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. 
Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

Esparza, K. 2023, August. Moving away from soiled bedding sentinels—The (R)evolution in rodent health screening. Animal Technology and Welfare 22(2), 158–160.

Traditional health monitoring methods consisted of Soiled Bedding Sentinels (SBS (i.e. animals exposed to dirty bedding from colony animals)), which require the euthanasia of SBS. Numerous studies have demonstrated that SBS may not accurately represent...

Marin, N., Moragon, A., Gil, D. et al. 2023. Acclimation and blood sampling: Effects on stress markers in C57Bl/6J mice. Animals 13(18), 2816.

Blood sampling in rodents is common practice in scientific studies. Some of the refined methods widely used are the puncture of the saphenous vein or tail vein, or even tail docking. The handling needs of...

Brown, A. 2023. Aced it! Performing large volume survival bleeds in rabbits. Laboratory Animal Science Professional 11(3) (May/June), 44-46.

New Zealand White rabbits are commonly used for polyclonal antibody production, which can require collecting no more than 10% of total body weight every two weeks (approximately 20 ml of blood for a 4 kg...

Anderson, B. J., Curtis, A. M., Jen, A. et al. 2023. Plasma metabolomics supports non-fasted sampling for metabolic profiling across a spectrum of glucose tolerance in the Nile rat model for type 2 diabetes. Lab Animal 52(11), 269–277.

Type 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic...

Bertani, S., Donadi, A., Franchi, J. et al. 2023. Blood microsampling in cynomolgus monkey and evaluation of plasma PK parameters in comparison to conventional sampling. Journal of Pharmacological and Toxicological Methods 123, 107298.

Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive...

Buhr, P., Kolstrup, S., Nikolajsen, L.-L. et al. 2023. The anaesthetic effects of ketamine/xylazine/midazolam in C57Bl/6JRj mice. Scandinavian Journal of Laboratory Animal Science 49, 21–27.

We wished to improve the efficacy and safety of ketamine/xylazine anaesthesia in C57Bl/6JRj mice and achieve a surgical anaesthesia lasting 20-30 minutes, aiming at fewer anaesthesia related deaths and using the subcutaneous injection route to...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

George, A. J., O’Malley, C. I., Bulock, R. E. et al. 2023. Implementation of an alternative training method for cardiac blood collection in mice. JAALAS 62(6), 487–493.

Training personnel to work with animals presents a variety of challenges, both logistically and with regard to animal welfare. These issues make training an ideal opportunity to evaluate practices and to implement the 3R principles...

George, A. J., Harmsen, B. J., Ford, J. A. et al. 2023. Evaluation of submental blood collection in mice (Mus musculus). JAALAS 62(1), 92–98.

The submental route is an option for nonterminal and serial blood collection in mice. This study compared the submental route to the maxillary route (also referred to as the submandibular route). The study used male...

Gilberto, D., Michener, M., Smith, B. et al. 2022. Chronic collection of cerebrospinal fluid from rhesus macaques (Macaca mulatta) with cisterna magna ports: Update on refinements. Comparative Medicine 72(1), 45-49.

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus...

Ahrens Kress, A. P., Zhang, Y., Kaiser-Vry, A. R. et al. 2022. A Comparison of blood collection techniques in mice and their effects on welfare. JAALAS 61(3), 287-295.

Multiple methods are used to collect blood from mice; these methods have different effects on animal welfare. This study compared blood collection from facial, chin, and saphenous locations with regard to various parameters, including the...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Giral, M., Armengol, C., Gavaldà, A. 2022. Physiologic effects of housing rats in metabolic cages. Comparative Medicine 72(5), 298–305.

Currently, metabolic cages (MC) are the only way to achieve serial sampling of urine and feces in rodents. However, the use of this caging creates a dramatic change from an animal’s usual microenvironment. Here we...

Álvarez, E. R., Solé, L. V., Mateo, A. G. de C. 2022. Comparison of subcutaneous sedation with alfaxalone or alfaxalone-midazolam in pet guinea pigs (Cavia porcellus) of three different age groups. Journal of the American Veterinary Medical Association 260(9), 1024–1030.

OBJECTIVE To compare the cardiorespiratory effects, quality and duration of sedation of 2 subcutaneous sedation protocols for noninvasive procedures in guinea pigs (GPs). ANIMALS 24 pet GPs (15 females, 9 males) of 3 different age...

Huss, M. K., Pacharinsak, C. 2022. A review of long-acting parenteral analgesics for mice and rats. JAALAS 61(6), 595–602.

Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data...

Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...

Stow, R., Kendrick, J., Ibbotson, N. et al. 2021. A new group housing approach for non-human primate metabolism studies. Journal of Pharmacological and Toxicological Methods 107, 106947.

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals...

Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...