Citation:

Nelms, M. Use of 2D chemical structure and bioactivity profiles to generate chemical categories within an Adverse Outcome Pathway network. American Chemical Society, New Orleans, Louisana, March 18 - 22, 2018.

Impact/Purpose:

This work covers how 2D chemical structure information and bioactivity profiles can be utilised to group chemicals, and how the inclusion of bioactivity profiles may help in the refinement of these chemical groupings for prioritisation and/or hazard/risk assessment.

Description:

The Adverse Outcome Pathway (AOP) framework has emerged to capitalise on the vast quantity of mechanistic data generated by alternative techniques, as well as advances in systems biology, cheminformatics, and bioinformatics. AOPs provide a scaffold onto which mechanistic data can be organised to establish a connection between a molecular initiating event (MIE) and an adverse outcome. The MIE is the initial interaction between chemical and biological systems. Understanding the details of this interaction between chemicals and biological molecules can help discern the structural and/or physico-chemical properties that may be required to perturb the MIE. This information can enable chemicals to be grouped based upon their ability to perturb an MIE using both structural and functional criteria such as a conserved structural fragment, in vitro activity connected to the MIE, and/or toxicological data connected to downstream key events in the AOP. Subsequently, the use of chemical groups, alongside information relating to the associated MIE/AOP(s), can be used for various applications. These include: hazard/risk assessment, prioritisation of chemicals for further testing, and/or identification of the AOP network(s) most likely to be of concern if chemicals co-occur within the environment. Upon development of chemical groups, data gap filling methods such as read-across can be used to provide predictions for chemicals within a chemical group that currently lack relevant toxicological data. This work covers how 2D chemical structure information and bioactivity profiles can be utilised to group chemicals, and how the inclusion of bioactivity profiles may help in the refinement of these chemical groupings for prioritisation and/or hazard/risk assessment. Additionally, this presentation will discuss how chemical categories can be used in conjunction with AOP networks to guide various aspects of mixtures risk assessment. This abstract does not reflect the views or policies of the EPA

Record Details: