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. 
Kaleel, K. L., Secoura, P. L., Muñoz-Pérez, J. P. et al. 2024. Endoscopy and rectal enema for fecal collection in wild sea turtles (Chelonia mydas, Eretmochelys imbricata) in a field setting. Zoo Biology 43(1), 55–60.

Forty-seven free-ranging sea turtles (46- Chelonia mydas, 1- Eretmochelys imbricata) were examined via novel use of an endoscopy combined with a rectal enema to obtain large fecal sample volumes. The cloaca was insufflated using an...

Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

Danforth, M. D., Clyde, V. L., Jourdan, B. et al. 2023. Blood pressure monitoring in zoologically managed bonobos (Pan paniscus). American Journal of Primatology 85(3), e23474.

In response to the growing evidence that hypertension may play a significant role in the development of cardiovascular disease (CVD) in bonobos, the Great Ape Heart Project established a finger blood pressure (BP) monitoring protocol...

Higham, J. P., Cooper, E. B., Whalen, C. et al. 2023. Urinary cytokine measurements do not reflect surgery-induced inflammation in rhesus macaques. American Journal of Primatology 85(8), e23506.

Measurement of the health and disease status of free-ranging primates is often limited by a lack of available biomarkers of immune activation and inflammation that can be applied noninvasively via the measurement of urine or...

Escribano, D., Contreras-Jodar, A., López-Arjona, M. et al. 2023. Changes in cortisol and cortisone in hair of pigs reared under heat stress conditions. Frontiers in Veterinary Science 10.

Heat stress accounts for millions of dollars in losses for swine producers worldwide. The aim of the present study was to determine and evaluate cortisol and cortisone in hair as indicators of thermal stress in...

Kastelic, M., Gregurić Gračner, G., Tomažič, I. et al. 2023. Comparison of cortisol concentrations in different matrices in Alpine ibex (Capra ibex) at the zoo. Animals 13(15), 2491.

The usefulness of blood collection using venipuncture versus kissing bugs or medicinal leeches and the collection of saliva, faeces, hair, urine, and tears for measuring “immunoreactive” C (iC) concentration in Alpine ibexes was verified using...

Ortín-Bustillo, A., Botía, M., López-Arjona, M. et al. 2023. Saliva sampling material matters: Effects on the results of saliva analysis in pigs. Animals 13(24), 3757.

The use of saliva as a biological sample from pigs is of high practical interest because blood collection from pigs is difficult and stressful. In this study, the influence of two different materials, a cotton...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

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...

Broche, N., Mouri, K., Suzumura, T. et al. 2023. Measuring short-term changes in stress-associated salivary analytes in free-ranging Japanese macaques (Macaca fuscata). Primates 64(4), 439–449.

Monitoring short-term changes of endocrine responses in non-human primates living in wild populations is a challenge. Saliva contains enzymes, steroids, and various analytes that can be broadly useful for helping us understand physiological responses to...

Zeltner, A., Cristofferson, C. 2022. Taking blood from a Göttingen minipig while placed in a sling. Animal Technology and Welfare 21(1), 58-61.

Traditionally Göttingen minipigs are restrained in dorsal recumbency to have access to the blood vessels in the neck. Minipigs, like any other animal do not particularly like to be restrained and being turned on their...

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...

Schilling, A.-K., Mazzamuto, M. V., Romeo, C. 2022. A review of non-invasive sampling in wildlife disease and health research: What’s new? Animals 12(13), 1719.

In the last decades, wildlife diseases and the health status of animal populations have gained increasing attention from the scientific community as part of a One Health framework. Furthermore, the need for non-invasive sampling methods...

Edes, A. N., Zimmerman, D., Jourdan, B. et al. 2022. Value ranges and clinical comparisons of serum DHEA-S, IL-6, and TNF-α in western lowland gorillas. Animals 12(19), 2705.

Physiological data can provide valuable information about the health and welfare of animals. Unfortunately, few validated assays and a lack of information on species-typical levels of circulating biomarkers for wildlife make the measurement, interpretation, and...

O’Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

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...

Navarro-Castilla, A., Garrido, M., Hawlena, H. et al. 2021. Non-invasive monitoring of adrenocortical activity in three sympatric desert gerbil species. Animals 11(1), 75.

The study of the endocrine status can be useful to understand wildlife responses to the changing environment. Here, we validated an enzyme immunoassay (EIA) to non-invasively monitor adrenocortical activity by measuring fecal corticosterone metabolites (FCM)...

Wang, M., Youssef, Al., Larsen, M. et al. 2021. Contactless video-based heart rate monitoring of a resting and an anesthetized pig. Animals 11(2), 442.

Heart rate (HR) is a vital bio-signal that is relatively easy to monitor with contact sensors and is related to a living organism’s state of health, stress and well-being. The objective of this study was...

Wiechers, D.-H., Brunner, S., Herbrandt, S. et al. 2021. Analysis of hair cortisol as an indicator of chronic stress in pigs in two different farrowing systems. Frontiers in Veterinary Science 8, 605078.

Confinement to farrowing crates is known to prevent sows from performing natural behavior, impairing animal welfare and possibly causing chronic stress. Hair cortisol analyses are increasingly used to detect chronic stress in animals. In the...

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...

Schmid, S. M., Büscher, W., Steinhoff-Wagner, J. 2021. Suitability of different thermometers for measuring body core and skin temperatures in suckling piglets. Animals 11(4), 1004.

Monitoring the temperature of piglets after birth is critical to ensure their well-being. Rectal temperature measurement is time-consuming, requires fixation of the animal and is stressful for piglets. This study aims to evaluate the effectiveness...

Manell, E., Hedenqvist, P., Jensen-Waern, M. 2021. Training pigs for oral glucose tolerance test—Six years’ experience of a refined model. Animals 11(6), 1677.

Animal models of human diseases are important in biomedical research. When using animals for scientific purposes, the 3Rs (replace, reduce, refine) should be considered. Refinement of animal models is essential to ensure best use of...

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...

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...