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...

Kaiser, S., Korte, A., Wistuba, J. et al. 2023. Effects of castration and sterilization on baseline and response levels of cortisol—A case study in male guinea pigs. Frontiers in Veterinary Science 9, 1093157.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex...

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...

Ruvira, S., Rodríguez-Rodríguez, P., Cañas, S. et al. 2023. Evaluation of parameters which influence voluntary ingestion of supplements in rats. Animals 13(11), 1827.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based...

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...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

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...

Menard, J., Bagheri, S., Menon, S. et al. 2023. Noninvasive sampling of the small intestinal chyme for microbiome, metabolome and antimicrobial resistance genes in dogs, a proof of concept. Animal Microbiome 5(1), 64.

Background The gastrointestinal microbiome and metabolome vary greatly throughout the different segments of the gastrointestinal tract, however current knowledge of gastrointestinal microbiome and metabolome in health and disease is limited to fecal samples due to...

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...

Krall, C., Hopper, L. M., Hutchinson, E. K. 2023. Mice just want to have fun: Playpens facilitate faster training in non-invasive techniques for improved refinement and well-being. Laboratory Animal Science Professional 11(4) (July/August), 22-24.

Practical mechanisms that can be implemented by animal facilities to enhance refinement include the use of non-aversive handling, non-invasive alternative procedures, and additional environmental enrichment. Thus, we sought to collate these techniques by developing a...

Rexroat, E. K., Haughton, C. L., Fox, K. 2023. Using a cost-effective, efficient method to train young dogs to cooperate for multiple blood collection procedures in a pharmacokinetics study. Laboratory Animal Science Professional 11(6) (November/December), 34-36.

Behavioral testing slings, such as the Pavlov sling, offer an effective form of restraint for beagles while minimizing stress. Although these slings provide effective restraint, their high cost makes them less likely to be considered...

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...

Miguelena Chamorro, B., Swaminathan, G., Mundt, E. et al. 2023. Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance. Lab Animal 52(9), 195–197.

Oral vaccines are gaining attention for their ease of administration and ability to activate mucosal immune responses. However, preclinical studies using this route often require the use of gavage, which has limitations. In this comment...

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...

Riddell, D. L., Hyndman, T. H., Bowden, R. S. et al. 2023. Use of a low-calorie flavored gel to facilitate oral self-administration of analgesics in mice. JAALAS 62(2), 163–169.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to...

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...

Martins, T., Matos, A. F., Soares, J. et al. 2022. Comparison of gelatin flavors for oral dosing of C57BL/6J and FVB/N mice. JAALAS 61(1), 89-95.

Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture...

Bartlett, J., Davies, J., Purawijaya, D. et al. 2022. Refinement of handling and dosing methods for rats and mice. Animal Technology and Welfare 21(2), 120-124.

Modified Handling for Mice: Handling mice by gripping the base of the tail has been shown to negatively impact animal welfare by increasing anxiety and aversion to handling. We aimed to refi ne the dosing...

Donaldson-Wing, M. 2022. Medicated jelly as a replacement for injectables and the use of Maropitant to manage itchy skin in mice. Animal Technology and Welfare 21(2), 134-136.

It is desirable to administer drugs by the least invasive route to (1) optimise welfare, (2) reduce the risk of injury to animal handlers and (3) minimise the impact of restraint and transient pain on...

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...