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

Arch Toxicol. 2022 Sep;96(9):2429-2445. doi: 10.1007/s00204-022-03320-3. Epub 2022 Jun 15.

Abstract

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.

Keywords: Dermal absorption; Exposure assessment; Pesticides; Plant protection products; Risk assessment; Simplified risk assessment.

MeSH terms

  • Food Safety
  • Humans
  • Pesticides* / toxicity
  • Risk Assessment
  • Skin Absorption
  • United States
  • United States Environmental Protection Agency

Substances

  • Pesticides