The Exposome and Toxicology: A Win-Win Collaboration

Abstract

The development of the exposome concept has been one of the hallmarks of environmental and health research for the last decade. The exposome encompasses the life course environmental exposures including lifestyle factors from the prenatal period onwards. It has inspired many research programs and is expected to influence environmental and health research, practices, and policies. Yet, the links bridging toxicology and the exposome concept have not been well developed. In this review, we describe how the exposome framework can interface with and influence the field of toxicology, as well as how the field of toxicology can help advance the exposome field by providing the needed mechanistic understanding of the exposome impacts on health. Indeed, exposome-informed toxicology is expected to emphasize several orientations including (1) developing approaches integrating multiple stressors, in particular chemical mixtures, as well as the interaction of chemicals with other stressors, (2) using mechanistic frameworks such as the adverse outcome pathways to link the different stressors with toxicity outcomes, (3) characterizing the mechanistic basis of long-term effects by distinguishing different patterns of exposures and further exploring the environment-DNA interface through genetic and epigenetic studies, and (4) improving the links between environmental and human health, in particular through a stronger connection between alterations in our ecosystems and human toxicology. The exposome concept provides the linkage between the complex environment and contemporary mechanistic toxicology. What toxicology can bring to exposome characterization is a needed framework for mechanistic understanding and regulatory outcomes in risk assessment.

Keywords: adverse outcome pathways; chemical toxicity; epigenetics; mixtures; multiple stress.

Figure 1.

Major features of exposome toxicology. The exposome concept is essentially multidisciplinary and has influenced several fields. This figure shows the different impact of the exposome concept on toxicology. AEP: aggregated exposure pathways; AOP: adverse outcome pathways.

Figure 2.

Multidisciplinary characterization of multiple stressor exposure and impacts. Exposure and epidemiological studies (including molecular epidemiology) can reveal associations between certain combinations of stressors and health outcomes. Based on these data, toxicological studies can analyze the involved mechanism and support causality. These studies can also be triggered by hypothesis put forward based on the scientific literature (eg, involvement of a common receptor for different stressors). Toxicological data together with those of population studies can support regulation and public health decisions.

Figure 3.

Linking exposures and effects: the triple A framework (AEP, absorption, distribution, metabolism, excretion, AOP). A major objective of environment and health studies is to link exposure and effect. The figure presents a framework connecting aggregated exposure pathways and AOP. The connection is at least partially mediated by the internal dose of contaminants which is governed by the ADME framework.