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Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change.

ABSTRACT: Evidence indicates that carbon dioxide (CO₂) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement over CO₂ but are not widely adopted. We conducted an online survey of Canadian and European laboratory animal professionals and researchers (n = 592) to assess their attitudes towards the use of CO₂ and alternative methods for rodent euthanasia using quantitative 7-point scale (from 1 (= strongly oppose) to 7 (= strongly favour) and qualitative (open-ended text) responses. CO₂ was identified as the most common method used to kill rodents, and attitudes towards this method were variable and on average ambivalent (mean ± SD score on our 7-point scale was 4.4 ± 1.46). Qualitative analysis revealed four themes relating to participant attitude: (a) the animal's experience during gas exposure; (b) practical considerations for humans; (c) compromise between the animal's experience and practical considerations; and (d) technical description of the procedure or policies. Many participants (51%) felt that there were alternatives available that could be considered an improvement over CO₂, but perceived barriers to implementing these refinements. Qualitative analysis of these responses revealed five themes: (a) financial constraints; (b) institutional culture; (c) regulatory constraints; (d) research constraints; and (e) safety concerns. In conclusion, concerns regarding the use of CO₂ often focused on the animal's experience, but barriers to alternatives related to operational limitations. New research is now required on to how best to overcome these barriers.

SUBMITTER: Brunt MW

PROVIDER: S-EPMC8669199 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing rodents according to the Directive 2010/63/EU. Within the scope of refinement, our aim was to investigate if isoflurane and sevoflurane are an appropriate alternative killing method to CO2 in mice. Different concentrations of CO2 (filling rates of 20%, 60%, 100%; CO2 20, 60, 100), isoflurane (Iso 2%, 5%) and sevoflurane (Sevo 4.8%, 8%) were compared in two mouse strains (NMRI, C57Bl/6J) using a broad spectrum of behavioral parameters, including the approach-avoidance test, and analyzing blood for stress parameters (glucose, adrenaline, noradrenaline). We focused in our study on the period from the beginning of the gas inlet to loss of consciousness, as during this period animals are able to perceive pain and distress. Our results show that only higher concentrations of CO2 (CO2 60, 100) and isoflurane (5%) induced surgical tolerance within 300 s in both strains, with CO2 100 being the fastest acting inhalant anesthetic. The potency of halogenated ethers depended on the mouse strain, with C57Bl/6J being more susceptible than NMRI mice. Behavioral analysis revealed no specific signs of distress, e. g. stress-induced grooming, and pain, i. e. audible vocalizations, for all inhalant gases. However, adrenaline and noradrenaline plasma concentrations were increased, especially in NMRI mice exposed to CO2 in high concentrations, whereas we did not observe such increase in animals exposed to isoflurane or sevoflurane. Escape latencies in the approach-avoidance test using C57Bl/6J mice did not differ between the three inhalant gases, however, some animals became recumbent during isoflurane and sevoflurane but not during CO2 exposure. The rise in catecholamine concentrations suggests that CO2 exposure might be linked to a higher stress response compared to isoflurane and sevoflurane exposure, although we did not observe a behavioral correlate for that. Follow-up studies investigating other fast-acting stress hormones and central anxiety circuits are needed to confirm our findings.

Project description:Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss of consciousness; time to loss of consciousness; best methods for use of CO2; and the availability of better alternatives. These discussions have been useful in providing new information, but have resulted in significant confusion regarding the acceptability of CO2 for rodent euthanasia. In some cases, researchers and veterinarians have become uncertain as to which techniques to recommend or use for euthanasia of laboratory mice and rats. Methods: The International Association of Colleges of Laboratory Animal Medicine (IACLAM) convened a taskforce to examine the evidence for adverse welfare indicators in laboratory rats and mice undergoing CO2 euthanasia using a SYRCLE-registered systematic review protocol. Of 3,772 papers identified through a database search (PubMed, Web of Science, CAB Direct, Agricola, and grey literature) from 1900 to 2017, 37 studies were identified for detailed review (some including more than one species or age group), including 15 in adult mice, 21 in adult rats, and 5 in neonates of both species. Experiments or reports were excluded if they only assessed parameters other than those directly affecting animal welfare during CO2 induction and/or euthanasia. Results: Study design and outcome measures were highly variable and there was an unclear to high risk of bias in many of the published studies. Changes in the outcome measures evaluated were inconsistent or poorly differentiated. It is likely that repeated exposures to carbon dioxide inhalation are aversive to adult rats and mice, based on avoidance behavior studies; however, this effect is largely indistinguishable from aversion induced by repeated exposures to other inhalant anesthetic gasses. Conclusion: There is insufficient evidence to permit an unbiased assessment of the effect of CO2 inhalation during euthanasia on welfare indicators in laboratory mice and rats. Additional well-designed, unbiased, and adequately powered studies are needed to accurately assess the welfare of laboratory mice and rats undergoing euthanasia via CO2 gas.

Project description:OBJECTIVES:Prospective registration of animal studies has been suggested as a new measure to increase value and reduce waste in biomedical research. We sought to further explore and quantify animal researchers' attitudes and preferences regarding animal study registries (ASRs). DESIGN:Cross-sectional online survey. SETTING AND PARTICIPANTS:We conducted a survey with three different samples representing animal researchers: i) corresponding authors from journals with high Eigenfactor, ii) a random Pubmed sample and iii) members of the CAMARADES network. MAIN OUTCOME MEASURES:Perceived level of importance of different aspects of publication bias, the effect of ASRs on different aspects of research as well as the importance of different research types for being registered. RESULTS:The survey yielded responses from 413 animal researchers (response rate 7%). The respondents indicated, that some aspects of ASRs can increase administrative burden but could be outweighed by other aspects decreasing this burden. Animal researchers found it more important to register studies that involved animal species with higher levels of cognitive capabilities. The time frame for making registry entries publicly available revealed a strong heterogeneity among respondents, with the largest proportion voting for "access only after consent by the principal investigator" and the second largest proportion voting for "access immediately after registration". CONCLUSIONS:The fact that the more senior and experienced animal researchers participating in this survey clearly indicated the practical importance of publication bias and the importance of ASRs underscores the problem awareness across animal researchers and the willingness to actively engage in study registration if effective safeguards for the potential weaknesses of ASRs are put into place. To overcome the first-mover dilemma international consensus statements on how to deal with prospective registration of animal studies might be necessary for all relevant stakeholder groups including animal researchers, academic institutions, private companies, funders, regulatory agencies, and journals.

Project description:BackgroundReducing the number of animals used in experiments has become a priority for the governments of many countries. For these reductions to occur, animal-free alternatives must be made more available and, crucially, must be embraced by researchers.MethodsWe conducted an international online survey for academics in the field of animal science (N?=?367) to explore researchers' attitudes towards the implementation of animal-free innovations. Through this survey, we address three key questions. The first question is whether scientists who use animals in their research consider governmental goals for animal-free innovations achievable and whether they would support such goals. Secondly, responders were asked to rank the importance of ten roadblocks that could hamper the implementation of animal-free innovations. Finally, responders were asked whether they would migrate (either themselves or their research) if increased animal research regulations in their country of residence restricted their research.ResultsWhile nearly half (40%) of the responders support governmental goals, the majority (71%) of researchers did not consider such goals achievable in their field within the near future. In terms of roadblocks for implementation of animal-free methods, ~?80% of the responders considered 'reliability' as important, making it the most highly ranked roadblock. However, all other roadblocks were reported by most responders as somewhat important, suggesting that they must also be considered when addressing animal-free innovations. Importantly, a majority reported that they would consider migration to another country in response to a restrictive animal research policy. Thus, governments must consider the risk of researchers migrating to other institutes, states or countries, leading to a 'brain-drain' if policies are too strict or suitable animal-free alternatives are not available.ConclusionOur findings suggest that development and implementation of animal-free innovations are hampered by multiple factors. We outline three pillars concerning education, governmental influence and data sharing, the implementation of which may help to overcome these roadblocks to animal-free innovations.

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Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change.

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