Molecular event mapping opens door to more tests “in silico”

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Molecular event mapping opens door to more tests “in silico”

“Scientists report a new method for establishing whether chemical compounds are safe for human use without ‘in vivo’ testing, based on so-called “molecular initiating events” at the boundary between chemistry and biology.

If we can map the adverse outcome pathways of numerous molecules in the way that we have here, we will be able to develop models which mean you don’t have to administer products in vivo and then look for a reaction to establish whether or not they are safe. – Tim Allen

A new approach to mapping and predicting the impact of chemical compounds in the body, which it is hoped could eventually reduce the need for toxicity tests in animals, has been trialed by scientists.

Although still at an early stage, the process involves identifying ‘molecular initiating events’ (MIEs) – the term given to the moment at which a molecule that has entered the body starts to interact with it, kick-starting a sequence of events which leads to a toxic outcome.

By identifying the specific features and properties within individual molecules that cause these events, the researchers argue that it should be possible to make accurate predictions about the effects of new and untested chemical compounds with similar characteristics.

In principle, that would reduce the need to test some chemicals contained within drugs, pesticides, food additives or other consumer products on animals. Instead, scientists would be able to screen a chemical’s molecular structure using customised computer software – a transition they characterise as one from testing ‘in vivo’ (within the living) to ‘in silico’ (on computers).

To prove the point, the new research, reported in the journal Chemical Research in Toxicology, mapped the pathways by which several well-known compounds, such as paracetamol, cause toxic outcomes. By tracing these back to the molecular initiating event, the team were able to identify chemical characteristics, that were present in other molecules exhibiting the same toxicities. …

The research paper also speculates that better knowledge of Molecular Initiating Events could enable scientists to predict not only adverse, but also positive, outcomes which may emanate from the uptake of certain chemical compounds into the human body. The aim of the work, however, is firmly based in toxicology – to build on current in silico approaches, and increase understanding of what goes on during a toxic response. …”

Read the rest of this research news release from the University of Cambridge here:

The abstract is available here:

Allen, T.E., Goodman, J.M., Gutsell, S., & Russell P.J. (2014). Defining molecular initiating events in the adverse outcome pathway framework for risk assessment. Chem. Res. Toxicol. [Epub ahead of print].

Posted: December 3, 2014