REACH assessment of humans exposed to chemicals indirectly via the environment: screening modeling in EUSES versus state of the science.

The assessment of humans indirectly exposed to chemicals via the environment (HvE) is an assessment element of the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation. The European Union System for the Evaluation of Substances (EUSES) is the default screening tool, aimed at prioritizing chemicals for further refinement/higher tier assessment. This review summarizes the approach used in EUSES, evaluates the state of the science in human exposure modeling via the environment, and identifies areas for further research to strengthen the confidence and applicability of EUSES for assessing HvE. It confirms that EUSES v2.2 does serve as a conservative screening tool for identifying potential human risk due to HvE (via consumption of crops, meat and milk, fish, drinking water, and inhalation). However, certain submodels within EUSES have not been updated for at least two decades. For example, for highly soluble or highly hydrophobic or ionized organic substances, substance parameters are estimated based on outdated predictive models. We recommend to also update the REACH Technical Guidance to highlight possible refinements in HvE assessments as well as the integration of measured and (bio)monitoring data. Addressing limitations in the EUSES applicability domain, particularly for highly soluble and highly hydrophobic organic substances and ionized organics, would improve its applicability. We identified that some HvE submodels in EUSES could be readily updated to improve screening-level assessment in EUSES. In addition, updating the EUSES "food basket" using recent European Union food consumption data is crucial to accurately reflect recent dietary trends. Further research is required for prediction of leaf crop and drinking water exposure to better reflect the fate of chemicals in the environment. In particular for ionizable substances, research focused on QSAR (Quantitative Structure Acitivity Relationship) development and experimental measurement of fate properties is necessary to enhance the confidence of EUSES assessments.