Description of Collaborative Activity: |
With the increasing number of chemicals to assess for acute oral systemic toxicity potential (LD50) and the lack of in vitro approaches, the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), Acute Toxicity Workgroup organized an international collaborative project to develop in silico models as alternatives to predict LD50 and bridge data gaps. Participants from 35 groups submitted a total of 139 predictive models built using a dataset of 11,992 chemicals split into training (75%) and evaluation sets (25%). Crowdsourced models were developed for five endpoints: LD50 value, EPA hazard categories, GHS hazard categories, very toxic (LD50 < 50 mg/kg), and non-toxic (LD50 > 2000 mg/kg). Predictions within the applicability domains of the submitted models were evaluated, then combined into consensus predictions based on a weight-of-evidence approach. The resulting consensus model, forming the Collaborative Acute Toxicity Modeling Suite (CATMoS), leverages the strengths and overcomes the limitations of individual modeling approaches. The consensus predictions are fully reproduceable and performed at least as well as independent replicate in vivo acute oral toxicity assays. The CATMoS consensus model is available via the free and open-source tool OPERA (Open Structure-activity/property Relationship App). |
Type of Collaborative Activity: |
Committee, Advisory Group, or Work Group
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