The cytotoxicity of jet fuel aromatic hydrocarbons and dose-related interleukin-8 release from human epidermal keratinocytes

Many jet fuel aromatic hydrocarbons are known carcinogens with the ability to both readily penetrate the skin with high absorptive flux and cause skin irritation. In order to evaluate the in vitro cutaneous toxicity of individual aromatic hydrocarbons in jet fuels and their potential for inducing skin irritation, we evaluated the LD50, the highest non-cytotoxic (5% mortality) dose (HNTD), and interleukin-8 (IL-8) release activity of nine major jet fuel aromatic hydrocarbons in human epidermal keratinocytes (HEK). LD50 ranged from 1.8 mM (0.03%) for cyclohexylbenzene to 82.9 mM (0.74%) for benzene, with a rank order potency of cyclohexylbenzene >trimethylbenzene greater than or equal toxylene >dimethylnaphthalene >ethylbenzene >toluene >benzene. The HNTD values ranged from 0.1 mM (0.001%) for cyclohexylbenzene to 48.2 mM (0.43%) for benzene. Naphthalene and methylnaphthalene could not be ranked in this comparison since their concentrations, presented as percentage saturation, were not comparable to the others presented as solutes in solution. There was a dose-related differential response in IL-8 release at 24 h. Toluene, xylene, trimethylbenzene, cyclohexylbenzene and dimethylnaphthalene significantly decreased IL-8 release at the respective HNTDs, while IL-8 release did not continue to decrease, or significantly increased (cyclohexylbenzene and dimethylnaphthalene), at the LD50. IL-8 significantly increased with both doses of methylnaphthalene and naphthalene. The presence of hexadecane and mineral oil greatly attenuated the cytotoxicity elicited by individual aromatic hydrocarbons in HEK cells.