Replacement, reduction, refinement: 3 days for 3Rs

Caloni, Francesca

doi:10.14573/altex.2206271

Cited by 23 publications

(29 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additional reference groups, and consequently more animals, are needed if appropriate historical control data are not available at the testing facility. This practice is consistent with the principles of humane animal experimentation [45,49,64], that were first defined as the "3 R's" of reduce, refine, and replace, in 1959 [99]. Historical control data provide context in the determination of whether any differences observed between treatment groups are the result of natural biological variability or related to treatment.…”

Section: Discussionmentioning

confidence: 64%

“…All of the recommended maximum incorporation rates (see Table 1) are based on both published and unpublished data and reflect experiences from conducting and analyzing 90-day rat feeding studies to meet regulatory requirements for GM products intended for use in food or feed. Although in the absence of testable hypotheses, arguments against conducting these studies have been put forth [9,60,108,113,137]; if the studies are to be conducted, then resources including time and animal lives must be used wisely [45,49,64].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Recommendations for Maximum Incorporation Rates of Whole Food in 90-Day Rat Feeding Studies

Goodwin

Glenn²,

Petrick

et al. 2021

View full text Add to dashboard Cite

More than 25 years of 90-day rat feeding studies with GM crops have consistently shown that these studies provide no additional value to safety assessments in the absence of a testable hypothesis. However, some regulatory authorities continue to require these studies while also specifying that the test material should be relevant to the product to be consumed and tested at the maximum incorporation rate not causing nutritional imbalance. In the absence of known or suspected adverse effects, dose range-finding studies are not feasible, yet scientifically justified incorporation rates are needed to balance the nutritional requirements of the animals and to achieve the goal of observing adverse effects, should they occur. When 90-day rat feeding studies are required for GM crop safety assessments, the following maximum incorporation rates (w/w), are recommended: 50 percent maize, 30 percent soybean, 60 percent rice, 15 percent canola, and 10 percent cottonseed. These recommendations are based on empirical data regarding maximum exposure to test material and avoidance of nutritional imbalances and/or exposure to anti-nutrients or toxins naturally present in the whole food. Each recommended maximum incorporation rate provides test material consumption at levels substantially higher than the highest human worldwide chronic consumption and is fully sufficient to address regulatory requirements. https://doi.org/10.21423/jrs-v09i2goodwin

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Recommendations for Maximum Incorporation Rates of Whole Food in 90-Day Rat Feeding Studies

Goodwin

Glenn²,

Petrick

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, the biomedical research direction follows the 3Rs principle (replacement, reduction, and refinement), to minimize the use of animal models when valid alternatives are available. 18…”

Section: D Versus 3d Culture: In What They Differmentioning

confidence: 99%

Emerging Strategies in 3D Culture Models for Hematological Cancers

Barozzi

Scielzo

2023

HemaSphere

View full text Add to dashboard Cite

In vitro cell cultures are fundamental and necessary tools in cancer research and personalized drug discovery. Currently, most cells are cultured using two-dimensional (2D) methods, and drug testing is mainly performed in animal models. However, new and improved methods that implement three-dimensional (3D) cell-culturing techniques provide compelling evidence that more advanced experiments can be performed, yielding valuable new insights. In 3D cell-culture experiments, the cell environment can be manipulated to mimic the complexity and dynamicity of the human tissue microenvironment, possibly leading to more accurate representations of cell-to-cell interactions, tumor biology, and predictions of drug response. The 3D cell cultures can also potentially provide alternative ways to study hematological cancers and are expected to eventually bridge the gap between 2D cell culture and animal models. The present review provides an overview of the complexity of the lymphoid microenvironment and a summary of the currently used 3D models that aim at recreating it for hematological cancer research. We here dissect the differences and challenges between, and potential advantages of, different culture methods and present our vision of the most promising future strategies in the hematological field.

show abstract

“…Russel and Burch described the “3Rs” of animal research in 1959, which are replacement, reduction and refinement [ 3 ]. Ex vivo porcine hepatic perfusion provides important data and for many studies is a successful alternative to live animal experiments.…”

Section: Introductionmentioning

confidence: 99%

“…To our knowledge, there are currently no reported studies describing ex vivo perfusion of an isolated hepatic segment [ 6 ]. The development of a novel ex vivo human liver segmental perfusion model would address the three principles of replacement, reduction and refinement and provide a versatile model for a wide range of pre-clinical studies [ 3 ]. We describe the development of a porcine ex vivo hepatic segmental perfusion model to demonstrate proof of concept and support further research into the ex vivo perfusion of human liver segments.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Ex Vivo Porcine Hepatic Segmental Perfusion Proof-of-Concept Model Towards More Ethical Translational Research

Kanani¹,

Isherwood²,

ElSamani³

et al. 2023

Cureus

View full text Add to dashboard Cite

IntroductionEx vivo machine perfusion describes the technique where organs are continuously perfused and oxygenated extracorporeally (at physiological conditions) to maintain the organs' viability. To our knowledge, there are currently no reported studies describing ex vivo perfusion of a single hepatic segment. Here, we describe the development of a porcine ex vivo hepatic segmental perfusion model to demonstrate proof of concept and support further research into the ex vivo perfusion of the human liver using discarded tissue. MethodsWhole livers were retrieved from abattoir-derived pigs and connected to a normothermic extracorporeal perfusion circuit. Constant segmental perfusion via the common or segmental hepatic artery and portal vein with heparinised autologous blood was established. The viability of the perfused organ was assessed by monitoring perfusion pressures, flow rates and histology samples. ResultsFollowing perfusion and optimisation of the model for three hepatic segments, the third perfusion demonstrated viable hepatocytes centrally after 4 h of segmental perfusion. ConclusionEx vivo hepatic segmental perfusion is technically challenging but its success in a porcine model and the principles learned should facilitate the development of an analogous human model using discarded tissue following formal liver resections. The model would use a healthy liver segment following a major formal resection such as a hemi-hepatectomy and ex vivo perfusion performed via a segmental hepatic artery and portal vein. If successful this model would represent a significant development and enable ethical translation research to assess the response of human livers to a variety of stressors, including toxicity and infection.

show abstract

Replacement, reduction, refinement: 3 days for 3Rs

Cited by 23 publications

References 5 publications

Recommendations for Maximum Incorporation Rates of Whole Food in 90-Day Rat Feeding Studies

Recommendations for Maximum Incorporation Rates of Whole Food in 90-Day Rat Feeding Studies

Emerging Strategies in 3D Culture Models for Hematological Cancers

Development of a Novel Ex Vivo Porcine Hepatic Segmental Perfusion Proof-of-Concept Model Towards More Ethical Translational Research

Contact Info

Product

Resources

About