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...

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...

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...

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...

Beeby, N., Baden, A. L., Higham, J. P. 2023. Urinary C-peptide and total triiodothyronine as energetic biomarkers for studies of lemurs. American Journal of Primatology 85(12), e23563.

Measuring energy balance and energy metabolism can provide crucial information for understanding the ecological and behavioral drivers of an animal’s energetic and physiological condition. Both urinary C-peptide (uCP) of insulin and urinary total triiodothyronine (uTT3)...

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...

Webb, J. K., Keller, K. A., Chinnadurai, S. K. et al. 2023. Use of alfaxalone in bearded dragons (Pogona vitticeps): Optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography. Journal of the American Veterinary Medical Association 261(1), 126–131.

OBJECTIVE Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has...

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...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

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...

Takeshita, R. S. C. 2022. Validation of an enzyme immunoassay for measurement of fecal dehydroepiandrosterone sulfate in gibbons and siamangs. Zoo Biology 41(6), 544–553.

Monitoring wildlife stress levels is essential to ensure their quality of life in captivity or in the wild. One promising method to assess the stress response is the comeasurement of glucocorticoids (GC) and dehydroepiandrosterone sulfate...

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...

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...

Yolles, J. N., Lee-Stubbs, R. B. 2021. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy, anesthetized African green monkeys (Chlorocebus aethiops). JAALAS 60(2), 229-237.

Quantitative blood pressure measurement is a critical parameter for assessing cardiovascular health, monitoring physiologic status under anesthesia, and making clinical decisions. The placement of an arterial catheter is the most accurate way to measure blood...

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...

Byrnes, E. E., Lear, K. O., Morgan, D. L. et al. 2020. Respirometer in a box: Development and use of a portable field respirometer for estimating oxygen consumption of large‐bodied fishes. Journal of Fish Biology 96(4), 1045-1050.

Respirometry has become the standard method for measuring the metabolic rate of fishes. Traditionally, respirometry has required the fish to be kept in captivity and tested under controlled conditions; however, many species do not readily...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

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...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

Lawrence, M. J., Raby, G. D., Teffer, A. K. et al. 2020. Best practices for non-lethal blood sampling of fish via the caudal vasculature. Journal of Fish Biology 97(1), 4–15.

Blood sampling through the caudal vasculature is a widely used technique in fish biology for investigating organismal health and physiology. In live fishes, it can provide a quick, easy and relatively non‐invasive method for obtaining...

Rasys, A. M., Divers, S. J., Lauderdale, J. D. et al. 2020. A systematic study of injectable anesthetic agents in the brown anole lizard (Anolis sagrei). Laboratory Animals 54(3), 281–292.

Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...