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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Collaborative Acute Toxicity Modeling Suite (CATMoS) Tool for Predicting Acute Oral Toxicity

CATMoS is a free online resource for screening organic chemicals for acute oral toxicity.

The ICCVAM Acute Toxicity Workgroup organized a global project to develop in silico models of acute oral systemic toxicity that predict five specific endpoints needed by regulatory agencies:

  • Very toxic (LD50 <50 mg/kg vs. all others)
  • Nontoxic (LD50 >2000 mg/kg vs. all others)
  • LD50 point estimates
  • Hazard categories under the EPA classification system (n=4) 
  • Hazard categories under GHS (n=5; Category 5 and Not Classified combined into a single category)

NICEATM invited scientists to develop models to predict any or all of these endpoints. NICEATM and the EPA National Center for Computational Toxicology (NCCT; now part of the EPA Center for Computational Toxicology and Exposure) collected a large body of rat acute oral toxicity data. Subsets of these data were used by project participants to build and test their models, and by NICEATM and the project organizing committee to evaluate the models. Project participants and potential users of the models attended a workshop at NIH in Bethesda, Maryland, in April 2018 (Kleinstreuer et al. 2018).

Models developed for the project that met both quantitative and qualitative criteria defined by the project organizing committee were used to generate consensus predictions for the acute oral toxicity endpoints of interest to regulatory agencies. The consensus predictions are available in CATMoS, which is implemented in v2.5 of OPERA, a free and open-source QSAR tool (Mansouri et al. 2018). The consensus predictions will also be available via the Integrated Chemical Environment and EPA's CompTox Dashboard. A journal article in preparation for submission in 2020 will describe generation of the consensus predictions.