| Estimation of penetration rates of compounds through skin is an important for assessment of either the efficacy of a topical formulation, its irritation potential, or its potential systemic exposure. Current risk assessment models often assume that 100% of the applied dose is absorbed through the skin. This thesis provides experimental data to validate and calibrate a working diffusion/evaporation model for topically applied chemicals based on their physicochemical properties, the known biological properties of skin and principles of diffusion theory.; Four compounds with varying physicochemical properties were studied under different conditions---benzyl alcohol (BA), diethyl-m-toluamide (DEET), tecnazene and malathion. Absorption of 14C-BA, a perfume ingredient, was studied at different doses (0.9 mug/cm2 - 10.6 mg/cm 2) through human cadaver skin and silicone membrane. The disposition of BA was satisfactorily described by the diffusion model using a variable diffusivity coefficient.; The absorption and evaporation of the insect repellent 14C-DEET (127 mug/cm2) was characterized at airflows ranging from 10--100 mL/min. The amount of DEET absorbed through the skin systematically decreased as the airflow increased.; For tecnazene, a fungicide, and malathion, an insecticide, a Head space Solid Phase Micro Extraction technique was developed to analyze the receptor fluid following skin penetration experiments. The analysis was done using GC-MS.; Absorption rate of tecnazene, was studied following application of 103 mug/cm 2 and 864 mug/cm2 under open and occluded conditions. The absorption was much higher under occlusion and the overall recovery was also better for the occluded treatment.; Additionally disposition of topically applied 14C-malathion (101, 0.5 and 0.1 mug/cm2) was studied under open and occluded conditions and compared to GC-MS results from 101 mug/cm2. A silicone membrane study was performed with all three doses of 14 C-malathion.; The model satisfactorily described the absorption of malathion and tecnazene through human skin in vitro. Key parameters that needed modification were kevap (evaporation mass transfer coefficient), Ksc (partition coefficient of the stratum corneum, SC) and P sc (permeability of SC). Future work entails conducting partitioning studies of lipophilic compounds to get better understanding of disposition of such compounds in the lower skin layers. |
