Penetration,distribution and kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro

The in vitro penetration of³H-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into human cadaver skin was studied at concentrations of 65 and 6.5 ng TCDD per cm² of skin surface. Vehicles used were acetone to simulate exposure to TCDD as a dry material, and mineral oil to simulate exposure to TCDD in an oily medium. Penetration was performed for 30, 100, 300, and 1000 min in improved Franz cells. Skin was used either intact, or with stripped horny layer. Skin was sectioned along its natural layers and radioactivity determined in epidermis and dermis. TCDD did not readily penetrate into human skin in vitro. The vehicle of exposure to TCDD played an important role in dermal penetration. The rapidly evaporating acetone allowed TCDD to penetrate deeply into the loose surface lamellae of the horny layer, but then appeared to be poorly available for further penetration. Mineral oil as the vehicle, on the other hand, represented a lipophilic compartment which competed with lipophilic constituents of the stratum corneum for TCDD and hence slowed its penetration even more. The stratum corneum acted as a protective barrier, as its removal increased the amount of TCDD absorbed into layers of the skin. Hourly rates of absorption of TCDD per unit area of skin were calculated in two ways: a worst case scenario where TCDD absorbed into any layer of skin including the stratum corneum was used for regression analysis; and a physiological approach where only that amount of TCDD was considered absorbed which had penetrated beyond the epidermis into the region of dermal vascularization. Under worst case scenario conditions the stratum corneum appeared to mediate dermal absorption of TCDD, since calculated rates of absorption decreased when skin stripped of its stratum corneum was exposed to TCDD. This was, however, not the case with the physiological approach. There was a consistent relationship between concentration of TCDD applied and concentration of TCDD found in skin. Also, a clear-cut correlation was found between the amount of TCDD that penetrated and the time of exposure. The rate of penetration into intact skin of different concentrations of TCDD from acetone ranged from 100 to 800 pg TCDD per hour and cm² of skin (worst case scenario), or 6 to 170 pg per hour and cm² with the physiological approach. With mineral oil as the vehicle the rate of penetration into intact skin was lower, ranging from 20 to 220 pg and 1.4 to 18 pg, respectively, per hour and cm² of skin. Our results on the distribution of TCDD in human skin also suggest that as yet unknown constituents of epidermis and upper dermis have a somewhat higher affinity towards TCDD than those of the lower dermis.Presented in part at the 28th Annual Meeting of the Society of Toxicology, Atlanta, GA, 1989