A Decision Tree for Acute Oral Toxicity: Implementing the Last Resort Requirement in Practice

Area of Science:

• Chemical safety assessment
• Toxicology
• Regulatory science

Background:

• Traditional acute oral toxicity (AOT) testing relies on animal methods, facing ethical concerns and scientific limitations.
• Regulatory adoption of non-animal alternatives for AOT is inconsistent due to a lack of structured guidance.

Purpose of the Study:

• To develop a science-based Decision Tree (DT) for AOT hazard identification.
• To align the DT with the OECD Integrated Approaches to Testing and Assessment (IATA) framework.
• To promote the use of non-animal methods in regulatory decision-making.

Main Methods:

• Developed a Decision Tree (DT) as a specific IATA.
• Integrated in silico tools, in vitro assays, and Weight of Evidence (WoE) strategies.
• Ensured a transparent, modular workflow for AOT hazard identification.

Main Results:

• The DT provides a structured workflow for AOT hazard identification.
• It supports regulatory decision-making, such as under REACH.
• It formalizes decision-making to reduce animal testing.

Conclusions:

• The developed DT facilitates the transition to non-animal approaches for AOT assessment.
• It bridges the gap between regulatory mandates and current practices.
• Supports improved chemical safety evaluations while minimizing animal use.