From the exposome to mechanistic understanding of chemical-induced adverse effects

Abstract

The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health.

Keywords: AOP; Exposome; Risk assessment; Systems biology; Systems chemistry; Systems toxicology.

Figure 1:

Multiple chemical exposures of the environment and their link via environmental media and the food chain to human exposure. Any type of exogenous chemical exposure will change the endogenous exposure, both of which will elicit effects on cellular toxicity pathways. The cellular level might serve as integrator to understand both, the pathways to adverse health outcomes as well as to ecosystem-level effects.

Figure 2:

Defining the exposome.

Figure 3:

Interface between the (eco)exposome (in red), the aggregate exposure pathway (AEP, green) and adverse outcome pathway (AOP, blue). The red dashed boxes represent chemical components of the exposome. The AEP/AOP concept allows one to disentangle key events and allocate them to steps from the source of exposure to adverse effects. The grey boxes indicate experimental methods to quantify the chemical components of the exposome and the biological components of the AOP. Figure partially adapted from (Teeguarden et al. 2016).

Figure 4.

(A) AOP for mixtures and (B) qAOP mixture modelling concept for similar action (adapted with permission from Vogs, C. and Altenburger, R. (2016). Time- Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach. Environmental Science & Technology, 50(14): 7770–7780. Copyright (2016) American Chemical Society.