New Publication: Quantitative Predictions for Molecular Initiating Events Using Three-Dimensional Quantitative Structure-Activity Relationships

This publication describes the latest progress in our collaboration with University of Cambridge in developing structural activity relationships at the molecular initiating event (MIE) level. Abstract: The aim of human toxicity risk assessment is to determine a safe dose or exposure to a chemical for humans. The molecular initiating event (MIE) is the first chemical interaction between a chemical toxicant and a biological molecule that can lead to adverse outcomes. Key chemical characteristics can be identified and used to model the chemistry of these MIEs. In this study, we do just this, by using chemical substructures to categorize chemicals and 3D quantitative structure-activity relationships (QSARs) based on comparative molecular field analysis (CoMFA) to calculate molecular activity. These models provide molecular activity estimation well within one log unit, and electronic and steric fields that can be visualized to better understand the MIE and biological target of interest. The outputs of these fields can be used to identify key aspects of a chemical’s chemistry which can be changed to reduce its ability to activate a given MIE. With this methodology, the quantitative chemical activity can be predicted for a wide variety of MIEs, which can feed into AOP-based chemical risk assessments, and understanding of the chemistry behind the MIE can be gained.

View the publication here.


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