Topical absorption and toxicity studies of jet fuel hydrocarbons in skin

Kerosene-based fuels have been used for many decades. Over 2 million military and civilian personnel each year are occupationally exposed to various jet fuel mixtures. Dermatitis is one of the major health concerns associated with these exposures. In the past, separate absorption and toxicity studies have been conducted to find the etiology of such skin disorders. There was a need for integrated absorption and toxicity studies to define the causative constituents of jet fuel responsible for skin irritation. The focus of this thesis was to study the percutaneous absorption and to identify the hydrocarbons (HC) causing irritation in jet fuels so that preventive measures could be taken in the future.; The initial study was conducted to understand the possible mechanism for additive interactions on hydrocarbon absorption/disposition in silastic, porcine skin and isolated perfused porcine skin flap (IPPSF) models. The influence of JP-8 (100) additives (MDA, BHT, 8Q405) on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of HC absorption was evaluated. This study indicated that individual and combination of additives influenced marker disposition in different membranes. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption in IPPSF. The 8Q405 significantly reduced naphthalene content in dosed silastic and skin indicating a direct interaction between additive and marker HC. Similarly, the individual MDA and BHT significantly retained naphthalene in the stratum corneum of porcine skin, but the combination of both of these additives statistically decreased the marker retention in the stratum corneum suggesting a potential biological interaction. This study concluded that all components of a chemical mixture should be assessed since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture. However, this study indicated that the marker HC absorption was similar across JP-8 and JP-8 (100) due to the opposite effects of MDA and BHT on HC absorption.; The remaining studies were focused on neat HC absorption and toxicity potential in pig skin. There were no published reports regarding dose-related percutaneous absorption of jet fuel HC that are crucial for risk assessment studies. Three dosing mixtures (1X, 2X, and 5X) comprising 5 aliphatic (C11--C15) and 2 aromatic (naphthalene and dimethyl naphthalene (DMN)) HC were dosed using in vitro porcine skin flow-through diffusion cells with hexadecane as the diluent. Perfusate samples were analyzed with gas chromatography flame ionization detector (GC-FID) using a headspace solid phase micro-extraction (SPME) fiber technique. (Abstract shortened by UMI.)...