The penetration of 2,3,7,8-tetrachlorodibenzo-p-dioxin into viable and non-viable porcine skin in vitro.
Freshly harvested, full thickness porcine skin was kept metabolically viable at 4 degrees C in a minimal essential medium for at least 48 h, as judged by the formation of lactate or 14CO2 from 14C-labeled glucose. In vitro topical exposure to the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 65 ng/cm2) for up to 1000 min did not affect the viability of skin. The penetration and distribution of TCDD into porcine skin was studied in an in vitro system under a variety of conditions, such as viability status, different vehicles or concentrations, or artificial removal of the stratum corneum. Loss of viability of the skin increased the rate of penetration of TCDD by about 60%. Removal of the stratum corneum to mimic lesioned skin increased the rate of dermal penetration of TCDD about 3-fold. The use of acetone as the vehicle, simulating dermal exposure to TCDD as a dust or from a volatile solvent, resulted in higher rates of penetration than the use of mineral oil as the vehicle, which simulates the situation of industrial accidents. The percentage of dose absorbed was independent of the dose of TCDD (65 or 6.5 ng/cm2) administered to the surface of skin. Rates of dermal penetration of TCDD ranged form 14 to 985 pg/cm2 skin per h, or 0.2-1.5% of the dose/h, depending on the conditions of exposure. These rates of penetration are comparable with results obtained by others in several other species, with both in vitro and in vivo systems including human skin in vitro. Full thickness porcine skin, viable or previously frozen, is therefore a valid in vitro model to estimate dermal penetration of TCDD in humans.
Weber
L W
LW
Section of Environmental Toxicology, GSF-Institut für Toxikologie, Neuherberg, Germany.
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008899:Mineral Oil / Q000494:pharmacology; D014677:Pharmaceutical Vehicles; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013552:Swine
D014677:Pharmaceutical Vehicles; D000072317:Polychlorinated Dibenzodioxins; D000096:Acetone; D008899:Mineral Oil