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Dermal absorption values are used to translate external dermal exposure into potential systemic exposure for non-dietary risk assessment of pesticides. While the Environmental Protection Agency of the United States of America (US EPA) derives a common dermal absorption factor for active substances covering all related products, the European Food Safety Authority (EFSA) requests specific product-based estimates for individual concentrations covering the intended use rates. The latter poses challenges, because it disconnects exposure dose from applied dose in absorption studies, which may not be suitable in scenarios where concentration is not relevant. We analyzed the EFSA dermal absorption database, collected 33 human in vitro studies from CropLife Europe (CLE) companies, where ≥3 in-use dilution concentrations were tested, and 15 dermal absorption triple pack datasets. This shows that absolute dermal absorption correlates with absolute applied dose on a decadic logarithm-scale, which is concordant with the toxicological axiom that risk is driven by exposure dose. This method is radically different from the current European approach focused on concentrations and offers new insights into the relationship of internal and external exposure doses when utilizing data from in vitro studies. A single average dermal absorption value can be simply derived from studies with multiple tested concentrations, by calculating the y-intercept of a linear model on a decadic logarithm scale while assuming a slope of 1. This simplifies risk assessment and frees resources to explore exposure refinements. It also serves as a basis to harmonize dermal absorption estimation globally for use in exposure-driven risk assessments.

Currently, the standard approach to estimate systemic exposure of workers after contact with dried pesticide residues on crops during re-entry activities relies on using the highest identified dermal absorption value for aqueous spray dilutions. However, recent dermal absorption studies with dried residues and their respective in-use dilutions have shown that this is likely to significantly overestimate their dermal penetration potential and, thus, predicted systemic exposure. The choice of appropriate dose levels for these dermal absorption studies has not been defined. Moreover, actual skin loading during re-entry tasks may differ significantly from that achieved by applying a fixed volume of an aqueous dilution, which is the standard practice in generic dermal absorption studies. To address this, we propose an approach to dose setting for dried residue studies within the current European risk assessment framework. Skin loading for studies can be calculated from the existing exposure algorithms and by taking appropriate body surface areas into account. Thus, skin loading in studies will vary depending on the exact nature and duration of the task and the region of the body exposed, reflecting actual exposure scenarios.

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