Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Wilson-Welder, J. H., Frank, A. T. 2021. Use of food enrichment for medication delivery in large groups of sheep. Laboratory Animal Science Professional 9(3) (May/June), 40-43.

In a 2018 AALAS webinar on Sheep and Goat Analgesia, Dr. Susie Vogel, a small ruminant expert, introduced the concept of getting sheep and goats to willingly take medication by putting it in a tasty...

Dalla Costa, F. A., Gibson, T. J., Oliveira, S. E.O. et al. 2021. On-farm culling methods used for pigs. Animal Welfare 30(4), 507-522.

The culling of injured and non-viable pigs (Sus scrofa) (neonate to breeding stock) is a routine and necessary procedure on most farms. Usually, pigs are culled using one of the following methods: blunt-force trauma (manual...

Kay, W. R., Mawson, P. R. 2021. An efficient method for the euthanasia of cane toads (Rhinella marina) under northern Australian field conditions. Animals 11(8), 2239.

The euthanasia of cane toads under field conditions presents a number of logistical and animal welfare challenges. One recommended method of control involves the use of carbon dioxide in plastic bags. This paper describes the...

Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

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...

Edwards, S. (Ed.) 2021. Understanding the behaviour and improving the welfare of pigs. Burleigh Dodds Science Publishing Limited, Sawston, Cambridge, UK. 594 p.

With growing concern from consumers and regulatory agencies about the welfare of farmed animals such as pigs, the livestock sector must assess how animal welfare can be improved whilst ensuring livestock production remains economically and...

Çavuşoğlu, E., Rault, J.-L., Gates, R. et al. 2020. Behavioral response of weaned pigs during gas euthanasia with CO2, CO2 with butorphanol, or nitrous oxide. Animals 10(5), 787.

The swine industry is often forced to euthanize pigs in the first few weeks of life due to injuries, hernias, or unthriftiness. The majority of pigs are euthanized using carbon dioxide (CO2) gas asphyxiation but...

Millecam, J., van Bergen, T., Devreese, M. 2020. Gastrostomy tube placement via a laparotomic procedure in growing conventional piglets to perform multidose preclinical paediatric drug studies. Laboratory Animals 54(3), 261-271.

The use of juvenile conventional pigs as a preclinical animal model to perform pharmacokinetic (PK), pharmacodynamic (PD) and safety studies for the paediatric population is increasing. Repetitive oral administration of drugs to juvenile pigs is...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

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...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...

Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.

Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...

Laferriere, C. A., Leung, V. S., Pang, D. S. 2020. Evaluating intrahepatic and intraperitoneal sodium pentobarbital or ethanol for mouse euthanasia. JAALAS 59(3), 264–268.

Intraperitoneal (IP) injection of sodium pentobarbital (PB) is an accepted method of euthanasia for mice. However, this method has important drawbacks, including the potential for pain or misinjection. The objective of this prospective, randomized, blinded...

Galex, I. A., Gallant, C. M., D'Avignon, N. et al. 2020. Evaluation of effective and practical euthanasia methods for larval African clawed frogs (Xenopus laevis). JAALAS 59(3), 269–274.

Larval, or tadpole-stage Xenopus laevis frogs are a popular research model for developmental biology and disease studies. Existing euthanasia guidance documents offer recommendations for both eggs and adult stages, yet do not specifically address the...

Natusch, D. J. D., Aust, P. W., Khadiejah, S. et al. 2020. Behavioral and corticosterone responses to carbon dioxide exposure in reptiles. PLOS ONE 15(10), e0240176.

The use of carbon dioxide (CO2) exposure as a means of animal euthanasia has received considerable attention in mammals and birds but remains virtually untested in reptiles. We measured the behavioral responses of four squamate...

Rault, J.-L., Lai, A., Hemsworth, L. et al. 2020. Wireless ‘under the skull’ epidural EEG and behavior in piglets during nitrous oxide or carbon dioxide gas euthanasia. Physiology & Behavior 227, 113142.

Consciousness is central to animal welfare concerns. Its assessment is most often conducted based on behavior, with a poor understanding of the correspondence between behavior and the neurobiological processes that underlie the subjective experience of...

Arruda, A. G., Beyene, T. J., Kieffer, J. et al. 2020. A systematic literature review on depopulation methods for swine. Animals 10(11), 2161.

Swine mass depopulation refers to the destruction of large numbers of pigs and may include not only animals affected with a disease but also healthy pigs in a facility or surrounding areas. Emerging applications of...

Atkinson, S., Algers, B., Pallisera, J. et al. 2020. Animal welfare and meat quality assessment in gas stunning during commercial slaughter of pigs using hypercapnic-hypoxia (20% CO2 2% O2) compared to acute hypercapnia (90% CO2 in Air). Animals 10(12), 2440.

This study assessed aversion, stunning effectiveness, and product quality of nitrogen and carbon dioxide (CO2) mixtures used for stunning pigs. A total of 1852 slaughter pigs divided into two similar batches was assessed during routine...

Lindahl, C., Sindhøj, E., Brattlund Hellgren, R. et al. 2020. Responses of pigs to stunning with nitrogen filled high-expansion foam. Animals 10(12), 2210.

Nitrogen gas (N2) delivered in high expansion foam in a closed container could be a feasible method for humanely stunning pigs. This study aimed to evaluate potential aversion in pigs to the N2 foam method...

Scarborough, J., Mueller, F., Arban, R. et al. 2020. Preclinical validation of the micropipette-guided drug administration (MDA) method in the maternal immune activation model of neurodevelopmental disorders. Brain, Behavior, and Immunity 88, 461-470.

Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages...

Woodard, C. L., Nasrallah, W. B., Samiei, B. V. et al. 2020. PiDose: An open-source system for accurate and automated oral drug administration to group-housed mice. Scientific Reports 10, 11584.

Drug treatment studies in laboratory mice typically employ manual administration methods such as injection or gavage, which can be time-consuming to perform over long periods and cause substantial stress in animals. These stress responses may...

Stanger, K. J., Kells, N. J., Fisher, A. D. et al. 2019. Evaluation of euthanasia of sheep with intravenous saturated salt solutions to enable the collection of whole, intact brains. Animal Welfare 28(4), 397-406.

Captive bolts or firearms are unsuitable for euthanasia of livestock when an intact brain is required for diagnostics. Injectable barbiturates can be used, but this method carries risk of poisoning animals eating the carcase. Intravenous...

Bouwsema, J. A., Lines, J. A. 2019. Could low atmospheric pressure stunning (LAPS) be suitable for pig slaughter? A review of available information. Animal Welfare 28(4), 421-432.

Low atmospheric pressure stunning (LAPS) is a slaughter technique which may be less stressful for pigs (Sus scrofa domestica) than current commercial stunning and slaughter methods. The main methods used currently for slaughtering pigs are...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...