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Paper: A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non‐dietary risk assessment of pesticides

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Authors: Felix M. Kluxen · Edgars Felkers · Steve McEuen · Philip Fisher · Christian Strupp · Christine Lorez · Jeanne Y. Domoradzki · Christiane Wiemann

CropLife Europe’s proposal for a new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides was just published. We can derive average dermal absorption values from in vitro studies, which simplifies risk assessment and frees resources for better exposure estimation and is a proposed alternative to the current regulatory approach.

Dermal absorption values are used to translate external dermal exposure into potential systemic exposure for non-dietary risk assessment of pesticides. In Europe, one risk assessment assumption is that dermal absorption, expressed as percentage penetration of the applied dose, increases with dilution. While this can be sometimes observed in in vitro dermal absorption studies, it is conflicting with basic toxicological assumptions, namely, that risk is driven by dose, and physiological properties of dermal absorption as described by Fick’s laws. Further, exposure models usually consider dose and not concentration, and other exposure scenarios, for example, exposure to dried residues, are not appropriately modelled by the default study designs.

One key observation of the current project was that applied dose and absolute amount absorbed seem to better characterize dermal absorption properties than concentrations and relative amount penetrated. This allows the derivation of an average relative dermal absorption value from dermal absorption studies conducted with multiple concentrations. Thus, exposure calculations can be tremendously simplified as potential systemic exposure depends only on exposure dose and not assumed and hypothetical exposure concentration.