The in silico toxicology protocol consortium has been working on developing in silico protocols across various endpoints. While there are existing frameworks for identifying endocrine disrupting chemicals, there remains a lack of guidance on the usefulness and limitations of predicting relevant effects and mechanisms using in silico methodologies and how to combine relevant information inclusive of those generated by computational models. The endocrine activity working group has been 1) actively addressing which toxicological mechanisms or effects could be realistically predicted using in silico tools given data availability and the state of science around the endpoint, 2) identifying which in silico methodologies to use and 3) how to combine various lines of evidence from both experimental and computational approaches to derive an endpoint assessment.
A challenging area for the use of in silico methods in the context of predicting the endocrine disruption hazard of a chemical is the requirement identifying a mode of action linking the mechanistic activity of the substance with in vivo adverse effects. While in vivo experimental data allows this evaluation, it is challenging to develop in silico tools to predict reproductive and developmental effects with the granularity that is required to establish this causal link with high confidence. However, given adequate scientific understanding of the systems involved at the mechanistic level, the advance of experimental systems and building upon work carried out by the ToxCAST and Tox21 initiatives, the prediction of endocrine activity (mechanistic effects) using in silico tools is an achievable goal. Therefore, in silico methods play a role in aiding the interpretation of in vivo effects observed in experimental studies. In addition to discussing data integration, the group will lay out case-studies on how in silico tools could be used to facilitate regulatory decision making and chemical prioritization. Our monthly meetings have become something to look forward to.
If you would like to participate in the endocrine activity working group, please contact cjohnson@leadscope.com.