title: Mixture effects of JP-8 additives on the dermal disposition of jet fuel components.
abstract: Aliphatic and aromatic components in formulated jet fuels can cause occupational dermatitis. However, the influence of JP-8 performance additives (DIEGME, 8Q21, and Stadis450) on the dermal disposition of fuel components is not well understood. These additives are formulated with commercial Jet-A to form military JP-8 fuel. The purpose of this study is to assess the influence of these additives on the dermal disposition of marker aromatic and aliphatic components, naphthalene and dodecane, respectively. Porcine skin sections in an in vitro system were used to characterize chemical-biological interactions that modulate diffusion of jet fuel components and isolated perfused porcine skin flaps (IPPSFs) were used to evaluate diffusion in a viable skin model with an intact microvasculature. In these 5-h studies, Jet-A, Jet-A + DIEGME, Jet-A + 8Q21, and Jet-A + Stadis450, Jet-A + DIEGME + 8Q21, Jet-A + DIEGME + Stadis450, Jet-A + 8Q21 + Stadis450, and JP-8 mixtures were tested. In general, naphthalene absorption (0.76-2.39% dose) was greater than dodecane absorption (0.10-0.84% dose), while the IPPSFs alone demonstrated that dodecane absorption was significantly greater in JP-8 than in Jet-A. Synergistic interactions with 8Q21 + Stadis450 appear to enhance systemic absorption of either naphthalene or dodecane, while DIEGME + Stadis450 increased naphthalene (1.88% dose) and dodecane (2.02% dose) penetration into the skin and fat tissues of IPPSFs. These findings were supported by the fact that 8Q21 + Stadis450 significantly increased dodecane flux and permeability in porcine skin sections, but 8Q21 alone reduced marker diffusion in both membrane systems. Furthermore, dodecane is more likely than naphthalene to remain in the stratum corneum and skin surface at 5 h, and DIEGME mixtures played a significant role in skin and surface retention of both markers. In summary, the data suggest that various combinations of these three performance additives in JP-8 can potentially alter the dermal disposition of aromatic and aliphatic fuel components in skin. More importantly, products of two-factor interactions were not predictable from single-factor exposures and, by extension, cannot be extrapolated to three-factor interactions.
authors.affiliation: Center for Cutaneous Toxicology and Residue Pharmacology, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. Ronald_Baynes@ncsu.edu
authors.forename: R E
authors.initials: RE
authors.lastname: Baynes
authors.forename: J D
authors.initials: JD
authors.lastname: Brooks
authors.forename: K
authors.initials: K
authors.lastname: Budsaba
authors.forename: C E
authors.initials: CE
authors.lastname: Smith
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000473:Alkanes / Q000493:pharmacokinetics; D000818:Animals; D004357:Drug Synergism; D006838:Hydrocarbons / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007648:Kerosene; D009281:Naphthalenes / Q000493:pharmacokinetics; D010477:Perfusion; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000473:Alkanes; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D007648:Kerosene; D009281:Naphthalenes; C007548:n-dodecane; C031721:naphthalene