Alternative mouse models for carcinogenicity assessment: industry use and issues with pathology interpretation

Area of Science:

• Toxicologic Pathology
• Genetically Modified Mouse Models
• Carcinogenicity Testing

Background:

• Industry practices and opinions on alternative mouse models for carcinogenicity testing were surveyed.
• The Carcinogenicity Alternative Mouse Models (CAMM) Working Group of the Society of Toxicologic Pathology (STP) conducted the survey.

Purpose of the Study:

• To define current industry practices and opinions on using alternative mouse models for carcinogenicity testing.
• To identify challenges and develop recommendations for the implementation and interpretation of these models.

Main Methods:

• A survey was distributed to members of the Society of Toxicologic Pathology.
• Results were analyzed to identify common practices, regulatory acceptance, and challenges associated with CAMM.

Main Results:

• CAMM are primarily used to meet regulatory requirements, replacing the two-year mouse bioassay and gaining regulatory acceptance.
• The p53+/- and rasH2 models are most common, with rasH2 being widely accepted for general carcinogenicity testing.
• Challenges include lack of historical data, unexpected tumor findings, pathology evaluation, animal numbers, survival, and study duration.

Conclusions:

• CAMM are a viable alternative to traditional carcinogenicity testing, with growing regulatory acceptance.
• Recommendations focus on standardizing positive control testing, histopathologic examination, diagnostic criteria, and historical data utilization.
• Further development and use of genetically modified mice in carcinogenicity testing are encouraged.