Dermal Absorption

Skin penetration is an important element of predicting toxicity associated with topically applied substances. NICEATM and ICCVAM agencies are evaluating alternatives to animal tests for measuring dermal absorption.

Retrospective Analysis of Dermal Triple Pack Data

Substances can cause acute systemic toxicity when absorbed through the skin. Acute 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 (DAF).

To assess the feasibility of deriving a DAF using only in vitro data, NICEATM and EPA conducted a retrospective evaluation of agrochemical formulations to compare the DAF derived from each method (Allen et al. 2021). The DAF derived from the human in vitro study was also compared to the DAF 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 DAF 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.

While it is preferable to use data from human skin for human health risk assessments, human in vitro data are not always available. This analysis 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. Accordingly, this analysis supports potentially using in vitro data alone for DAF derivation for human health risk assessment of pesticides.

Data for analysis described in Allen et al. (2021)