Organising data and knowledge to support the identification of chemicals with endocrine disruption potential
Presented by Emma Hill at the 2019 British Toxicology Society Annual Meeting.
The endocrine system regulates important bodily functions such as reproduction and sexual development through the secretion of hormones. Disruption of these systems can lead to a range of adverse health effects. EU agencies have published guidance on how to identify pesticides and biocides with endocrine disrupting properties, which is based on the WHO definition of an endocrine disruptor. This definition requires the chemical to cause an adverse outcome through disruption of the endocrine system. Therefore to complete these types of assessment, both toxicity and mechanistic data are required. However, relevant data are often stored in multiple repositories and are heterogeneous in nature.
Adverse outcome pathways (AOPs) provide a framework to integrate mechanistic knowledge with empirical data and predictive models. Therefore, centralising information in this manner will help ease the hindrance around data and knowledge retrieval. Database searches were performed and relevant endocrine modality assays were identified. The assays and their results were normalised, which included curation of chemical structures and annotations to define the assay protocols. Linear AOPs stemming from binding to the oestrogen receptor, androgen receptor and aromatase were synthesised and consolidated into an AOP network. Events in the AOP network could then be linked to relevant assays, their results and predictive models.
Organisation of the data in this manner can support a variety of initiatives, including model building and supporting risk assessors to evaluate relevant data from a pathway perspective.