Striving for humane deaths for laboratory mice: hypobaric hypoxia provides a potential alternative to carbon dioxide exposure

Clarkson, J.M. , Martin, J.E., Sparrey, J., Leach, M.C. and McKeegan, D.E.F. (2023) Striving for humane deaths for laboratory mice: hypobaric hypoxia provides a potential alternative to carbon dioxide exposure. Proceedings of the Royal Society B: Biological Sciences, 290(1997), 20222446. (doi: 10.1098/rspb.2022.2446) (PMID:37122253) (PMCID:PMC10130715)

Abstract

Killing is often an unavoidable and necessary procedure for laboratory mice involved in scientific research, and providing a humane death is vital for public acceptance. Exposure to carbon dioxide (CO2) gas is the most widely used methodology despite well proven welfare concerns. Consequently, the continued use of CO2 and its globally permitted status in legislation and guidelines presents an ethical dilemma for users. We investigated whether killing with hypobaric hypoxia via gradual decompression was associated with better welfare outcomes for killing laboratory mice. We compared the spontaneous behaviour of mice exposed to CO2, decompression or sham conditions, and used analgesic or anxiolytic interventions to determine their relative welfare impact. Gradual decompression resulted in longer times to unconsciousness and death and the pharmacological interventions support the notion of a minimally negative animal experience, while providing further evidence for pain and anxiety associated with exposure to CO2. Decompression resulted in moderate ear haemorrhage, but our welfare assessment suggests this may happen when mice are unconscious. Hence, gradual decompression could be the basis of significant refinement for killing laboratory mice. Future work should corroborate behaviour with neurobiological markers of loss of consciousness to verify the conscious phase of concern for animal welfare.

• Item Type: Articles
• Additional Information: The authors would like to thank the Biotechnology and Biological Sciences Research Council (BBSRC) for funding the research project (grant no. BB/S007210/1). The Roslin Institute was funded by a BBSRC Institute Strategic Program Grant (BB/P013759/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McKeegan, Dr Dorothy and Clarkson, Dr Jasmine and Leach, Dr Matthew and Martin, Miss Jessica

Creator Roles

Clarkson, J.M.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing – original draft, Writing – review and editing
Martin, J.E.: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Writing – review and editing
Leach, M.C.: Conceptualization, Funding acquisition, Investigation, Supervision, Writing – review and editing
McKeegan, D.E.F.: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing

• Authors: Clarkson, J.M., Martin, J.E., Sparrey, J., Leach, M.C., and McKeegan, D.E.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Proceedings of the Royal Society B: Biological Sciences
• Publisher: Royal Society of London
• ISSN: 0962-8452
• ISSN (Online): 1471-2954
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Proceedings of the Royal Society B: Biological Sciences 290(1997): 20222446
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.5525/gla.researchdata.1415

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303692		Decompression killing of laboratory rodents: a humane alternative to carbon dioxide?	Dorothy McKeegan	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/S007210/1	Institute of Biodiversity, Animal Health and Comparative Medicine