The investigators propose to develop a sophisticated, yet accessible mathematical model that closely mimics percutaneous penetration, tissue concentrations and clearance in human skin in vivo. This development will significantly advance the mechanistic understanding of allergic and irritant dermatitis and the mechanics of dermal exposure assessment. This objective will be accomplished through the construction and experimental verification of physiological and physical properties-based models for percutaneous absorption incorporating features not found in the mathematical models presently used to estimate dermal exposure. Successful completion of the specific aims of the proposal will lead to the following: (1) an experimentally verified, microscopic model of transport in human stratum corneum and skin appendages (hair follicles, sweat glands); (2) a dermal vascular model that allows accurate predictions of permeant concentrations and clearance in the viable skin layers; (3) a transient diffusion model for calculating dermal absorption subsequent to low-to-moderate exposures to potentially volatile compounds; (4) a skin hydration model for linking the above with steady-state permeability models presently in use; and (5) an easy-to-use spreadsheet for dermal exposure calculations incorporating the most important features from the investigation. The research methods include: Sophisticated numerical techniques for modeling transport in heterogeneous structures and advanced graphical representation of these results. Detailed examination of stratum corneum ultra structure and microtransport properties using laser scanning confocal microscopy, fluorescence photobleaching,and other light microscopic techniques. Determination of diffusivities and partition coefficients of selected permeants in stratum corneum, epidermis, dermis, and hypodermis and the role of protein binding on these values.

National Institute of Health (NIH)
National Institute for Occupational Safety and Health (NIOSH)
Research Project (R01)
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Safety and Occupational Health Study Section (SOH)
Program Officer
Robison, William
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University of Cincinnati
Schools of Pharmacy
United States
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Li, Xin; Johnson, Robert; Kasting, Gerald B (2016) On the Variation of Water Diffusion Coefficient in Stratum Corneum With Water Content. J Pharm Sci 105:1141-7
Gajjar, Rachna M; Kasting, Gerald B (2014) Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions. Toxicol Appl Pharmacol 281:109-17
La Count, Terri D; Kasting, Gerald B (2013) Human skin is permselective for the small, monovalent cations sodium and potassium but not for nickel and chromium. J Pharm Sci 102:2241-53
Gajjar, Rachna M; Miller, Matthew A; Kasting, Gerald B (2013) Evaporation of volatile organic compounds from human skin in vitro. Ann Occup Hyg 57:853-65
Dancik, Yuri; Miller, Matthew A; Jaworska, Joanna et al. (2013) Design and performance of a spreadsheet-based model for estimating bioavailability of chemicals from dermal exposure. Adv Drug Deliv Rev 65:221-36
Ibrahim, Rania; Nitsche, Johannes M; Kasting, Gerald B (2012) Dermal clearance model for epidermal bioavailability calculations. J Pharm Sci 101:2094-108
Ibrahim, Rania; Kasting, Gerald B (2012) Partitioning and diffusion of parathion in human dermis. Int J Pharm 435:33-7
Kissel, John C (2011) The mismeasure of dermal absorption. J Expo Sci Environ Epidemiol 21:302-9
Miller, Matthew A; Kasting, Gerald B (2010) Toward a better understanding of pesticide dermal absorption: diffusion model analysis of parathion absorption in vitro and in vivo. J Toxicol Environ Health A 73:284-300
Kasting, Gerald B; Miller, Matthew A; Bhatt, Varsha D (2008) A spreadsheet-based method for estimating the skin disposition of volatile compounds: application to N,N-diethyl-m-toluamide (DEET). J Occup Environ Hyg 5:633-44

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