Assessment of haematological and clinical pathology effects of blood microsampling in suckling and weaned juvenile rats

Powles-Glover, Nicola; Kirk, Sarah B.; Jardine, Lynne; Clubb, Stephanie; Stewart, Jane

doi:10.1016/j.yrtph.2014.05.006

Cited by 17 publications

(7 citation statements)

References 5 publications

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“…Generally speaking, expected procedure-related effects may include decreased RBC mass, and increased reticulocyte counts with associated increased splenic weights and splenic extramedullary hematopoiesis. 47,48,50 Other effects that have been reported include minor decreases in urea and increases in sodium. 50 Collecting TK blood from toxicity animals may induce a regenerative hematopoietic response that could mask subtle test article-related hematotoxicity, normally detected as a decrease in reticulocyte counts.…”

Section: Combining Tk and Cp Testing In The Same Cohortsmentioning

confidence: 97%

“…Several researchers have evaluated the impact of TK collections on CP variables in rats, and have reported minimal effects that were generally due to repeated handling (mild stress leukogram) or prior blood collection (lower RBC mass, increased reticulocyte counts) . Microsampling for TK prior to CP testing in adult and juvenile rats resulted in minor decreases in HGB concentration and minor increases in monocyte counts, as well as minimally lower body weight gains . Blood volumes of 200 μL collected from the saphenous vein in rats at 6 time points over 24 hours resulted in lower RBC mass.…”

Section: Opportunities For Reducing Animal Usementioning

confidence: 99%

“…Collection of blood volumes up to 1.2 mL (6 time points of 200 μL each) over 24 hours for up to one month in rats did not interfere with toxicity assessment in regulatory toxicity studies. Generally speaking, expected procedure‐related effects may include decreased RBC mass, and increased reticulocyte counts with associated increased splenic weights and splenic extramedullary hematopoiesis . Other effects that have been reported include minor decreases in urea and increases in sodium .…”

Section: Opportunities For Reducing Animal Usementioning

confidence: 99%

“…46 Microsampling for TK prior to CP testing in adult and juvenile rats resulted in minor decreases in HGB concentration and minor increases in monocyte counts, as well as minimally lower body weight gains. 47,48 Blood volumes of 200 lL collected from the saphenous vein in rats at 6 time points over 24 hours resulted in lower RBC mass. Furthermore, this blood volume could not be obtained consistently for all time points and sampling was frequently associated with hematomas at the blood sampling site.…”

Section: Combining Tk and Cp Testing In The Same Cohortsmentioning

confidence: 99%

See 3 more Smart Citations

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Poitout-Belissent

Aulbach

Tripathi

et al. 2016

Veterinary Clinical Pathol

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In preclinical safety assessment, blood volume requirements for various endpoints pose a major challenge. The goal of this working group was to review current practices for clinical pathology (CP) testing in preclinical toxicologic studies, and to discuss advantages and disadvantages of methods for reducing blood volume requirements. An industry-wide survey was conducted to gather information on CP instrumentation and blood collection practices for hematology, clinical biochemistry, and coagulation evaluation in laboratory animals involved in preclinical studies. Based on the survey results and collective experience of the authors, the working group proposes the following "points to consider" for CP testing: (1) For most commercial analyzers, 0.5 mL and 0.8 mL of whole blood are sufficient for hematology and biochemistry evaluation, respectively. (2) Small analyzers with low volume requirements and low throughput have limited utility in preclinical studies. (3) Sample pooling or dilution is inappropriate for many CP methods. (4) Appropriate collection sites should be determined based on blood volume requirements and technical expertise. (5) Microsampling does not provide sufficient volume given current analyzer and quality assurance requirements. (6) Study design considerations include: the use of older/larger animals (rodents), collection of CP samples before toxicokinetic samples, use of separate subsets of mice for hematology and clinical biochemistry testing, use of a priority list for clinical biochemistry, and when possible, eliminating coagulation testing.

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Section: Combining Tk and Cp Testing In The Same Cohortsmentioning

confidence: 97%

Section: Opportunities For Reducing Animal Usementioning

confidence: 99%

Section: Opportunities For Reducing Animal Usementioning

confidence: 99%

Section: Combining Tk and Cp Testing In The Same Cohortsmentioning

confidence: 99%

See 2 more Smart Citations

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Poitout-Belissent

Aulbach

Tripathi

et al. 2016

Veterinary Clinical Pathol

View full text Add to dashboard Cite

show abstract

“…Significant refinements can be realized through implementation of microsampling approaches, as the procedure can be completed in less time and with only minimal restraint, reducing stress for the animal. For rodents, the duration animals have to be placed into a warming chamber prior to blood collection can be reduced ( Powles-Glover et al 2014a , 2014b ). Additionally, the use of closed blood collection systems removes the potential for overfilling of tubes and can minimize the total blood loss as well as enabling researchers to more accurately assess the total volume of blood loss.…”

Section: Improvement Of Proceduresmentioning

confidence: 99%

Opportunities to Apply the 3Rs in Safety Assessment Programs

Sewell

Edwards

Prior

et al. 2016

ILAR J

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Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans.

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Impact of microsampling on toxicological evaluation in rodent safety studies

Takahashi,

Hattori,

Yokoyama

et al. 2023

J of Applied Toxicology

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Recently, animal welfare has been attracting worldwide attention, and implementation of 3Rs (replacement, reduction, and refinement) is prioritized in every way possible in the drug development. Microsampling, in which small amounts of blood are collected, is attracting attention in this context. ICH S3A Q&A focused on microsampling was published in November 2017 to help accelerate the application of microsampling for toxicokinetic assessment. The increased sensitivity of drug measurement apparatuses such as mass spectrometers has made it possible to measure drug concentrations with small amounts of blood samples. In this review, we summarized the reports on toxicological influence of microsampling in rodents (rats and mice) with or without drug administration or recovery period after blood collection and influences that may arise from differences in the blood sampling site or blood sampling volume. We also summarized some perspectives on further implementation of microsampling in toxicology studies. The use of microsampling in regulatory toxicology studies has gradually increased, although at a lower rate than in discovery studies. Since more animals are used in GLP toxicology studies than in discovery studies, the effect of reducing the number of animals by microsampling is expected to be greater in the toxicology studies. This report aims to promote the application of microsampling to nonclinical studies, as it is beneficial for improving animal welfare and can contribute to the 3Rs.

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Assessment of haematological and clinical pathology effects of blood microsampling in suckling and weaned juvenile rats

Cited by 17 publications

References 5 publications

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Reducing blood volume requirements for clinical pathology testing in toxicologic studies—points to consider

Opportunities to Apply the 3Rs in Safety Assessment Programs

Impact of microsampling on toxicological evaluation in rodent safety studies

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