Variable hepatocellular vacuolization associated with glycogen in rabbits.

Area of Science:

• Toxicology
• Histopathology
• Animal Models

Background:

• Hepatocellular vacuolization is a common finding in rabbit liver studies.
• Variability in this finding can impact toxicity assessments.
• Glycogen accumulation is a primary cause of hepatocellular vacuolization.

Purpose of the Study:

• To investigate the variability of hepatocellular vacuolization in control rabbits.
• To identify factors influencing the degree of vacuolization.
• To emphasize the importance of recognizing this variation in toxicity testing.

Main Methods:

• Utilized New Zealand white rabbits in 28-day and 91-day percutaneous studies across five laboratories.
• Assessed hepatocellular vacuolization using light microscopy with a 5-grade histologic system.
• Corroborated subjective grading with quantitative measurements of hepatocyte perimeter and lobule radius.

Main Results:

• Significant variation in hepatocellular vacuolization was observed between laboratories and within studies.
• Females, higher body weight, increased relative liver weight, and specific laboratories were associated with increased vacuolization.
• Periodic acid-Schiff (PAS)-positive material, removable by diastase, confirmed glycogen presence in vacuoles.

Conclusions:

• Marked variability in hepatocellular vacuolization, primarily due to glycogen, is inherent in control rabbit studies.
• Factors such as sex, body weight, relative liver weight, and study laboratory significantly influence vacuolization.
• Recognizing this glycogen-related vacuolization is crucial for accurate interpretation of rabbit toxicity data.