title: Skin toxicity of jet fuels: ultrastructural studies and the effects of substance P.
abstract: Topical exposure to jet fuel is a significant occupational hazard. Recent studies have focused on dermal absorption of fuel and its components, or alternatively, on the biochemical or immunotoxicological sequelae to exposure. Surprisingly, morphological and ultrastructural analyses have not been systematically conducted. Similarly, few studies have compared responses in skin to that of the primary target organ, the lung. The focus of the present investigation was 2-fold: first, to characterize the ultrastructural changes seen after topical exposure to moderate doses (335 or 67 microl/cm2) of jet fuels [Jet A, Jet Propellant (JP)-8, JP-8+100] for up to 4 days in pigs, and secondly, to determine if co-administration of substance P (SP) with JP-8 jet fuel in human epidermal keratinocyte cell cultures modulates toxicity as it does to pulmonary toxicity in laboratory animal studies. The primary change seen after exposure to all fuels was low-level inflammation accompanied by formation of lipid droplets in various skin layers, mitochondrial and nucleolar changes, cleft formation in the intercellular lipid lamellar bilayers, as well as disorganization in the stratum granulosum-stratum corneum interface. An increased number of Langerhans cells were also noted in jet fuel-treated skin. These changes suggest that the primary effect of jet fuel exposure is damage to the stratum corneum barrier. SP administration decreased the release of interleukin (IL)-8 normally seen in keratinocytes after JP-8 exposure, a response similar to that reported for SP's effect on JP-8 pulmonary toxicity. These studies provide a base upon which biochemical and immunological data collected in other model systems can be compared.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27606, USA. Nancy_Monteiro@NCSU.edu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Inman
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D006801:Humans; D006838:Hydrocarbons / Q000633:toxicity; D016209:Interleukin-8 / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*; D007648:Kerosene / Q000633:toxicity*; D008854:Microscopy, Electron; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*; D013373:Substance P / Q000276:immunology / Q000494:pharmacology*; D013552:Swine
chemical_list: D006838:Hydrocarbons; D016209:Interleukin-8; C098607:JP8 aviation fuel; D007648:Kerosene; D013373:Substance P; C029662:JP5 jet fuel