Effect of JP-8 jet fuel on molecular and histological parameters related to acute skin irritation

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 expos ure 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, a nd 6 h after the beginning of the exposures, homogenized, and analyzed for interleukin (IL)-1 alpha and inducible nitric oxide synthase (iNOS) protein and nitrite levels. IL-1 alpha levels (determined by ELISA) ranged from si milar to 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-1<alpha> were detecte d when compared to the 0-h samples. Western blot analysis revealed signific antly higher (p<0.05) levels of iNOS at 4 and 6 h compared to 0-h samples. Increases in IL-11<alpha> and iNOS expression were also observed in the ski n immunohistochemically. Nitrite concentrations in skin samples were measur ed to estimate nitric oxide production. Although nitrite concentrations in the skin increased similar to6-27% above the 0-h samples over the observed time period, no significant changes in nitrite levels were detected. Pathol ogical changes in the skin following JP-8 exposure were evaluated histologi cally. Increased numbers of granulocytes were observed infiltrating the ski n at 2 h and were more prominent by 6 h. These data show that a 1-h exposur e to JP-8 results in a loca inflammatory response, which can be detected by changes in molecular and histological parameters. (C) 2001 Academic Press.