Best practices for clinical pathology testing in carcinogenicity studies.

Area of Science:

• Veterinary Pathology
• Toxicologic Pathology
• Carcinogenicity Studies

Background:

• The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) formed a working group to establish best practices.
• Existing regulatory guidance and literature were reviewed, alongside a global survey of veterinary pathologists' current practices and recommendations.

Purpose of the Study:

• To recommend best practices for incorporating clinical pathology testing into carcinogenicity studies.
• To provide guidance on the appropriate use and limitations of clinical pathology in evaluating potential carcinogens.

Main Methods:

• Review of regulatory documents and scientific literature.
• Survey of veterinary pathologists across North America, Japan, and Europe.
• Consensus recommendations developed by a working group.

Main Results:

• For two-year rodent carcinogenicity studies, clinical pathology testing should be restricted to blood smears at sacrifice, examined only if hematologic neoplasia is suspected post-histopathology.
• Additional clinical pathology is recommended only for specific issues arising from prior toxicity studies or known test article effects.
• Insufficient data exist for recommendations on six-month genetically modified mouse carcinogenicity assays, though a similar approach to two-year studies is suggested.

Conclusions:

• Limited clinical pathology testing, primarily focused on blood smears for specific diagnostic needs, is recommended for standard carcinogenicity studies.
• The value of extensive clinical pathology in these studies is questioned, advocating for targeted application.
• Further research is needed to define the role of clinical pathology in alternative carcinogenicity models.