The cytotoxicity of volatile JP-8 jet fuel components in keratinocytes

In vitro models are being used to evaluate the toxic and irritating effects of JP-8, a kerosene-based jet fuel. JP-8 components are volatile, which makes in vitro studies difficult to evaluate dose-response relationships due to changes in chemical dosimetry caused by evaporation from the exposure medium. An in vitro approach testing volatile chemical toxicity that we have recently developed was used to evaluate the toxicity of the JP-8 components m-xylene, 1-methylnaphthalene (1-MN), and n-nonane in keratinocytes. Partition coefficients were measured and used to estimate the chemical concentration in the keratinocytes. The EC50 for m-xylene and 1-MN decreased significantly (P < or = 0.05) at 1, 2, and 4h. For n-nonane, no significant decreases in the EC50 values were observed over time; marginal cytotoxicity of n-nonane in keratinocytes was observed at 1h. Within 4h, about 75-90% of each volatile chemical was observed to be lost from the exposure medium when tissues were exposed in unsealed 24-well plates. This decrease resulted in significantly higher medium chemical concentrations needed to obtain EC50 values when compared to tissues exposed in sealed vials. This study demonstrates that chemical evaporation during in vitro exposures can significantly affect toxicological endpoint measurements. Ultimately, relating target cell chemical concentration to cellular responses in vitro could be used in determining an equivalent external dose using a biologically-based mathematical model.