However, it is vital to critically question which toxicity-related questions can be answered by the data created using such exposome-scale HBM methods. This clearly depends on the investigated biological matrix and the chemical properties of a specific toxicant. Blood may be a suitable matrix to assess chronic contamination with persistent organic pollutants (e.g. PFAS), while for immediately metabolized and excreted compounds such as phthalates, bisphenols or parabens, the parent compounds are more of a proxy of acute-rather than chronic ingestion . For such chemicals that do not feature any persistent metabolites, longitudinal urinary analysis of the predominant phase-II metabolites over longer periods of time, either by a direct assessment or by the application of deconjugation, may be better suited to assess chronic and dynamic exposures. Moreover, the method does not yet include direct markers of biological effect. Consequently, we believe this work is of prime relevance in the area of exposure monitoring, rather than biological effect monitoring. This distinction needs to be stated clearly, as the former may be used to only find associations between disease development and exposure patterns. We encourage the generation of sufficiently large data sets by exposome-scale investigations to increase statistical power. Biomarkers of biological effect directly assesse the adverse effect of a xenobiotic. For many chemicals no specific biomarkers of effect have been defined as their multidimensional mechanisms (e.g. EDCs acting on multiple fronts in the hormonal system) are not fully elucidated. For adduct-forming toxicants (e.g. acrylamide, PAHs, PhIP or phytotoxins) the availability of analytical standards severely limits the inclusion of DNA-or protein conjugates to date.