US EPA

2800961 

Technical Report 

Pharmacokinetic Manipulation and Modeling of the Trigger for JP-8- Induced Skin Irritation 

Mcdougal, JN 

2009 

NTIS/01320024 

GRA and I 

GRA and I 

Dermal exposure to JP-8 has been shown to cause skin irritation in humans and laboratory animals. We have previously investigated the early responses of mammalian skin to liquid JP-8 contact. We have developed a novel in vivo rat model for the investigation of skin irritation, which maintains the interactions and crosstalk of the wide variety of cells in the epidermis and dermis. We have used this model to investigate early gene expression with brief exposures to JP-8 and related skin irritants in both rats and humans. Our studies suggest that the 'trigger' of the JP-8 irritant response may be a 'physical' response that causes activation of signaling pathways that result in an inflammatory cytokine cascade as well as a competition between cell growth and apoptosis. We found that neither of four JP-8 components tested (2 aromatic and 2 aliphatic) exactly mimicked the JP-8 effects and that there were only minimal differences in gene expression between JP-8 and the synthetic fuel, S- 8. Our similar studies in volunteers showed that the human variability was very large, but that the responses of the most sensitive volunteers were very similar to the rat responses.