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. 
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...

Raya, J., Neves Girardi , C. E., Hipólide, D. C. 2019. Corticosterone assimilation by a voluntary oral administration in palatable food to rats. Journal of Applied Animal Welfare Science 22(1), 37-41.

Drug delivery in research on nonhuman animals in the laboratory is still challenging because it is usually invasive and stressful. Stress-free voluntary oral drug administration in water lacks precise control of dose and timing of...

Collymore, C., Kent, L., Ahn, S. K. et al. 2018. Humane endpoints for guinea pigs used for Mycobacterium tuberculosis vaccine research. Comparative Medicine 68(1), 41–47.

Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored...

Toth, L. A. 2018. Identifying and implementing endpoints for geriatric mice. Comparative Medicine 68(6), 439–451.

The types of changes in physical appearance and behavior that occur in elderly people similarly develop in elderly animals. Signs and symptoms that might cause concern in younger people or mice may be normal in...

Neff, E. P. 2018. Home sweet home cage. Lab Animal 47(10), 261–264.

This feature describes creative ways in which technology can be used to study animals within their home cages, eliminating the need to handle, restrain, and separate them from cage mates. One example includes voluntary brain...

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...

Benedict, D., Megrath, B. 2018. Upgrades to nonhuman primate tethered infusion system. Laboratory Animal Science Professional 6(3) (September), 62-64.

Continuous tethered infusions in any animal model pose a unique set of problems. These problems are amplified when nonhuman primates are the model. A high tolerance to the tether system by an animal model is...

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...

Rodrigues, M. V., de Castro, S. O., de Albuquerque, C. Z. 2017. The gingival vein as a minimally traumatic site for multiple blood sampling in guinea pigs and hamsters. PLOS ONE 12(5), e0177967.

Laboratory animals are still necessary in scientific investigation and vaccine testing, but while novel methodological approaches are not available for their replacement, the search for new, humane, easy, and painless methods is necessary to diminish...

Burden, N., Kendrick, J., Knight, L. et al. 2017. Maximizing the success of bile duct cannulation studies in rats: Recommendations for best practice. Laboratory Animals 51(5), 457-464.

Bile duct cannulation (BDC) studies are usually carried out in the rat to support the absorption, distribution, metabolism and excretion profiling of novel agrochemicals and pharmaceuticals. The different aspects of these studies (e.g. surgical preparation...

Jensen, V. F. H., Mølck, A.-M., Martensson, M. et al. 2017. Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: Potential for group housing. Laboratory Animals 51(3), 273-283.

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin...

Miranda, A., Pego, J. M., Correia-Pinto, J. 2017. Animal facility videoendoscopic intubation station: Tips and tricks from mice to rabbits. Laboratory Animals 51(2), 204-207.

Endotracheal intubation of laboratory animals is a common procedure shared by several research fields for different purposes, such as mechanical ventilation of anaesthetized animals, instillation of cytotoxic nanoparticles, infectious agents or tumour cells for induction...

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...

Tavera-Mendoza, L. E., Brown, M. 2017. A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland. Laboratory Animals 51(1), 85-88.

Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an...

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...

Gaskill, B. N., Stottler, A. M., Garner, J. P. et al. 2017. The effect of early life experience, environment, and genetic factors on spontaneous home-cage aggression-related wounding in male C57BL/6 mice. Lab Animal 46(4), 176-184.

Aggression is a major welfare issue in mice, particularly when mice unfamiliar to each other are first placed in cages, as happens on receipt from a vendor, and following cage cleaning. Injuries from aggression are...

Hubbard, J. S., Chen, P. H., Boyd, K. L. 2017. Effects of repeated intraperitoneal injection of pharmaceutical-grade and nonpharmaceutical-grade corn oil in female C57BL/6J mice. JAALAS 56(6), 779-785.

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all...

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...

Moore, E. S., Cleland, T. A., Williams, W. O. et al. 2017. Comparing phlebotomy by tail tip amputation, facial vein puncture, and tail vein incision in C57BL/6 mice by using physiologic and behavioral metrics of pain and distress. JAALAS 56(3), 307-317.

Tail tip amputation with minimal restraint is not widely used for mouse phlebotomy. In part, this infrequency may reflect policies influenced by tail tip amputation procedures for genotyping, which involve greater handling and tissue removal...

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...

Head, V., Eshar, D., Nau, M. R. 2017. Techniques for nonterminal blood sampling in black-tailed prairie dogs (Cynomys ludovicianus). JAALAS 56(2), 210-213.

Black-tailed prairie dogs (Cynomys ludovicianus) are used as an animal model for research on gallbladder stones and several infectious diseases. A comprehensive, instructive resource regarding the appropriate techniques for venipuncture and collection of nonterminal blood...

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...