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A scheme to evaluate structural alerts to predict toxicity - Assessing confidence by characterising uncertainties
Mark T D Cronin1, Franklin J Bauer2, Mark Bonnell3
1School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Regulatory Toxicology and Pharmacology : RTP
|August 30, 2022
Summary
This study introduces a new framework with twelve criteria to evaluate the confidence of structural alerts in silico toxicology. This system helps assess alert reliability for regulatory and industrial applications.
Area of Science:
- Toxicology
- Computational Chemistry
- Regulatory Science
Background:
- Structure-activity relationships (SARs) are crucial for in silico toxicology, forming the basis of structural alerts.
- Currently, no formal process exists to assess the confidence associated with these structural alerts.
- Existing in silico methods lack a standardized approach for evaluating alert confidence.
Purpose of the Study:
- To propose a formal process for assessing the confidence of structural alerts.
- To develop twelve criteria for evaluating the uncertainty associated with structural alerts.
- To enable a more robust assessment of structural alert reliability in toxicological evaluations.
Main Methods:
- Developed twelve criteria focusing on alert purpose, chemical and toxicological details, mechanism, performance, coverage, and supporting evidence.
- Applied these criteria to assess the confidence and uncertainty of structural alerts.
- Evaluated the proposed scheme within industrial and regulatory use case contexts.
Main Results:
- A scheme with twelve criteria was established for confidence assessment of structural alerts.
- Alerts can now receive a confidence score, highlighting areas needing further investigation.
- The evaluation scheme identified distinct alert characteristics, such as specificity and generality.
Conclusions:
- The proposed criteria provide a formal method for assessing structural alert confidence in toxicology.
- This confidence assessment aids in identifying suitable applications for alerts, like read-across and hazard identification.
- The scheme supports informed decision-making in industrial and regulatory toxicology by clarifying alert reliability.
Keywords:
Computational toxicologyConfidenceEvaluation schemeStructural alertStructure-activity relationshipToxicity predictionUncertaintyUse caseMore Related Videos
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