Mind the gaps: Prioritizing activities to meet regulatory needs for acute systemic lethality

Area of Science:

• Toxicology
• Computational Chemistry
• Regulatory Science

Background:

• Focuses on developing non-animal methods for characterizing acute systemic lethality.
• Discusses progress and needs in predicting acute oral lethality for chemicals and mixtures.
• Highlights the importance of understanding mechanisms of acute toxicity.

Discussion:

• A tiered approach integrating non-testing methods is recommended.
• Computational models and mixture assessments are viable for certain toxicity ranges.
• Transparency and understanding in vivo variability are key for regulatory acceptance.

Key Insights:

• Non-testing approaches like waiving tests and computational models can be applied now.
• Mathematical approaches for mixtures require policy development and refinement.
• Mechanistically based in vitro/in silico models are crucial for highly toxic substances.

Outlook:

• Immediate and near-term applications of new approaches are identified.
• Further actions are needed to fully replace animal use in acute toxicity testing.
• Continued research into in vitro and in silico models will support regulatory acceptance.