
  A. Tarzi and F.B. Orlans

Part Thirteen: Point of View

• Endpoints and Cell Systems for In Vitro Toxicity Assessments: A Discussion of Specific Target Cell Toxicity Versus Basal Cytotoxicity
  1. Lethality: In Vitro and In Vivo
     O. Flint
  2. The Basal Cytotoxicity Concept
     B. Ekwall
• In Vitro and In Vivo Alternative or Complementary Techniques?
  S. Garattini

Appendix