Analytical challenges and opportunities in the study of endocrine disrupting chemicals within an exposomics framework.

Exposomics aims to measure human exposures throughout the lifespan and the changes they produce in the human body. Exposome-scale studies have significant potential to understand the interplay of environmental factors with complex multifactorial diseases widespread in our society and whose origin remain unclear. In this framework, the study of the chemical exposome aims to cover all chemical exposures and their effects in human health but, today, this goal still seems unfeasible or at least very challenging, which makes the exposome for now only a concept. Furthermore, the study of the chemical exposome faces several methodological challenges such as moving from specific targeted methodologies towards high-throughput multitargeted and non-targeted approaches, guaranteeing the availability and quality of biological samples to obtain quality analytical data, standardization of applied analytical methodologies, as well as the statistical assignment of increasingly complex datasets, or the identification of (un)known analytes. This review discusses the various steps involved in applying the exposome concept from an analytical perspective. It provides an overview of the wide variety of existing analytical methods and instruments, highlighting their complementarity to develop combined analytical strategies to advance towards the chemical exposome characterization. In addition, this review focuses on endocrine disrupting chemicals (EDCs) to show how studying even a minor part of the chemical exposome represents a great challenge. Analytical strategies applied in an exposomics context have shown great potential to elucidate the role of EDCs in health outcomes. However, translating innovative methods into etiological research and chemical risk assessment will require a multidisciplinary effort. Unlike other review articles focused on exposomics, this review offers a holistic view from the perspective of analytical chemistry and discuss the entire analytical workflow to finally obtain valuable results.