Retrospective Analysis of Triple Pack Studies for Dermal Absorption

Substances can cause acute systemic toxicity when absorbed through the skin. Dermal systemic toxicity is in turn driven by the ability of a substance to penetrate the skin. Dermal absorption can be estimated using the “triple pack,” a study design that combines in vivo rat, in vitro rat, and in vitro human data to calculate an estimated human dermal absorption factor.

To assess the feasibility of deriving a dermal absorption factor using only in vitro data, NICEATM and EPA conducted a retrospective evaluation of agrochemical formulations to compare the dermal absorption factors derived from each method (Allen et al. 2021). The dermal absorption factor derived from the human in vitro study was also compared to the dermal absorption factor generated from the triple pack approach. Absorption through in vitro human skin was found to be similar to or less than that observed in rat skin for all formulations. For most of the formulations evaluated:

  • The in vitro rat method generated a similar or higher dermal absorption factor value than the in vivo method.
  • The human in vitro method provided a similar or higher estimate of dermal absorption than the triple pack approach.

This analysis supports potentially using in vitro data alone for dermal absorption factor derivation for human health risk assessment of pesticides. While it is preferable to use data from human skin for human health risk assessments, human in vitro data are not always available. The analysis also demonstrated that estimates of dermal absorption based on in vitro rat data are at least as protective as in vivo rat data, and thus could also be considered adequate for use in establishing dermal absorption factors.