Epidermal Barrier and Depot Function Changes from Xylene Exposure in the Perfused Pig Ear Organ Culture System

Abstract

Factors influencing the rate of dermal permeation of xylene were studied in vitro using the perfused pig ear (PPE) model. Pig-ear skin was exposed to xylene for either 3 ± 5 min (each period separated by 55 min), 15 min, 30 min, 60 min, or 240 min. Total permeation of xylene during this period was 23.2 ± 5.5 μg (n = 5), 29.7 ± 4.0 μg (n = 5), 28.2 ± 6.4 μg (n = 6), 48.1 ± 10.4 (n = 6), and 65.6 ± 8.3 μg (n = 6) respectively (mean ± SEM). There were no statistical differences in total permeation for exposure periods of 30 min or less and for 60 min or longer. However, the amount of xylene present in the skin was directly related to exposure time (15 min, 30 min, and 60 min). When skin was stripped (Scotch adhesive tape, 10 times) before being exposed to xylene for 15 min, total permeation increased by about twofold to 67.9 ± 15.6 μg (n = 3). In contrast, tape stripping after the 15 min exposure period resulted in a small decrease in the total amount of xylene permeating (22.3 ± 3.9 μg, n = 4). Epidermal damage appeared to be related to total exposure time (i.e., 3 ± 5 min resulted in similar damage to 1 ± 15 min). Stripping before exposure to xylene exacerbated the dermatotoxic effects of xylene. Our data indicate that dermal penetration, but not the rate of dermal permeation, is directly proportional to exposure time; alterations in permeation rate are associated with the dermatotoxic effects of xylene; the stratum corneum and the epidermis are both barriers to xylene; xylene forms reservoirs in the skin even after short exposures; and the dermis is important as a reservoir only after permeation through the epidermis is no longer rate limiting.