The absorption of aromatic hydrocarbons from aqueous media is a critical step involved in many biological processes after occupational and environmental exposures to jet fuel. A membrane-coated fiber (MCF) technique was used to study the uptake kinetics. A flow-through system was used to provide a constant concentration for the prolonged permeation experiments. Polydimethylsiloxane (PDMS) and polyacrylate (PA) MCFs were used to study the differential absorptivity of the aromatic compounds between the two membrane materials. The equilibrium absorption amount and a kinetic parameter describing the absorption kinetics were obtained by the regression of the permeation profiles of the aromatic compounds with a mathematical model. The partition coefficients, uptake, and elimination rate constants were determined for six benzene and three naphthalene derivatives. The PDMS/water partition coefficients of the benzene and naphthalene derivatives were linearly correlated with their logK(o/w) (LogK(pdms/w) = 0.871LogK(o/w) - 0.241, R(2) = 0.995). The PA/water partition coefficients of the benzene derivatives and the naphthalene derivatives were correlated differently with their logK(o/w). The correlation equations for benzene and naphthalene derivatives were LogK(pa/w) = 0.865LogK(o/w) + 0.0045, R(2) = 0.997 and LogK(pa/w) = 0.763LogK(o/w) + 0.911, R(2) = 1.00, respectively. These results suggest that the MCF technique can detect subtle differences in molecular interactions of the two group derivatives between the two membrane/water systems and may be used to study the absorption and permeation properties of closely related compounds. Finally, the regression method is a particularly useful tool to determine partition coefficients of very lipophilic compounds.
[Show abstract][Hide abstract] ABSTRACT: The focus of this research project was to characterize the nature of JP-8 toxicity to the skin and continue development of an in vitro model system, membrane coated fiber (MCEG) array, for assessing physiochemical parameters related to hydrocarbon partitioning and absorption through skin. In vitro studies with human epidermal keratinocytes demonstrated that inhibition of the NF-kB pathway with blockers confirms its role in cytokine production in jet fuel and hydrocarbon exposure in vitro. This could potentially reduce the inflammatory effect of fuel exposure in vivo. Exposure to the synthetic hydrocarbon fuel S-8 also is capable of inducing epidermal keratinocyte irritation in vitro as assessed by cytotoxicity and cytokine release. We have shown close correlation between MCF predicted dermal absorption of a series of compounds and measured permeability in skin. Patterns of aromatic hydrocarbon partitioning into three different MOE fibers (Polydimethylsiloxane, Polyacrylate, Carbowax) from three different vehicles (water, water/ethanol, biological albumin containing media) were different and could serve as a basis for clustering jet fuel hydrocarbon constituents in interpreting their patterns of absorption or biodistribution.
[Show abstract][Hide abstract] ABSTRACT: Jet fuel components are known to partition into skin and produce occupational irritant contact dermatitis (OICD) and potentially adverse systemic effects. The purpose of this study was to determine how jet fuel components partition (1) from solvent mixtures into diverse membrane-coated fibers (MCFs) and (2) from biological media into MCFs to predict tissue distribution. Three diverse MCFs, polydimethylsiloxane (PDMS, lipophilic), polyacrylate (PA, polarizable), and carbowax (CAR, polar), were selected to simulate the physicochemical properties of skin in vivo. Following an appropriate equilibrium time between the MCF and dosing solutions, the MCF was injected directly into a gas chromatograph/mass spectrometer (GC-MS) to quantify the amount that partitioned into the membrane. Three vehicles (water, 50% ethanol-water, and albumin-containing media solution) were studied for selected jet fuel components. The more hydrophobic the component, the greater was the partitioning into the membranes across all MCF types, especially from water. The presence of ethanol as a surrogate solvent resulted in significantly reduced partitioning into the MCFs with discernible differences across the three fibers based on their chemistries. The presence of a plasma substitute (media) also reduced partitioning into the MCF, with the CAR MCF system being better correlated to the predicted partitioning of aromatic components into skin. This study demonstrated that a single or multiple set of MCF fibers may be used as a surrogate for octanol/water systems and skin to assess partitioning behavior of nine aromatic components frequently formulated with jet fuels. These diverse inert fibers were able to assess solute partitioning from a blood substitute such as media into a membrane possessing physicochemical properties similar to human skin. This information may be incorporated into physiologically based pharmacokinetic (PBPK) models to provide a more accurate assessment of tissue dosimetry of related toxicants.
Journal of Toxicology and Environmental Health Part A 12/2007; 70(22):1879-87. DOI:10.1080/15287390701549146 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Water-to-polydimethylsiloxane (PDMS) and gas-to-PDMS sorption coefficients have been compiled for 170 gaseous and organic solutes. Both sets of sorption coefficients were analyzed using the Abraham solvation parameter model. Correlations were obtained for both "dry" headspace solid-phase microextraction and conventional "wet" PDMS coated surfaces. The derived equations correlated the experimental water-to-PDMS and gas-to-PDMS data to better than 0.17 and 0.18 log units, respectively. In the case of the gas-to-PDMS sorption coefficients, the experimental values spanned a range of approximately 11 log units.
Journal of Chromatography A 01/2008; 1175(2):162-73. DOI:10.1016/j.chroma.2007.10.058 · 4.17 Impact Factor
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