The exposome - a new paradigm for non-animal toxicology and integrated risk assessment

There is an urgent need for cheaper, faster and mechanism-based approaches in toxicology. Despite major advances in the fields of biotechnology, molecular biology and information technology, the fundamental premises of toxicology have not changed over the last several decades. Today, companies and agencies still largely use animal studies to assess toxicological risk, although they are costly (more than 4 billion € worldwide) and too slow to provide answers to the complex toxicological questions posed. In-depth safety assessment of a pesticide amounts to €20 million and five years requiring 2kg of a chemical not yet in production. This has led to the current lack of toxicological information, which is required to safeguard human health and regulatory decision making on chemicals, lately shown to exceed 350,000 in commercial use world-wide. Toxicologists have become increasingly aware of these limitations and have brought forward new approaches to overcome them. The National Research Council vision report on Toxicity Testing in the 21st Century (Tox-21c) of 2007, now principally forming the novel toxicity-testing paradigm, suggests moving to a pathway-based testing strategy away from traditional animal–based methods, which are too slow for testing large numbers of chemicals or combinations thereof in mixtures. Towards this pathway-based approach, human exposome studies provide an interesting alternative, able to accelerate the transition to non-animal based hazard assessment for chemical risk assessment. The aim of this chapter, is to demonstrate how this is feasible, taking stock of recent advances in human exposome analysis, as well as in vitro, non-mammalian in vivo, cross-omics and in silico methods (including biokinetics, bioinformatics, systems biology and adverse outcome pathways). To consolidate the paradigm change, the proposed methodology is demonstrated in the case of developmental neurotoxicity (DNT) and developmental immunotoxicity (DIT) assessment