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. 
Paterson, E. A., Turner, P. V. 2022. Challenges with assessing and treating pain in research primates: A focused survey and literature review. Animals 12(17), 2304.

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and...

Chan, G., Si, C., Nichols, M. R. et al. 2022. Assessment of the safety and efficacy of pre-emptive use of extended-release buprenorphine for mouse laparotomy. JAALAS 61(4), 381-387.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR...

Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...

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...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Kishida, T., Motokawa, Y., Yokoi, R. et al. 2022. Less invasive, simultaneous, and continuous measurements of locomotor activity and body temperature using the nano tag® small accelerometer device in cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 118, 107224.

Locomotor activity and body temperature evaluations of cynomolgus monkeys are useful to understand the effects of drugs on the central nervous system. Here, we describe a simple, inexpensive, and less invasive evaluation method using the...

Zeng, Y., Jin, H., Wang, J. et al. 2022. An optimized method for intratracheal instillation in mice. Journal of Pharmacological and Toxicological Methods 118, 107230.

Non-invasive intratracheal instillation is an important method for direct exposure of the respiratory tract which is commonly used in toxicology, environmental science, and other research fields. However, there is no standard operating process for non-invasive...

Kendall, L. V., Singh, B., Bailey, A. L. et al. 2021. Pharmacokinetics and efficacy of a long-lasting, highly concentrated buprenorphine solution in mice. JAALAS 60(1), 64-71.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate...

Robinson, L. M., Waran, N. K., Handel, I. et al. 2021. Happiness, welfare, and personality in rhesus macaques (Macaca mulatta). Applied Animal Behaviour Science 236, 105268.

When we treat an animal’s welfare as an individual experience, we should consider the possibility that it may be associated with individual differences in personality. We tested for such associations in 44 socially housed rhesus...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

Pomerantz, O., Capitanio, J. P. 2021. Temperament predicts the quality of social interactions in captive female rhesus macaques (Macaca mulatta). Animals 11(8), 2452.

Previous reports suggest that female macaques with greater similarity in emotionality and nervous temperament, as evaluated in a well-established BioBehavioral Assessment (BBA) at the California National Primate Research Center, were more likely to form successful...

Le Balle, R., Cote, J., Santos Fernandez, F. A. 2021. Evidence for animal personalities in two Brazilian tortoises (Chelonoidis denticulatus and Chelonoidis carbonarius) and insights for their conservation. Applied Animal Behaviour Science 241, 105400.

Animal personality, the consistent between-individual differences in e.g., risk-taking, exploration, antipredator or mating behaviours, has major impacts on the fitness of individuals in many species. Understanding how to quantify animal personality should help us predicting...

de A. P. Ramos, G., de Azevedo, C. S., Jardim, T. H. A. et al. 2021. Temperament in captivity, environmental enrichment, flight ability, and response to humans in an endangered parrot species. Journal of Applied Animal Welfare Science 24(4), 379-391.

Temperament assessment is useful in reintroduction programs. Reactivity to humans and flight ability are also important behavioral aspects for captive parrots candidates to reintroduction. The study aimed: a) to evaluate if behavioral responses to environmental...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Furumoto, K., Ogita, K., Kamisaka, T. et al. 2021. Effects of multimodal analgesic protocol, with buprenorphine and meloxicam, on mice well-being: A dose finding study. Animals 11(12), 3420.

The anesthetic or analgesic agent of choice, route and frequency of anesthetic or analgesic administration, and stressors induce distress during the perioperative period. We evaluated a multimodal analgesic protocol using buprenorphine and meloxicam on the...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...

Verjat, A., Devienne, P., Rödel, H. G. et al. 2021. More exploratory house mice judge an ambiguous situation more negatively. Animal Cognition 24(1), 53–64.

Exploration tendency, one of the most investigated animal personality traits, may be driven by either positive (when seeking interesting information) or negative (to reduce the uncertainty of the environment) affective/emotional profiles. To disentangle the valence...

Anderson, J., Kaplan-Stein, S., Adolph, S. et al. 2020. Assessment of non-contact infrared thermometer measurement sites in birds. Journal of Applied Animal Welfare Science 23(2), 131-139.

The standard method of obtaining body temperature in a bird can be a stressful event, making routine evaluations challenging. Twenty-eight privately owned birds in good health were enrolled in the study to compare digital and...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

Boers, K. L., Allender, M. C., Novak, L. J. et al. 2020. Assessment of hematologic and corticosterone response in free-living eastern box turtles (Terrapene carolina carolina) at capture and after handling. Zoo Biology 39(1), 13-22.

Hematology is a common tool for wildlife health assessments. Manual leukocyte counts are required in reptiles, however, disagreement between quantification methods has been observed in some chelonians. This study determined agreement between two methods of...

Nøgaard, S. A., Sand, F. W., Sørensen, D. B. et al. 2020. Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice. Animal Welfare 29(2), 143-149.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Foley, P. L., Kendall, L. V., Turner, P. V. 2019. Clinical management of pain in rodents. Comparative Medicine 69(6), 468–489.

The use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. Factors contributing to this gap...