Skin absorption based on RHE models

The mechanistic principles for the uptake of chemicals into and through human skin and reconstructed human epidermis (RHE) are almost identical, the stratum corneum being the major barrier. Regarding morphology, immunohistochemistry and lipid composition RHE at current state is close to human epidermis. In addition, blood circulation does not play a role until the corium. In contrast to the skin of furry animals, in humans the shunt pathway of absorption via the hair follicles is of little relevance due to the low number. They are absent in RHE.

The endpoints assessed in the test method are the permeation of the respective test substance through RHE and skin into the receptor medium as quantified by cumulated amount, μg/cm² and %, after 6 and 24 h. Using the infinite dose approach (282.5 μ l aqueous solution of the test substance per cm² skin) permeation coefficient Papp (cm/s) and lag-time (h) as further endpoints are derived from the linear part of the respective absorption curves by linear regression. In addition, the finite dose approach (10 μl of the test substance per cm² skin) was used to quantify the penetration of the test substance into the skin.