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. 
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...

Theil, J. H., Ahloy-Dallaire, J., Weber, E. M. et al. 2020. The epidemiology of fighting in group-housed laboratory mice. Scientific Reports 10(1), 16649.

Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most common potentially preventable morbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression...

Silber, S., Joshi, S., Pillay, N. 2019. Behavioural syndromes in stereotypic striped mice. Applied Animal Behaviour Science 212, 74-81.

Stereotypical behaviours (SBs) are abnormal, repetitive behaviours often observed in captivity. SBs are linked to impoverished captive conditions, and stereotypic individuals show a particular set of behaviours (e.g. bolder personality, greater activity) indicating proactive coping...

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...

Kroeker, R., Chichester, L., Lee, G. H. et al. 2019. Effects of pregnancy, outdoor access, and antifungal medication on hair loss in breeding-age female pigtailed macaques (Macaca nemestrina). Comparative Medicine 69(3), 221–227.

Over 18 mo, adult female pigtailed macaques (Macaca nemestrina) housed at a breeding facility in Arizona were monitored every 6 mo for alopecia. The study period coincided with the movement of a majority of animals...

Dutton III, J. W., Artwohl, J. E., Huang, X. et al. 2019. Assessment of pain associated with the injection of sodium pentobarbital in laboratory mice (Mus musculus). JAALAS 58(3), 373-379.

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined...

Moffitt, A. D., Brignolo, L. L., Ardeshir, A. et al. 2019. The role of emotional contagion in the distress exhibited by grouped mice exposed to CO2. JAALAS 58(4), 430-437.

The 2013 AVMA Guidelines for the Euthanasia of Animals recommends a chamber volume displacement rate of 10% to 30% per minute (v/min) when euthanizing small laboratory rodents with CO2. Group euthanasia of mice is a...

Poirier, C., Oliver, C. J., Castellano Bueno, J. et al. 2019. Pacing behaviour in laboratory macaques is an unreliable indicator of acute stress. Scientific Reports 9, 7476.

Pacing behaviour, the most frequent stereotypic behaviour displayed by laboratory rhesus macaques (Macaca mulatta) is often used as an indicator of stress. In this study, we investigated how reliable this welfare indicator is at detecting...

McMillan, F. D. (ed). 2019. Mental Health and Well-being in Animals (2nd ed). CABI, Wallingford, UK.

This second edition is fully revised, expanded, and comprehensively updated with the most current knowledge about the full array of mental health issues seen in animals. Written by key opinion leaders, internationally-recognized experts and specialists...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Lutz, C. K. 2018. A cross-species comparison of abnormal behavior in three species of singly-housed old world monkeys. Applied Animal Behaviour Science 199, 52-58.

Abnormal behavior occurs in a number of captive nonhuman primate species and is often used as an indicator of welfare. However, reported levels of abnormal behavior often vary across species, making general welfare judgments difficult...

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...

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...

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...

Heagerty, A., Wales, R. A., Prongay, K. et al. 2017. Social hair pulling in captive rhesus macaques (Macaca mulatta). American Journal of Primatology 79(12), e22720.

Alopecia is common among captive populations of nonhuman primates. There are many potential causes of alopecia, including physiological conditions such as hormonal imbalance and infection, features of the captive environment such as housing type, ground...

Novak, M. A., Menard, M. T., El-Mallah, S. N. et al. 2017. Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta). American Journal of Primatology 79(1), e22547.

Hair loss is common in macaque colonies. Very little is known about the relationship between psychological stress and hair loss. We initially examined alopecia and hair cortisol concentrations in 198 (89 male) rhesus macaques from...

Kroeker, R., Lee, G. H., Bellanca, R. U. et al. 2017. Prior facility affects alopecia in adulthood for rhesus macaques. American Journal of Primatology 79(1), e22551.

Alopecia has proven to be a persistent problem for captive macaques; many cases continue to elude explanations and effective treatments. Although almost all captive populations exhibit alopecia rates higher than those seen in the wild...

Dettmer, A. M., Rosenberg, K., Menard, M. T. et al. 2017. Differential relationships between chronic hormone profiles in pregnancy and maternal investment in rhesus monkey mothers with hair loss in the neonatal period. American Journal of Primatology 79(1), e22489.

Hair loss is commonly used as an indicator of well being in primate facilities, yet it has been shown to also occur in otherwise healthy pregnant and postpartum females. There is significant variability in the...

Martin, A. L. 2017. Theprimatologist as a behavioral engineer. American Journal of Primatology 79, e22500.

The field of primate behavior management has had only limited success in preventing and treating abnormal behaviors, such as stereotypy and self‐injury, in captive non‐human primates (NHP). In contrast, applied behavior analysts have had great...