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. 
Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

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...

Jorge, S., Félix, L., Costas, B. et al. 2023. Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status. Animals 13(6), 1120.

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is exposed daily may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for...

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...

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...

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...

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...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Boardman, R. M., Pinder, A. C., Piper,A. T. et al. 2022. Non-lethal sampling for the stable isotope analysis of the critically endangered European eel Anguilla anguilla: How fin and mucus compare to dorsal muscle. Journal of Fish Biology 100(3), 847-851.

Ecological studies on the critically endangered European eel Anguilla anguilla often incorporate stable isotope analysis that typically uses dorsal muscle sampled from euthanised eels. To minimise the lethal sampling of imperilled populations, fin tissue and/or...

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...

Chesler, K. C., Motz, C. T., Bales, K. L. et al. 2022. Voluntary oral dosing for precise experimental compound delivery in adult rats. Laboratory Animals 56(2), 147-156.

Preclinical drug studies routinely administer experimental compounds to animal models with the goal of minimizing potential adverse events from the procedure. In this study, we assessed the ability to train adult male Long Evans rats...

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...

Santymire, R. M., Young, M., Lenihan, E. et al. 2022. Preliminary investigation into developing the use of swabs for skin cortisol analysis for the ocean sunfish (Mola mola). Animals 12(20), 2868.

The ocean sunfish (mola; Mola mola) is the heaviest bony fish in the world. This slow-moving fish often is injured by fishing boats that use drift gillnets attributing to its listing as Vulnerable by the...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

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...

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...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Stevens, C., Hawkins, P., Smulders, T. V. et al. 2021. Report of the 2020 RSPCA/UFAW rodent and rabbit welfare meeting. Animal Technology and Welfare 20(1), 21-33.

The RSPCA/UFAW rodent and rabbit welfare group has held a one-day meeting every autumn for the last 27 years, so that its members can discuss current welfare research, exchange views on welfare issues and share...

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...

Satokar, V., Vickers, M., Bridge-Comer, P. et al. 2021. Emulsified gels: A refined vehicle for accurate and rapid oral administration of lipid based preparations to rats. Animal Technology and Welfare 20(2), 95-103.

Oro-gastric gavage is used to accurately administer nutritional substances or drugs to animals. However, it induces stress and has a substantial risk of mishap. Incorporation into edible gels is difficult for lipid-based preparations. We report...