GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES THE ASSESSMENT AND ALLEVIATION OF PAIN AND DISTRESS IN RESEARCH ANIMALS: WORKING TO BUILD A HEALTHY AUSTRALIA GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES THE ASSESSMENT AND ALLEVIATION OF PAIN AND DISTRESS IN RESEARCH ANIMALS [This publication is a living document and will be updated from time to time. Please refer to the NHMRC website at http://www.nhmrc.gov.au/index.htm to download updates for incorporation into this folder.] © Australian Government 2008 Paper-based publication This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced by any process without written permission from the Commonwealth available from the Attorney-General’s Department. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney-General’s Department, Robert Garran Offices, National Circuit, Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca ISBN 1 864 96360 3 (print) © Australian Government 2008 Electronic documents This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use, or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests for further authorisation should be directed to the Commonwealth Copyright Administration, Attorney-General’s Department, Robert Garran Offices, National Circuit, Canberra, ACT, 2600 or posted at: http://www.ag.gov.au/cca ISBN 1 864 96366 2 (online) Published May 2008 Prepared by the Expert Working Group of the Animal Welfare Committee of the National Health and Medical Research Council To obtain details regarding NHMRC publications, contact: Email: [email protected] Phone: Toll free 13 000 NHMRC (13 000 64672) or call 02 6217 9000 Internet: http://www.nhmrc.gov.au Contents CONTENTS HOW TO USE THIS DOCUMENT vii DEFINITIONS ix ABBREVIATIONS xi PART I ANIMAL WELLBEING AND SCIENTIFIC OUTCOMES 1 General principles for using animals in scientific activities 3 2 Wellbeing, stress, distress and pain 5 3 Effects of an animal’s wellbeing on scientific outcomes 13 PART II PLANNING, CONDUCTING AND REVIEWING RESEARCH PROTOCOLS TO MAXIMISE WELLBEING AND MINIMISE PAIN AND DISTRESS IN ANIMALS 4 Planning new research protocols 17 5 Gaining approval for new research protocols 43 6 Implementing and reviewing strategies to promote wellbeing 45 7 Checklist for promoting animal wellbeing 49 PART III FACTSHEETS A Administration of substances A1 B Behaviour modification B1 C Biological sample collection C1 D Blood collection D1 E Environmental enrichment strategies E1 F Foetal and embryonic studies F1 G Food and water intake modification G1 H Humane killing and euthanasia H1 I Pain management: anaesthesia, analgesia and anxiolytics I1 J Polyclonal antibody production J1 K Surgical procedures K1 L Toxicology L1 M Tumour induction M1 N Wildlife research N1 APPENDIX: PROCESS REPORT Process Report 1 INDEX Index 1 GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES | iii Contents TABLES Table 4.1 Likelihood and consequence matrix for characterising risk 27 Table 4.2 Species-specific signs of pain and/or distress 37 Table A1 Common methods and routes of intravenous administration of substances A3 Table A2 Recommended maximum injectable volumes for laboratory rabbits and rodents A4 Table A3 Recommended needle gauge (G) and length for different species of animal A4 Table A4 Procedures to minimise pain and distress when administering substances A9 Table B1 Procedures for minimising pain and distress when modifying behaviour B5 Table C1 Summary table for urine collection methods and their performance C6 Table D1 Recommended site and volume of blood collection using calculated blood volume D2 Table D2 Maximum volumes and recovery periods for blood collection D4 Table D3 Signs and treatment of acute blood loss D5 Table D4 Wellbeing issues to consider for blood collection in selected species D7 Table E1 Environmental enrichment strategies for animal species used in scientific research E2 Table G1 Procedures and points to consider when restricting the diet of animals used in scientific research G6 Table H1 Methods of humane killing and euthanasia in rats and mice H4 Table H2 Methods of humane killing and euthanasia in guinea pigs H4 Table H3 Methods of humane killing and euthanasia in rabbits H5 Table H4 Methods of humane killing and euthanasia in sheep and goats H5 Table H5 Methods of humane killing and euthanasia in birds H6 Table H6 Methods of humane killing and euthanasia in pigs H6 Table H7 Methods of humane killing and euthanasia in fish H7 Table I1 Inhalation anaesthesia: induction and maintenance concentrations of inhalation anaesthetics in laboratory animals I15 Table I2 Injectable anaesthesia in rodents and rabbits I15 Table I3 Injectable anaesthesia in other laboratory animals I17 Table I4 Analgesia in rodents and rabbits: non-steroidal anti-inflammatory drugs (NSAIDs) I18 Table I5 Analgesia in rodents and rabbits: opioids I19 Table I6 Analgesia in other laboratory animals: non-steroidal anti-inflammatory drugs (NSAIDs) I20 Table I7 Analgesia in other laboratory animals: opioids I21 Table J1 Maximum volumes for injection of antigen with depot adjuvant for different animal species J4 Table K1 Minimising surgical risks to animal wellbeing K10 iv | GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES Contents FIGURES Figure 2.1 Schematic diagram of wellbeing 5 Figure 2.2 Model of stress and distress response 8 Figure 2.3 Nerve pathways involved in perception of, and response to, pain 10 Figure 4.1 Early planning for a project that might involve the use of animals 18 Figure I1 Example of pain management options classified according to the potential for the procedure to result in pain and distress (‘invasiveness’) I3 Figure I2 Site of action of analgesic agents in the pain pathway I13 GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES | v How to use this document HOW TO USE THIS DOCUMENT These guidelines are to be read in conjunction with the Australian code of practice for the care and use of animals for scientific purposes (the Code). The guidelines promote the wellbeing of animals used for scientific purposes, and aim to minimise their experience of pain and distress. To do this, the guidelines are divided into three parts. • Part I provides background material to assist understanding and awareness of animal wellbeing and how it relates to scientific activities. • Part II provides basic strategies for – planning research protocols to identify the risk of animal pain and distress – conducting research to manage the risk of animal pain and distress – reviewing research protocols to minimise animal pain and distress in future research. • Part III provides factsheets on issues to consider for specific research protocols. They have been developed with the aim of providing guidance to investigators, rather than being prescriptive. Please consult the Code for principles governing the use of animals for scientific purposes. The online version of this document can be found at http://www.nhmrc.gov.au The information in this document will be regularly reviewed, so please consult the above website for updates. If you have any feedback or would like to notify us of updates, please contact us at: [email protected] GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES | vii Definitions DEFINITIONS These definitions have been taken from the Code and have been selected as the most relevant to these guidelines. See the Code for other definitions. Animal welfare An animal’s quality of life based on an assessment of an animal’s physical and psychological state as an indication of how the animal is coping with the ongoing situation as well as a judgement about how the animal feels (see also ‘Animal wellbeing’ and ‘Distress’). Animal wellbeing An animal’s present state with regard to its relationship with all aspects of its environment, both internal and external. It implies a positive mental state, successful biological function, positive experiences and freedom from adverse conditions. Distress The state of an animal that has been unable to adapt completely to stressors, and that manifests as abnormal physiological or behavioural responses. It can be acute or chronic and may result in pathological conditions. Distress is associated with negative emotional experiences and can be caused by either physical or psychological stressors, or both. Euthanasia The humane killing of an animal, in the interests of its own welfare, to alleviate pain and distress (see ‘Humane killing’). Humane killing The process of killing an animal with minimal pain and distress (see ‘Euthanasia’). Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage. It may elicit protective actions, result in learned avoidance and distress and may modify species-specific traits of behaviour, including social behaviour. GUIDELINES TO PROMOTE THE WELLBEING OF ANIMALS USED FOR SCIENTIFIC PURPOSES | ix Abbreviations ABBREVIATIONS 3Rs the principles of Replacement, Reduction and Refinement AEC animal ethics committee CSF cerebrospinal fluid DNA deoxyribonucleic acid ECG electrocardiograph ELISA enzyme-linked immunosorbent