Around two-thirds of chronic human illnesses cannot be explained by genetics alone. The Lancet Commission on Pollution and Health estimates that 16% of global premature deaths are linked to pollution. It is now thought that humankind has surpassed the safe planetary operating space for introducing human-made chemicals into the Earth System.

Direct and indirect exposure to a myriad of chemicals, known and unknown, poses a significant threat to biodiversity and human health, from vaccine efficacy to the rise of antimicrobial resistance as well as autoimmune diseases and mental health disorders.

Extremely large

The number of chemical structures known to us is expanding exponentially; for example, the number of entries to the Chemical Abstracts Service registry has crossed the threshold of 100 million substances in 2015 and continues to grow. When including the natural chemicals and the transformation products of human-made chemicals (i.e. exposome chemical space), the number of possible unique structures becomes extremely large, estimated at over 10⁶⁰. Most of the exposome chemical space is unknown. In fact, even for the human-made chemicals less than 1% has been properly assessed.

Our current chemical management strategy is mainly based on manual chemical registration and/or experimental measurements of those chemicals in environmental and biological samples. Both approaches are extremely challenging, costly, and inherently passive or, at best, reactive. Additionally, we are completely unaware of the boundaries of our measurement techniques. In other words, a lack of detection does not at all mean an absence of the chemical. This has been proven repeatedly, with compounds such as DDTs and PFAS as well-known examples.

To tackle the complexity of the exposome chemical space a combination of data-driven and conventional approaches is needed. The concepts such as structure-based molecular networking and synthetic accessibility, borrowed from the field of drug discovery, could provide us with the much-needed tools for incorporating more transformation products into the existing chemical databases. This approach will generate new lists of chemicals of emerging concern (i.e. new suspect analytes) that could be used for the retrospective analysis of archived data.

Moreover, modeling strategies can shed light on what can be measured by our current analytical strategies and what highly relevant chemicals are being systematically overlooked. Ultimately, the combination of all these approaches should give us a better understanding of the exposome chemical space. Only with a comprehensively mapped exposome chemical space, can we — exposomics and environmental sciences community, regulators — avoid future chemical crises, protecting both human and environmental health.

Saer Samanipour is associate professor of analytical chemistry at the University of Amsterdam. This contribution is an adaptation of a dated 20 June 2024.