Effect of JP-8 Jet Fuel on Molecular and Histological Parameters Related to Acute Skin Irritation

Abstract

Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Chambers. Whole skin samples were collected at 0, 1, 2, 4, and 6 h after the beginning of the exposures, homogenized, and analyzed for interleukin (IL)-1α and inducible nitric oxide synthase (iNOS) protein and nitrite levels. IL-1α levels (determined by ELISA) ranged from ∼11 to 34% above the 0-h samples over the observed time period. At 1 and 2 h, significantly higher (p < 0.05) levels of IL-1α were detected when compared to the 0-h samples. Western blot analysis revealed significantly higher (p < 0.05) levels of iNOS at 4 and 6 h compared to 0-h samples. Increases in IL-1α and iNOS expression were also observed in the skin immunohistochemically. Nitrite concentrations in skin samples were measured to estimate nitric oxide production. Although nitrite concentrations in the skin increased ∼6–27% above the 0-h samples over the observed time period, no significant changes in nitrite levels were detected. Pathological changes in the skin following JP-8 exposure were evaluated histologically. Increased numbers of granulocytes were observed infiltrating the skin at 2 h and were more prominent by 6 h. These data show that a 1-h exposure to JP-8 results in a local inflammatory response, which can be detected by changes in molecular and histological parameters.