CATMoS: Collaborative Acute Toxicity Modeling Suite.

Area of Science:

• Toxicology
• Computational Chemistry
• Regulatory Science

Background:

• Chemicals require toxicity assessment for safety and regulation.
• Traditional rodent acute toxicity tests are costly and time-consuming.
• In silico models offer a faster, animal-free alternative for toxicity prediction.

Purpose of the Study:

• Develop in silico models for predicting acute oral toxicity.
• Address multiple toxicity endpoints including LD50 and hazard classifications.
• Facilitate regulatory decision-making through validated alternative methods.

Main Methods:

• Compiled an inventory of 11,992 chemicals for acute oral toxicity data.
• International collaboration involving 35 research groups developed 139 predictive models.
• Consensus models (CATMoS) were created by combining individual model predictions for enhanced accuracy.

Main Results:

• CATMoS demonstrated high accuracy and robustness in predicting acute oral toxicity.
• Consensus predictions leveraged the strengths of multiple individual in silico models.
• Validated predictions against in vivo results to ensure reliability.

Conclusions:

• CATMoS shows potential as a replacement for in vivo rat acute oral toxicity studies.
• CATMoS predictions are accessible through NTP's Integrated Chemical Environment and the open-source tool OPERA.
• In silico modeling advances chemical safety assessment and regulatory science.