JP-8 is the major jet fuel used by US Army and Air Force. The purpose of the present study was to investigate the percutaneous absorption of JP-8 across pig ear skin and human skin in vitro and to study the effect of JP-8 exposure on the skin barrier function and irritation in Yucatan minipigs. JP-8 spiked with 5.0 microCi of radiolabeled (14C)
tridecane,
nonane,
naphthalene or
toluene (selected components of JP-8) was used for the in vitro percutaneous absorption studies with excised pig ear skin and human skin. For in vivo studies, 250 microl of JP-8 or two of its components (
toluene or
nonane) was placed in a Hill top chamber(R) and affixed over the marked treatment area for 24 h. Transepidermal water loss (TEWL), skin capacitance (moisture content) and skin irritation (
erythema and
edema) were evaluated before treatment and at 1,2 and 24 h after removal of the patches. The components of JP-8 such as
tridecane,
nonane,
naphthalene and
toluene permeated significantly through pig ear skin and human skin and the permeation rates were found to be proportional to their composition in JP-8. The steady state flux values of
tridecane across pig ear skin and human skin did not differ significantly (P>0.05). Though the steady state flux values of
nonane,
naphthalene and
toluene were statistically different between porcine and human skin (P<0.01), the values were close considering the large variations usually observed in the percutaneous absorption studies. Application of
toluene,
nonane or JP-8 increased the TEWL, JP-8 being the highest (3.5 times at 24 h compared to baseline level). The skin moisture content decreased after the application of JP-8, though it was not significantly different (P>0.05) from the baseline level. JP-8 caused a moderate
erythema and a moderate to severe
edema. Though the
edema decreased after 24 h, the degree of
erythema remained about the same until 24 h. The skin irritation caused by JP-8 was greater than neat
toluene or
nonane. The TEWL data of
toluene,
nonane and JP-8 correlated well with the skin irritation data (
erythema and
edema). Exposure of JP-8, which contains hundreds of aliphatic and
aromatic hydrocarbons, caused significant changes in the barrier function of the skin as indicated by an increase in TEWL and produced a significant
erythema and
edema in minipigs. Furthermore, the disruption of barrier function of skin, as indicated by increased TEWL after exposure to JP-8 might result in increased permeation of its own components and/or other chemicals exposed to skin. The present study provides further evidence that pig ear skin may be used as a model for predicting the rates of permeation of chemicals through human skin.