SummaryCarbon dioxide (CO 2 ) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO 2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO 2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO 2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO 2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO 2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO 2 as a euthanasia agent.Keywords Carbon dioxide; euthanasia; pain; distress; anaesthesia; welfare; rodents Carbon dioxide (CO 2 ) is commonly used for euthanasia and anaesthesia of laboratory rodents, largely because of its ease of use, relative safety, and low cost, as well as its capacity to euthanize large numbers of animals in a short time span (Ambrose et al. 2000). In large institutions and those with significant rodent-breeding programmes, large numbers of rodents are often euthanized in a short time (Kline et al. 1963) and an appropriate gas agent is often the best way to approach such a challenge. However, CO 2 is not physiologically inert and the published evidence on whether or not CO 2 administration causes pain or distress in animals raises questions about its routine use. This paper reviews this published evidence and includes information on the effects of CO 2 in both humans and nonhumans. Methodological details are included when possible in order to provide a clear
An analysis of primate research in the USA, including the number and species of non-human primates used, types of research, levels of invasiveness, housing conditions and funding, is an important step in addressing various concerns (ethical and scientific) surrounding primate research. An analysis of monkey and chimpanzee research, conducted by The Humane Society of the United States (HSUS), demonstrated that the USA uses more non-human primates (including great apes) in research per year, than any other country in the world. The US government devotes approximately $575–800 million per year to primate research and care. Chimpanzees are most commonly used for hepatitis research; monkeys are most commonly used for HIV research, and other research areas include vaccine and drug testing, cognition, human pathologies/diseases, drug abuse and xenotransplantation. Legislation (including great ape research bans), media attention and proposed increased primate use also contribute to the overall picture of current and future non-human primate research in the USA and throughout the world. The HSUS proposes that cost–benefit analyses of non-human primate research in the USA be conducted to properly assess “value added” to relevant fields of research and whether the use of non-human primates is the only, or most effective, strategy for biomedical progress. Finally, The HSUS proposes a ban on the use of apes in research in the USA and worldwide.
Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal suffering. Further decreases in animal use will stem from international harmonization and coordination of testing programs. Progress in refinement and reduction faces a variety of broad challenges, including limited funding for research. In the specific area of refinement, a key challenge is the issue of distress (as distinct from pain). In the area of reduction, the practice of using unjustifiably high numbers of animals from small species (e.g., rodents) should be challenged. One case study of the use of carbon dioxide as a euthanasia agent illustrates the need for further analysis and research. Notwithstanding the complexities and challenges, the potential for refinement and reduction in regulatory testing is encouraging.
Whether they realize it or not, most stakeholders in the debate about using animals for research agree on the common goal of seeking an end to research that causes animals harm. The central issues in the controversy are about how much effort should be devoted to that goal and when we might reasonably expect to achieve it. Some progress has already been made: The number of animals used for research is about half what it was in the 1970s, and biomedical research has reached the point where we can reasonably begin to envision a time when it could advance without causing harm to animals. With some effort and aggressive development of new biomedical research technologies, full replacement of animals in harmful research is within our grasp. The goal will not be reached all at once, however, and phasing out invasive research on all nonhuman primates should be the priority.
Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.
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