Chemical Safety and the Exposome

Abstract

Air pollution and rapid chemical intensification are major threats to the environment and human health. Today, we have produced over 350,000 chemicals, and current testing strategies do not meet the demands. Therefore, it is important to develop new approach methodologies (NAMs) that can help fill current information gaps. Toxicology needs to evolve from hazard and risk assessments based on morphological endpoints in animal tests towards a mechanism-driven integrated approach that better includes computational modelling as well as molecular, human, and in vitro data. The application of new science and technology such as different types of imaging and omics methods can allow faster collection of high-quality toxicological data for hazard identification and better prediction of toxicological potential using advanced in silico approaches including machine learning. A shift toward active prevention of pollution through a safe and sustainable-by-design approach based on cutting-edge science could significantly help safeguard the population and planetary health. Moreover, it is necessary to improve the understanding of how interactions among chemical mixtures, climate change, infectious agents, and other stressors that constitute the exposome, may affect biota and human health. Individual responses to current exposures and susceptibility to disease are influenced by factors such as genetics, epigenetics, physiology, and health status, which involve changes in biological pathways caused by previous exposures or even ancestral exposures. It is therefore important to better consider individual exposomes and susceptibility in future risk assessments and precision medicine. This review describes the central role of mechanistic toxicology in chemical safety and in the cross-disciplinary efforts needed to characterize the exposome and its complex interactions in detail.

Keywords: Anthropocene; Biodiversity; Chemicals; Environmental health; Epigenetics; Exposome; Mechanistic toxicology; One Health; Planetary health; Pollution.

Figure 1. Gene-environment interactions underlie the majority of chronic human diseases The exposome can be defined as the cumulative lifetime environmental exposure and related biological responses of an individual.

The individual response to current exposure and susceptibility to disease is influenced by factors such as genetics, epigenetics, physiology, and health status, which involve changes in biological pathways caused by previous exposures, or even ancestral exposures. Currently, there are more than 350,000 manmade chemicals, and the potential adverse effects of most of these are still poorly understood. Mechanistic toxicology will therefore play a fundamental role in the large cross-disciplinary efforts needed to better understand how complex exposome interactions may affect the biota and human health.