In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory Impairment
Interim rept. Apr-Sep 2014
HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE WRIGHT-PATTERSON AFB OH
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Laboratory studies in rats support the potential for jet fuel to promote noise induced hearing loss NIHL. Occupational studies indicate that pilots, aircrew, and aircraft maintenance workers suffer higher rates of hearing loss. Jet fuel toxicity in association with noise may be at least partially explained by increased free radical production and oxidative stress at the cellular level. The project goal is to develop a multi-scale model to physiologically and mechanistically describe jet fuel exacerbated NIHL. This report describes the first five months of an ongoing effort. A pharmacodynamics PD model has been developed which describes the potential combined effect of jet fuel and noise on hearing loss via production of free radicals in cochlea hair cells. The PD model will be parameterized using results from in vitro studies. Initial proteomic studies with HEI-OC1 cells, a conditionally immortalized organ of Corti-derived epithelial cell line, indicate that JP-8 produces little cytotoxicity. Preliminary dose-response studies using the same cell type again revealed marginal cytotoxic effects when exposed to JP-8 or key hydrocarbons found in JP-8 and associated with chemically-induced hearing loss toluene, ethylbenzene, xylene, nonane, or decane. However, apoptosis and necrosis were enhanced when cells were exposed to JP-8 or hydrocarbons with oligomycin in vitro noise surrogate. The PD model is designed to interface with a physiologically-based pharmacokinetic PBPK model which will simulate delivery of JP-8 to the cochlea and other tissues during exposure.
- Anatomy and Physiology
- Medicine and Medical Research