IN VITRO PERCUTANEOUS ABSORPTION USING THE MATTEK EPI-606X SKIN CONSTRUCT AND HUMAN SKIN.

The rates of absorption of chemicals in human skin can be modeled in the in vitro percutaneous absorption assay. Moreover, the impact of various vehicles on the permeation rates of chemicals can also be evaluated. The reference material, benzoic acid (BA), was prepared in two vehicles (acetone and petrolatum) and was tested in duplicate trials in an engineered human skin construct (EPI-606X, MatTek Corp.) and in ex vivo human skin. The methods used are based upon guidance by the US Food and Drug Administration, with the exception that absorption was evaluated at 3 hours after test material application. Tissues were mounted in flow-through diffusion cells (0.64 cm2 area) and qualified for barrier function by 3H2O passage, followed by a finite dose (9 µL) of 14C-labeled BA applied at 4 µg/cm2. The barrier function test was conducted by applying 200 µL of 3H2O onto the tissues for 20 minutes. Non-absorbed 3H2O was removed from the surface after 20 minutes, and the tissues were maintained for an additional 60 minutes in the diffusion cells. The amount of 3H2O absorbed into the receptor fluid was measured during the 80-minute test. Results of the barrier function tests showed that 1.71% ± 0.33 (n=16) and 0.36% ± 0.13 (n=6) of the applied 3H2O dose permeated through the engineered and human donor skin, respectively. Results of the percutaneous absorption of BA showed that in both skin models, the permeation rates for BA prepared in petrolatum were significantly higher than for BA prepared in acetone. At 3 hours, permeation rates for BA prepared in petrolatum were 80.9% and 51.9% of applied dose, for engineered skin and human skin, respectively (1.6 fold higher in engineered skin vs. human skin). Permeation rates for BA prepared in acetone were 38.1% and 12.5% of applied dose, for engineered skin and human skin, respectively (3.0 fold higher in engineered skin vs. human skin). These results show that both the engineered and human skin can be used to evaluate the impact of vehicles on the permeation rates of test chemicals.

3H2O, 3H2O passage, Acetone, BA, Barrier function, Barrier function test, Benzoic acid, EPI-606X, Engineered human skin construct, Engineered skin, EpiDerm, Ex vivo human skin, FDA, Flow-through diffusion cells, Human skin, In vitro percutaneous absorption assay, Percutaneous absorption, Permeation rate, Petrolatum, Rates of absorption, Receptor fluid, U.S. Food and Drug Administration