Principles for the selection of doses in chronic rodent bioassays. ILSI Risk Science Working Group on Dose Selection

Area of Science:

• Toxicology
• Risk Assessment
• Pharmacokinetics

Background:

• Dose selection for chronic rodent bioassays has been a contentious issue in risk assessment.
• Previous attempts to establish consensus, like the 1993 National Research Council report, were unsuccessful.
• The traditional reliance on maximum tolerated dose (MTD) based on body weight and histopathology is being re-evaluated.

Purpose of the Study:

• To present a consensus set of principles for dose selection in chronic rodent bioassays.
• To encourage a shift from MTD-based selection to a more scientifically robust approach.
• To outline recommendations for international harmonization of dose selection procedures.

Main Methods:

• Development of consensus principles by the ILSI Risk Science Institute.
• Emphasis on utilizing sound toxicologic principles for dose selection.
• Integration of human exposure considerations and data from prechronic studies.

Main Results:

• A consensus has been reached on a set of principles for dose selection in chronic rodent bioassays.
• The new principles advocate for a comprehensive approach considering multiple toxicological endpoints and factors.
• The consensus moves away from sole reliance on the traditional definition of MTD.

Conclusions:

• The newly established principles provide a framework for scientifically sound dose selection in rodent bioassays.
• Implementation of these principles is expected to enhance the quality and consistency of bioassays globally.
• International harmonization of dose selection procedures is a key anticipated benefit.