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. 
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...

Kendrick, J., Stow, R., Ibbotson, N. et al. 2020. A novel welfare and scientific approach to conducting dog metabolism studies allowing dogs to be pair housed. Laboratory Animals 54(6), 588-598.

Metabolism cages are designed to conduct absorption, distribution, metabolism and excretion (ADME) studies, enabling an ‘excretion balance’ scientific objective to be met. Historically, the design of dog metabolism cages has involved single housing. This type...

Kulkarni, S., Hickman, D. 2020. Isoflurane and carbon dioxide elicit similar behavioral responses in rats. Animals 10(8), 1431.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to...

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...

Association of Primate Veterinarians. 2019. Association of Primate Veterinarians’ Position Statement: Cerebrospinal fluid aspiration for nonhuman primates in biomedical research. JAALAS 58(4), 428-429.

The Association of Primate Veterinarians (APV) recognizes that CSF collection may be required for both clinical and research purposes in nonhuman primates (NHP). Because there are inherent risks associated with the technique, the laboratory animal...

Lensen, C. M. M., Moons, C. P. H., Diederich, C. 2015. Saliva sampling in dogs: How to select the most appropriate procedure for your study. Journal of Veterinary Behavior 10(6), 504-512.

Saliva sampling is an easy, noninvasive method to assess short-term physiological changes, and as such is a valuable addition to behavioral studies in dogs. Different methods for collecting saliva samples in dogs have been reported...

Ishizuka, S., Kawamoto, Y., Toda, K. et al. 2019. Bonobos’ saliva remaining on the pith of terrestrial herbaceous vegetation can serve as non-invasive wild genetic resources. Primates 60(1), 7–13.

Evaluating the genetic diversity of natural populations of endangered species is important for conservation. Although the genetic analysis of wildlife usually requires collecting DNA non-invasively, the variety of non-invasive DNA sampling methods is limited for...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Harikrishnan, V. S., Hansen, A. K., Abelson, K. S. P. et al. 2018. A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare. Laboratory Animals 52(3), 253-264.

This study was conducted to investigate the effects of blood sampling on animal welfare in a total of 60 NTac:SD rats and 72 C57BL/6NTac mice of both sexes. Blood was sampled either by sublingual vein...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

Hoffman, J. F., Fan, A. X., Neuendorf, E. H. et al. 2018. Hydrophobic sand versus metabolic cages: A comparison of urine collection methods for rats (Rattus norvegicus). JAALAS 57(1), 51-57.

A common method for urine collection from rats requires the use of a metabolic cage, thus exposing animals to extended periods of isolation in an unfamiliar cage with a wire-mesh floor. A new method involving...

Phillips, K.A., Tukan, A. N., Rigodanzo, A. D. et al. 2018. Quantification of hair cortisol concentration in common marmosets (Callithrix jacchus) and tufted capuchins (Cebus apella). American Journal of Primatology 80(7), e22879.

Quantifying cortisol concentration in hair is a non‐invasive biomarker of long‐term hypothalamic‐pituitary‐adrenal (HPA) activation, and thus can provide important information on laboratory animal health. Marmosets (Callithrix jacchus) and capuchins (Cebus apella) are New World primates...

Hickman D. L. 2018. Interpreting neuroendocrine hormones, corticosterone, and blood glucose to assess the wellbeing of anesthetized rats during euthanasia. JAALAS 57(6), 725–728.

Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute...

Hickman D. L. 2018. Home cage compared with induction chamber for euthanasia of laboratory rats. JAALAS 57(6), 729–733.

This study compared behavioral and physiologic changes in Sprague–Dawley and Brown Norway rats that were euthanized by using a 30% volume displacement rate of CO2 in either their home cage or an induction chamber; rats...

Taylor, R. M., Miller, P. R., Ebrahimi, P. et al. 2018. Minimally-invasive, microneedle-array extraction of interstitial fluid for comprehensive biomedical applications: Transcriptomics, proteomics, metabolomics, exosome research, and biomarker identification. Laboratory Animals 52(5), 526–530.

Interstitial fluid (ISF) has recently garnered interest as a biological fluid that could be used as an alternate to blood for biomedical applications, diagnosis, and therapy. ISF extraction techniques are promising because they are less...

Byrd, R., Boyd, S., Buckmaster, C. 2018. Rat thunder jacket— A zen experience. Laboratory Animal Science Professional 6(3) (September), 55-57.

Germ-free rats are fairly uncommon, relative to germ-free mice, and restraining these animals safely and effectively for compound administration and blood collection can be challenging. There are many commercially available varieties of restraint devices, but...

Amen, E. M., Brecheisen, M., Sach-Peltason, L. et al. 2017. Refinement of a model of repeated cerebrospinal fluid collection in conscious rats. Laboratory Animals 51(1), 44-53.

The cannulation of the cisterna magna in rats for in vivo sampling of cerebrospinal fluid serves as a valuable model for studying the delivery of new drugs into the central nervous system or disease models...

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...

Scott, K. E., Bracchi, L. A., Lieberman, M. T. et al. 2017. Evaluation of best practices for the euthanasia of zebra finches (Taeniopygia guttata). JAALAS 56(6), 802-806.

Although zebra finches (Taeniopygia guttata) have been used in biomedical research for many years, no published reports are available about euthanizing these small birds. In this study, we compared 5 methods for zebra finch euthanasia...

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...

Rapp-Santos, K. J., Altamura, L. A., Norris, S. L. et al. 2017. Comparison of saliva collection methods for the determination of salivary cortisol levels in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and African green monkeys (Chlorocebus aethiops). JAALAS 56(2), 181-189.

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device...

Hawkins, P., McNeilly, A., Watson, J. et al. 2017. Report of the 2016 RSPCA/UFAW Rodent and Rabbit Welfare Group meeting. Animal Technology and Welfare 16(2), 77-86.

The RSPCA/UFAW Rodent (and now Rabbit) Welfare Group held a one-day meeting on 1 November 2016 at the University of Edinburgh and was attended by 70 delegates. Presentation topics included refinements in blood sampling rodents...