Development of an in vitro model for determining the fate of chemicals applied to skin.
An in vitro apparatus was developed to determine the evaporation and percutaneous penetration of radiolabeled chemicals applied to pig skin. The dermal side of the skin was mounted on a penetration cell. Appearance of radioactivity in the fluid flowing past the dermal side of the skin indicated percutaneous penetration. An evaporation manifold, with replaceable vapor traps, was mounted on the stratum corneum side of the skin. Using the model, the influence of a number of factors (storage conditions, flow rate and composition of fluid in the penetration cell, and temperature and humidity of air flowing through the evaporation manifold) on the disposition of chemicals on the skin was determined. The percutaneous penetration and evaporation of N,N-diethyl-m-toluamide were determined on skin samples immediately after excision and after a freezing period of 1 to 6 weeks at -80 degrees C. Progressively greater percutaneous penetration values were associated with samples which had the greater storage times. Thereafter, only fresh skin was used. When the penetration cell flow was increased from 5 to 10 ml/hr of Tyrodes solution, or when porcine serum was substituted for Tyrodes solution as the fluid flowing through the penetration cell, no significant difference was found in total percutaneous penetration of several control compounds. However, total percutaneous penetration of N,N-diethyl-m-toluamide more than doubled when the air temperature was increased from 20 to 32 degrees C, whereas total evaporation decreased. Increasing the humidity of air flowing through the evaporation manifold enhanced the percutaneous penetration of polar organic compounds but had little effect of the percutaneous penetration of highly lipid soluble organic compounds. Using the model under standardized conditions, the percutaneous penetration of 10 control compounds (N,N-diethyl-m-toluamide, benzoic acid, caffeine, three steroids, and four insecticides) were found to correlate with the corresponding published values for man (r = 0.77, p = 0.05). The skin disposition of the nerve agent analog (diisopropylfluorophosphate, DFP) and simulant (diethyl malonate) was determined using the model. When applied to the skin at a dose of 0.1 mg/cm2, DFP and diethyl malonate were lost from the skin surface mainly by evaporation. Skin penetration was limited due to loss by evaporation.
D000818:Animals; D004347:Drug Interactions; D006813:Humidity; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000378:metabolism; D008314:Malonates / Q000378:metabolism; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013552:Swine; D013696:Temperature
D008314:Malonates; D004364:Pharmaceutical Preparations; D007531:Isoflurophate; C030978:diethylmalonic acid