Penetration, distribution and kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro.
The in vitro penetration of 3H-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
L W
LW
Weber
A
A
Zesch
K
K
Rozman
D004817:Epidermis / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014018:Tissue Distribution
D000072317:Polychlorinated Dibenzodioxins