Decompression killing of laboratory rodents: a humane alternative to carbon dioxide?

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Rodents are the most widely used laboratory animals worldwide, and millions of mice and rats are used annually in scientific and medical research. The vast majority of these are killed either during or after the research, and the most common method is to expose them to a rising concentration of carbon dioxide (CO2). However, killing rodents in this way gives rise to important welfare concerns. Studies have shown that CO2 exposure is aversive to rodents because it induces anxiety, breathlessness and above certain concentrations, pain. While researchers have examined different ways of exposing rodents to carbon dioxide with the aim of reducing the welfare impact of this process, there appears to be very limited scope for meaningful refinement. There is an urgent unmet need to identify a humane alternative to this method of killing.Induction of unconsciousness by hypoxia (a deficiency in oxygen reaching body tissues) is considered to be humane in many species, and there is growing interest in the potential of hypobaric hypoxia (a process equivalent to rapidly ascending to high altitude) as a high welfare method of killing. During gradual decompression, animals are rendered unconscious by hypobaric hypoxia as air pressure and therefore oxygen availability is reduced. Although there is evidence that rodents also find hypoxia aversive, this work has been done with inert gases (e.g. Argon) and rapid hypoxia exposure rates. Gradual decompression offers the means to finely control hypobaric hypoxic exposure over variable time periods, improving the likelihood of a humane death. We have encouraging pilot data that suggests that hypobaric hypoxia has the potential to be a method of killing for laboratory rodents that is superior, in welfare terms, to gradual exposure to CO2. The aim of this project is to systematically investigate whether hypobaric hypoxia could be a humane, reliable and efficient method of killing for laboratory rodents.Initially, we will conduct experiments to determine suitable and effective decompression rates for mice and rats, using anaesthetised animals to avoid any welfare harms. We will then work on conscious mice to determine the time to loss of consciousness during exposure to candidate decompression curves and specifically look for signs of pain, anxiety and aversion to the process. These studies will be based on measurement of physiological responses and spontaneous behaviour, and also on a test where we will train mice to use an escape door if they wish to leave an environment that they find aversive. The responses of mice undergoing decompression will be compared to mice exposed to CO2 in the same way as current laboratory practice, to evaluate which (if any) decompression rates are demonstrably more humane. We expect these experiments to clearly show not just the extent of aversion to the different killing methods but to allow us to identify the potential reasons for aversion. If our studies show that hypobaric hypoxia has promise as a humane approach to killing of mice, we will determine an optimal decompression curve, defined as one which causes less pain, anxiety and aversion than gradual exposure to CO2. If our results show that gradual decompression is not better than CO2, the project will provide a definitive answer on hypobaric hypoxia and the results will also provide novel information on the welfare impact of CO2. As a potentially humane alternative, wide adoption of hypobaric hypoxia by the laboratory animal science community would have a profoundly positive effect, enabling millions (and potentially billions) of laboratory animals to be reliably killed with low welfare costs. This outcome would also benefit the operatives whose legal and ethical responsibility it is to kill laboratory animals as humanely as possible. In addition, the killing of laboratory rodents in the most humane way possible will also help to enhance public acceptance of in-vivo animal research.