IN VITRO AND IN VIVO COMPARISON OF DERMAL IRRITANCY OF JET FUEL EXPOSURE USING EPIDERM (EPI-200) CULTURED HUMAN SKIN AND HAIRLESS RATS.

This study by researchers at the Schools of Pharmacy at Florida A&M University and Auburn University demonstrated that MatTek’s EpiDerm human skin tissue equivalent can be used as an alternative to animals in evaluating the dermal irritation potential of several jet fuel formulations. The purpose of this study was to evaluate the EpiDerm™ in vitro human skin model (EPI-200) to study the irritation potential of jet fuels (JP-8 and JP-8+100). Parallel in vivo studies on hairless rats on the dermal irritancy of jet fuels were also conducted. Cytokines are an important part of an irritation and inflammatory cascade, which are expressed in upon dermal exposures of irritant chemicals even when there are no obvious visible marks of irritation on the skin. Researchers chose two primary cytokines (IL-1α and TNF-1α) as markers of irritation response of jet fuels. Initially, the EpiDerm EPI-200 was treated with different quantities of JP-8 and JP-8+100 to determine quantities which did not cause significant cytotoxicity, as monitored using the MTT assay and paraffin embedded histological cross-sections. Volumes of 2.5–50 µl/tissue (∼4.0–78µl/cm2) of JP-8 and JP-8+100 showed a dose dependent loss of tissue viability and morphological alterations of the tissue. At a quantity of 1.25µl/tissue (∼2.0µl/cm2), no significant change in tissue viability or morphology was observed for exposure time extending to 48 h. Nonetheless, this dose induced significant increase in IL-1α and TNF-α release versus non-treated controls after 24 and 48 h. In addition, IL-1α release for JP-8+100 was significantly higher than that observed for JP-8, but TNF-α release after 48 h exposure to these two jet fuels was the same. These findings parallel in vivo studies on hairless rats, which indicated higher irritation levels due to JP-8+100 versus JP-8. In vivo, transepidermal water loss (TEWL) and IL-1α expression levels followed the order JP-8+100 > JP-8 > control. Further, in vivo TNF-α levels for JP-8 and JP-8+100 were also elevated, but not significantly different from one another. In aggregate, these findings indicate that the EpiDerm EPI-200 tissue model can be utilized as an alternative to the use of animals in evaluating dermal irritation.

Cytokines, Dermal exposures, Dermal irritancy, EPI-200, EpiDerm human skin model, Hairless rats, Histological cross-sections, IL-1a, Inflammation, Inflammatory, Inflammatory cascade, Irritant chemicals, Irritation potential, Irritation response of jet fuels, JP-8, JP-8+100, Jet fuel, MTT, MTT assay, Skin irritancy, Skin irritation, TNF-1a, Transepidermal water loss (TEWL)