Variability of Spleen and Mesenteric Lymph Node in Control Cynomolgus Monkeys ( Macaca fascicularis) from Nonclinical...

Area of Science:

• Veterinary Pathology
• Toxicology
• Immunology

Background:

• Nonclinical safety studies utilize control animals to establish baseline parameters.
• Spleen and mesenteric lymph nodes (MLNs) are critical immune organs often examined in toxicology studies.
• Variability in these organs can complicate the interpretation of test article effects.

Purpose of the Study:

• To assess the variability of microscopic observations in spleen and MLN of control cynomolgus monkeys.
• To determine correlations between these observations and other study data.
• To inform the interpretation of immune system-related endpoints in nonclinical safety studies.

Main Methods:

• Analysis of microscopic findings and weight parameters from 478 control cynomolgus monkeys across 53 safety studies.
• Statistical assessment of variability within and among control groups.
• Identification of correlations between specific microscopic observations and spleen weight parameters.

Main Results:

• High variability observed in spleen weight parameters (absolute and relative) within and among control groups.
• Microscopic observation grades for spleen and MLN were also highly variable.
• Frequent spleen observations included germinal center changes (58%), acidophilic material (52%), and compound follicles (20%).
• Frequent MLN observations included eosinophil infiltrates (90%), germinal center changes (42%), and brown pigment (21%).
• Meaningful correlations (r² > 0.3) were limited to reticuloendothelial hyperplasia, malarial pigment, and spleen weight parameters.

Conclusions:

• Inherent variability in spleen and MLN parameters complicates the assessment of test article-related immune effects.
• Low animal numbers per group in routine studies further challenge interpretation.
• A careful, weight-of-evidence approach is necessary for evaluating immune system endpoints in monkey toxicology studies.