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. 
Mertens, S., Vogt, M. A., Gass, P. et al. 2019. Effect of three different forms of handling on the variation of aggression-associated parameters in individually and group-housed male C57BL/6NCrl mice. PLOS ONE 14(4), e0215367.

Mice are social animals hence group-housing of mice is preferred over individual housing. However, aggression in group-housed male mice under laboratory housing conditions is a well-known problem leading to serious health issues, including injury or...

Mechelinck, M., Kupp, C., Krüger, J. C. et al. 2019. Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study. PLOS ONE 14(12), e0226430.

A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and...

Gouveia, K., Hurst, J. L. 2019. Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice. Scientific Reports 9, 20305.

Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling...

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...

Ehrlich, O., Karamalakis, A., Krylov, A. J. et al. 2019. Clove oil and AQUI-S efficacy for zebrafish embryo, larva, and adult anesthesia. Zebrafish 16(5), 451-459.

Since the use of the zebrafish Danio rerio genetic model organism within the scientific research community continues to grow rapidly, continued procedural refinement to support high-quality, reproducible research and improve animal welfare remains an important...

Balko, J. A., Lindemann, D. M., Allender, M. C. et al. 2019. Evaluation of the anesthetic and cardiorespiratory effects of intramuscular alfaxalone administration and isoflurane in budgerigars (Melopsittacus undulatus) and comparison with manual restraint. Journal of the American Veterinary Medical Association 254(12), 1427-1435.

OBJECTIVE To evaluate the anesthetic and cardiorespiratory effects of IM alfaxalone and isoflurane administration in budgerigars (Melopsittacus undulatus) and compare use of these agents with use of manual restraint. ANIMALS 42 healthy budgerigars. PROCEDURES For...

Cox, R. J., Nol, P., Ellis, C. K. et al. 2019. Research with agricultural animals and wildlife. ILAR Journal 60(1), 66-73.

In fiscal year 2016, agricultural animals such as swine, sheep, goats, and cattle represented 10% of the 820 812 animals used in USDA-regulated research. In addition to traditional agricultural animals, research studies using captive wildlife...

Stevens, C. 2019. Refining handling for small laboratory fishes. Animal Technology and Welfare 18(3), 191-193.

Fishes in captivity, such as those used in laboratory research, may experience handling on a regular basis. In the laboratory, handling is usually done with dip-nets, and involves pursuit, confinement and capture and removal of...

Dunford, K., Hakkesteeg, J., Wilson, C. 2019. Stiff as a board: Measuring rigor mortis in zebrafish. Animal Technology and Welfare 18(3), 203-205.

Schedule one killing (S1K) methods require a two-step process: a humane method of death, typically for Zebrafish an anaesthetic overdose and confirmation of death, such as confirmation of rigor mortis. There is widespread variation of...

Ritchie, A., Collier, P., Clare, P. et al. 2019. Food for thought: The development of drug loaded diets improve both science and welfare. Animal Technology and Welfare 18(3), 222-224.

In our facility, we use several hormone dependent tumour models with supplementation delivered via slow release subcutaneously implanted pellets, implanted via trochar. For example, breast tumours which rely on 17-β-Estradiol. Administration of E2 supplementation can...

Thurman, C. E., Rasmussen, S., Prestia, K. A. 2019. Effect of 3 euthanasia methods on serum yield and serum cortisol concentration in zebrafish (Danio rerio). JAALAS 58(6), 823–828.

Zebrafish are an important model in neuroscience and developmental biology and are also an emerging model in hematology and immunology. Little information is available for zebrafish regarding the physiologic impact of different euthanasia methods and...

Doerning, C. M., Thurston, S. E., Villano, J. S. et al. 2019. Assessment of mouse handling techniques during cage changing. JAALAS 58(6), 767–773.

Mouse handling during cage changing and health evaluation has traditionally been performed by using forceps. This method was adopted as a biosecurity measure but can adversely affect employee ergonomics and rodent behavior. In this study...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

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...

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...

ter Horst, E. N., Krijnen, P. A. J., Flecknell, P. et al. 2018. Sufentanil–medetomidine anaesthesia compared with fentanyl/fluanisone–midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion. Laboratory Animals 52(3), 271-279.

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated...

Schuster, C. J., Pang, D. S. J. 2018. Forced-air pre-warming prevents peri-anaesthetic hypothermia and shortens recovery in adult rats. Laboratory Animals 52(2), 142-151.

General anaesthesia disrupts thermoregulation in mammals, which can cause hypothermia. Decreases in core body temperature of 1℃ cause significant postoperative complications in humans, and peri-anaesthetic hypothermia in mice increases data variability, which can potentially increase...

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...

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...

Wallace, C. K., Bright, L. A., Marx, J. O. et al. 2018. Effectiveness of rapid cooling as a method of euthanasia for young zebrafish (Danio rerio). JAALAS 57(1), 58-63.

Despite increased use of zebrafish (Danio rerio) in biomedical research, consistent information regarding appropriate euthanasia methods, particularly for embryos, is sparse. Current literature indicates that rapid cooling is an effective method of euthanasia for adult...

Clarkson, J. M., Dwyer, D. M., Flecknell, P. A. et al. 2019. Handling method alters the hedonic value of reward in laboratory mice. Scientific Reports 8, 2448.

Mice are the most widely used model species for drug discovery and scientific research. Consequently, it is important to refine laboratory procedures and practices to ensure high standards of welfare and scientific data quality. Recent...

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...

Swan, A. 2018. Refining mouse handling - do we or don't we? An animal technologist's perspective. Animal Technology and Welfare 17(2), 130-131.

Recent research in the industry identified that picking up mice in a tunnel or cupping them in the hand significantly reduces their stress levels. As Animal Tecgnologists, we could see advantages and disadvantages with this...

Hocking, A. J., Elliot, D., Hua, J. et al. 2018. Administering fixed oral doses of curcumin to rats through voluntary consumption. JAALAS 57(5), 508–512.

Curcumin, a polyphenol derived from turmeric, has a wide variety of therapeutic benefits including antiinflammatory, antioxidative, and chemopreventative effects. Oral gavage is widely performed to administer curcumin in laboratory rodents in several experimental models. Although...

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...