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Comparative In Vivo Toxicity of Topical JP-8 Jet Fuel and Its Individual Hydrocarbon Components: Identification of Tridecane and Tetradecane as Key Constituents Responsible for Dermal Irritation

Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, North Carolina, USA

Correspondence: Address correspondence to: N. A. Monteiro-Riviere Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA; e-mail:NancyMonteiro{at}ncsu.edu

Despite widespread exposure to military jet fuels, there remains a knowledge gap concerning the actual toxic entities responsible for irritation observed after topical fuel exposure. The present studies with individual hydrocarbon (HC) constituents of JP-8 jet fuel shed light on this issue. To mimic occupational scenarios, JP-8, 8 aliphatic HC (nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane) and 6 aromatic HC (ethyl benzene, o-xylene, trimethyl benzene, cyclohexyl benzene, naphthalene, dimethyl naphthalene) soaked cotton fabrics were topically exposed to pigs for 1 day and with repeated daily exposures for 4 days. Erythema, epidermal thickness, and epidermal cell layers were quantitated. No erythema was noted in 1-day in vivo HC exposures but significant erythema was observed in 4-day tridecane, tetradecane, pentadecane, and JP-8 exposed sites. The aromatic HCs did not produce any macroscopic lesions in 1 or 4 days of in vivo exposures. Morphological observations revealed slight intercellular and intracellular epidermal edema in 4-day exposures with the aliphatic HCs. Epidermal thickness and number of cell layers significantly increased (p < 0.05) in tridecane, tetradecane, pentadecane, and JP-8-treated sites. No significant differences were observed in the aromatic HC-exposed sites. Subcorneal microabscesses containing inflammatory cells were observed with most of the long-chain aliphatic HCs and JP-8 in 4-day exposures. Ultrastructural studies depicted that jet fuel HC-induced cleft formation within intercellular lipid lamellar bilayers of the stratum corneum. The degree of damage to the skin was proportional to the length of in vivo HC exposures. These data coupled with absorption and toxicity studies of jet fuel HC revealed that specific HCs (tridecane and tetradecane) might be the key constituents responsible for jet fuel-induced skin irritation.

Key Words: Hydrocarbons • skin • in vivo irritation • jet fuel • ultrastructure • pathology

Abbreviations: NBF, 10% neutral buffered formalin • FTIR, Fourier Transform Infra Red • H&E, hematoxylin and eosin • HEK, human epidermal keratinocytes • HC, hydrocarbon • LM, light microscopy • SC/FTIR, Stratum Corneum/Fourier Transform Infra Red • TEM, transmission electron microscopy

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