title: Comparative mixture effects of JP-8(100) additives on the dermal absorption and disposition of jet fuel hydrocarbons in different membrane model systems.
abstract: Jet fuel are complex mixtures of hydrocarbon fuel components and performance additives. Three different membrane systems, silastic, porcine skin and the isolated perfused porcine skin flap (IPPSF) were used to gain insight into the possible mechanism for additive interactions on hydrocarbon component absorption. Influence of JP-8(100) additives on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of hydrocarbon absorption, were evaluated using analysis of means (ANOM) and analysis of variance (ANOVA). This study indicated that the naphthalene absorption through silastic membrane was significantly different with JP-8 plus individual additives as compared to controls, i.e. JP-8 and JP-8(100). The porcine skin data indicated that neither individual nor combinations of additives affected naphthalene absorption. The third membrane system (IPPSF) showed that only MDA and BHT were important additives altering naphthalene absorption. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption. MDA significantly decreased dodecane absorption in skin flaps. All individual and combinations of two additives with JP-8 affected naphthalene and dodecane surface retention in silastic membrane. The IPPSF indicated that only 8Q405 is a significant modulator of surface retention for both marker hydrocarbons. The 8Q405 significantly reduced naphthalene contents in dosed silastic and skin indicating a direct interaction between additive and marker hydrocarbons. The MDA and BHT, which significantly retained naphthalene in the stratum corneum of porcine skin individually, led to a statistical decrease in its retention in the stratum corneum when in combination (MDA + BHT) suggesting a potential biological interaction. These observations demonstrate that the single membrane system may not be suitable for the final prediction of complex additive interactions in jet fuels. Rather a combination of different membrane systems may provide the insight to elucidate the possible mechanism for additive interactions. Finally, it is important to assess all components of a chemical mixture since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 700 Hillsborough Street, Raleigh, NC 27606, USA.
authors.forename: Faqir
authors.initials: F
authors.lastname: Muhammad
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000287:Administration, Topical; D000473:Alkanes / Q000493:pharmacokinetics; D000818:Animals; D002250:Carbon Radioisotopes; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D006838:Hydrocarbons / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D008954:Models, Biological; D009281:Naphthalenes / Q000493:pharmacokinetics; D012828:Silicones / Q000737:chemistry; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
chemical_list: D000473:Alkanes; D002250:Carbon Radioisotopes; D004129:Dimethylpolysiloxanes; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D008567:Membranes, Artificial; D009281:Naphthalenes; D012828:Silicones; C007548:n-dodecane; C031721:naphthalene; C013830:baysilon