Adequacies and inadequacies in assessing murine toxicity data with antineoplastic agents

Area of Science:

• Toxicology
• Pharmacology
• Oncology

Background:

• Retrospective analyses indicated a strong correlation between mouse and human toxic doses of antineoplastic agents.
• Recent toxicological data reveal significant variability in this correlation, challenging previous assumptions.

Purpose of the Study:

• To analyze the variability in toxic dose levels of antineoplastic agents between mice and humans.
• To highlight the importance of understanding factors contributing to interspecies differences in toxicity.

Main Methods:

• Accumulation and analysis of additional toxicological data.
• Retrospective review of existing toxic dose information.

Main Results:

• Identified noticeable variability in the toxic dose data base between mice and humans.
• Confirmed that mouse toxicological studies are likely to remain a principal determinant for estimating human doses.

Conclusions:

• Despite variability, mouse toxicological studies remain essential for preclinical dose estimation.
• Recognizing factors influencing interspecies toxicity differences will improve the predictive value of mouse models for human drug development.