In vitro toxicity assessment of a new series of high energy compounds

Hydrazine is an aircraft fuel and propellant used by the US Air Force. Due to its toxicity the Propulsion Directorate of the Air Force Research Laboratory ŽAFRL PR. has investigated alternative chemicals to replace hydrazine. AFRL PR has synthesized a series of high energy chemicals ŽHECs., primarily hydrazine derivatives and amino containing compounds such as hydrazinium nitrate ŽHZN., 2-hydroxyethyl-hydrazine nitrate ŽHEHN., diethyl hydrazine nitrate ŽDEHN., ethanolamine nitrate ŽEAN., histamine dinitrate ŽHDN. and methoxylamine nitrate ŽMAN. to study as alternative chemical candidates. Although HECs are reliable constituents of powered propellant systems, they constitute an important class of toxic agents to which military and civilian personnel can be exposed. The current study was undertaken to examine the toxicity of HECs in primary hepatocytes in vitro. The effects of short-term exposure Ž4 h. of hepatocytes to HECs were investigated with reference to viability, mitochondrial function and oxidative stress markers. The results showed a decrease in mitochondrial activity, increase in lactate dehydrogenase ŽLDH. leakage and depletion of reduced glutathione ŽGSH. levels. The levels of reactive oxygen species ŽROS. increased dose dependently in HZN, MAN and HDN exposed cells. However, there was no induction of ROS generation in EAN, DEHN and HEHN exposed cells. Depletion of GSH in hepatocytes by buthionine sulfoximine ŽBSO. prior to exposure to HZN increased its toxicity. The results suggest that at least one mechanism of HEC toxicity is mediated through oxidative stress.