Doucet, O., N. Garcia, and L. Zastrow. Impairment of the Barrier Function of Excised Human Skin and Reconstituted Epidermis Following Acute Pretreatments with Acetone/Ether. Perspectives in Percutaneous Penetration. 1998. 6A:42.

acetone - 00067-64-1; ether - 00060-29-7

In human skin, the lipids of the stratum corneum are mainly responsible for the epidermal barrier function. The integrity of this barrier can be disrupted following the topical application of organic solvents. This study was aimed at investigating whether the alterations of the barrier function observed, in vitro, in dermatomed normal human skin (NHS) could be reproduced in a human reconstituted epidermis model [REp]. Acetone/ether (A/E) was applied as an acute disrupting pretreatment for 3, 7, 15 or 30 min. onto NHS or REp surfaces and then wiped off. The influence of this pretreatment on the alteration in the barrier function was then assessed through measurement of the transepidermal water loss (TEWL) and quantification of the cutaneous permeability for one hydrophilic chemical, caffeine (CAF).

In NHS only a 30 min exposure to A/E induced a significant increase in TEWL (1.6-fold) compared to unpretreated samples (control). Similarly, neither 3 min. nor 7 min. pretreatments were able to significantly enhance the diffusion of CAF through NHS. However, following the 15 min. pretreatment, the permeability of NHS for CAF was 3-fold enhanced compared to unpretreated skin samples. Increasing the duration of the pretreatment to 30 min. induced a significant impairment of the NHS barrier since under these conditions the penetration of CAF was 6-fold higher than through the control.

In REp, irrespective of duration, the A/E applications did not significantly modify cell viability when assessed shortly after the pretreatment. Surprisingly, the TEWL values obtained for the control samples in the REp model were quite similar to those for NHS. The mean values were only slightly higher than in NHS, 11 and 3 g/m2.h, respectively. As in human skin, the A/E pretreatment induced a clear alteration of the skin barrier function. In REp, as in NHS, only a 30 min exposure to A/E was able to induce a significant (1.4-fold) increase of the TEWL. Conversely, with NHS even the shortest pretreatment with A/E (3 min.) significantly increased the diffusion of CAF through the skin culture model. Increasing the duration of the solvent exposure from 3 to 15 min. did not enhance the barrier disruption. In both NHS and REp the 30 min. pretreatment induced the greatest alteration of the barrier.

In spite of some discrepancies between the response of the REp model and NHS to barrier disruption these preliminary results suggested that this skin culture model might be of interest in predicting some of the alterations in the barrier function of normal human skin.