The transient dermal exposure: theory and experimental examples using skin and silicone membranes.
J Pharm Sci 2008 Apr; 97(4):1578-1592
A diffusion model is presented to account for the disposition of chemicals applied to skin as transient exposures. Two conditions are considered that apply to the skin surface following the exposure period, which are applicable to chemicals exhibiting two extremes of chemical volatility. For one case, representing highly volatile compounds, the solution is generalized to apply to multiple transient exposures. For both cases, algebraic expressions are derived to calculate the total amount of chemical that penetrates the skin. The theory is applied to experimental measurements of the in vitro penetration of diethyl phthalate applied to hairless guinea pig (HGP) skin and silicone rubber membranes (SRMs) as transient exposures. The transient exposure theory ably models the experimental data, with coefficients of determination greater than 0.97 (HGP) and greater than 0.99 (SRM). The ability of parameters derived from concurrent infinite dose experiments to predict the time course of absorption from transient exposures is explored. Discrepancies were found between measured cumulative penetration of chemical from transient exposure experiments and penetration predicted from parameters derived from infinite dose experiments, particularly for HGP. Possible reasons are explored. The current model may provide a realistic framework for estimating absorption from occupational, environmental and pharmaceutical dermal exposures.
Mathematical-models; Skin; Skin-absorption; Skin-irritants; Skin-sensitivity; Diffusion-analysis; Laboratory-animals; Dose-response; Models
H. Frederick Frasch, Health Effects Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505
Journal of Pharmaceutical Sciences