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. 
Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Neely, C., Lane, C., Torres, J. et al. 2018. The effect of gentle handling on depressive-like behavior in adult male mice: Considerations for human and rodent interactions in the laboratory. Behavioural Neurology 2018, 2976014.

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being...

Champneys, T., Castaldo, G., Consuegra, S., et al. 2018. Density dependent changes in neophobia and stress-coping styles in the world’s oldest farmed fish. Royal Society Open Science 5(12), 181473.

Farmed fish are typically reared at densities much higher than those observed in the wild, but to what extent crowding results in abnormal behaviours that can impact welfare and stress coping styles is subject to...

O’Rourke, D. P., Baccanale, C. L., Stoskopf, M. K. 2018. Nontraditional laboratory animal species (cephalopods, fish, amphibians, reptiles, and birds). ILAR Journal 59(2), 168-176.

Aquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

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...

Larsen, R. A., Peveler, J. L., Klutzke, J. B. et al. 2017. Effects of daily restraint with and without injections on skeletal properties in C57BL/6NHsd mice. Lab Animal 46(7), 299-301.

Studies typically involve groups of animals that are injected with placebo compounds. As there are studies that demonstrate that restraint and injection can affect behavior and corticosteroid levels in rodents, the basis of such placebo...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...

Boivin, G. P., Bottomley, M. A., Schiml, P. A. et al. 2017. Physiologic, behavioral, and histologic responses to various euthanasia methods in C57BL/6NTac male mice. JAALAS 56(1), 69-78.

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as...

Waters, J. 2017. Time for change? Practicalities of implementing non-aversive methods for handling mice. Animal Technology and Welfare 16(1), 47-56.

Recent studies have shown that the method choice for handling laboratory mice is important to animal welfare. In 2015, 60% of all animals used in Home Office procedures were laboratory mice. Given the large number...

Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...

Tucker, R. D. 2017. Woodchuck College. Laboratory Animal Science Professional 5(2) (June), 33-36.

Marmota monax is a valuable laboratory animal species used in studies of Hepatitis B virus (HBV), food intake, obesity, hibernation, and circannual cycles. This article describes the woodchuck’s (also known as groundhog) natural behavior and...

Valentim, A. M., Guedes, S. R., Pereira, A. M. et al. 2016. Euthanasia using gaseous agents in laboratory rodents. Laboratory Animals 50(4), 241-253.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously...

Powell, K., Ethun, K., Taylor, D. K. 2016. The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. Lab Animal 45(10), 386-395.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility...

Hawkins, P., Prescott, M., Carbone, L. et al. 2016. A good death? Report of the second Newcastle meeting on laboratory animal euthanasia. Animals 6(9), 50.

Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus...

Sánchez-Muros, M. J., Sánchez, B., Barroso, F. G. et al. 2016. Effects of culture densities on feed demand, behavioural tests and on the hepatic and cerebral oxidative status in tilapia (Oreochromis sp.). Applied Animal Behaviour Science 185, 137-145.

The present study examines whether fish density affects behavioural tests, feed demand, and different parameters indicative of the oxidative status of the liver and brain of Orechromis sp. to identify welfare indicators for fish culturing...

Loberg, J. M., Lundmark, F. 2016. The effect of space on behaviour in large groups of domestic cats kept indoors. Applied Animal Behaviour Science 182, 23-29.

The domestic cat (Felis silvestris catus) originates from the solitary living African wildcat (Felis silvestris lybica). However, through domestication, the domestic cat has become more social towards conspecifics and group housing of cats is common...

Crast, J., Bloomsmith, M. A., Jonesteller, T. 2015. Effects of changing housing conditions on mangabey behavior (Cercocebus atys): Spatial density, housing quality, and novelty effects. American Journal of Primatology 77(9), 1001-1014.

The separate influences of spatial density and housing quality on the behavior of captive animals are difficult to measure because the two factors are often intrinsically linked. Here, we recorded affiliative and agonistic behavior in...

Moody, C. M., Makowska, I. J., Weary, D. M. 2015. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science 163, 183-87.

Laboratory mice are commonly killed via exposure to gradually increasing concentrations of isoflurane and carbon dioxide (CO2) gas. Once rendered insensible using isoflurane or CO2, a high concentration of CO2 is used to decrease time...

Young, M., Lawson, G. W., Duarte-Vogel, S. et al. 2014. Minimizing symptoms and stress in seizure-prone mice by using acupressure during routine handling. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 555 (Abstract #P29).

Many laboratory mice used in research experience spontaneous seizures during cage changing and routine handling. The triggers are usually the abrupt sound and sudden motion of the cage. These seizures can range from mild to...

Lambeth, S. P., Schapiro, S. J., Bernacky, B. J. et al. 2013. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates. Animal Welfare 22(4) 429-435.

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in...

Gruen, M. E., Thomson, A. E., Clary, G. P. et al. 2013. Conditionining laboratory cats to handling and transport. Lab Animal 42(10), 385-389.

As research subjects, cats have contributed substantially to our understanding of biological systems, from the development of mammalian visual pathways to the pathophysiology of feline immunodeficiency virus as a model for human immunodeficiency virus. Few...

Cruden, J., Bester, J., Baines, N. et al. 2013. Will a more consistent handling method lead to a calmer rabbit? Animal Technology and Welfare 11, 127-130.

The authors describe various methods of handling and restraining rabbits, and propose that while many methods are appropriate, rabbits respond better if only one method is used consistently.

Whittaker, A. L., Howarth, G. S., Hickman, D. L. 2012. Effects of space allocation and housing density on measures of wellbeing in laboratory mice: A review. Laboratory Animals 46(1), 3-13.

In the majority of countries where there are legislative requirements pertaining to the use of animals in research, figures are quoted for minimum cage sizes or space allocation to be provided per animal. These figures...