e-Resources to Revolutionise Toxicology: Linking Data to Decisions

Digital resources have become ubiquitous in the biological sciences. They hold the key to enhance and revolutionize how we understand and assess the hazards posed by new and existing chemicals ranging from drug molecules to nanoparticles. The last decade has seen an enormous growth in e-resources capturing data related to the toxicological effects of chemicals as well as easy access to predictive software making assessments of hazard based on chemistry alone. A key challenge has been to motivate a generation of scientists, who traditionally relied on animal testing, to move away from the previous paradigm to one that is centered around digital resources capturing biological responses at the molecular level. In order to rationalize biological responses upon exposure to a chemical, the ‘Adverse Outcome Pathway’ (AOP) concept was introduced. This concept has become the leading force to provide a framework to organize toxicological responses at different levels of biological organization, i.e. the molecular, cellular, organ, and individual level. The heart of the AOP is the capability to link the initial interaction of a chemical with its biological target(s), through the intermediary steps in the biological pathway to an adverse effect. AOPs are publicly available through e-infrastructure such as the AOP Knowledge Base (AOP-KB, https://aopkb.oecd.org/background.html).

In order to fully revolutionize toxicology, quantification of AOPs and AOP networks is required. Quantification allows prediction of effects in terms of potency, which is a key factor in risk assessment of chemical substances. Digital resources play a major role in this revolution for several reasons. They will efficiently enhance this area of science enriching current and future AOP development: crowdsourcing of data is required to bring individual AOPs to life through quantification. Software is needed to link individual AOPs into networks better replicating the complexity of the biological systems they are trying to represent. Quantitative AOPs and AOP networks need to be publicly accessible and built on existing and future open access digital resources. e-Infrastructure such as the AOP Knowledge Base is required to provide a platform in a user-friendly, open access environment to facilitate implementation of quantitative AOPs for chemical risk assessment in the 21st century.

This workshop aims to map out how and where digital resources can aid to revolutionize toxicology. More specifically, the workshop has the objectives to: a) identify how digital resources will enhance the AOP paradigm; and b) to develop four partial quantitative AOPs by utilizing currently available digital resources, providing better insight into data requirements including accessibility. The four partial quantitative AOPs, related to skin sensitization, liver toxicity, neurotoxicity and carcinogenicity, should be considered as case studies that will facilitate the evaluation of e-tools and e-infrastructure for developing quantitative AOPs. The workshop will provide a forum for experimentalists to meet with bioinformaticians and modellers and draft together an inventory of e-tools that facilitate the development of quantitative AOP frameworks using digital resources.