In Vitro Rat Hepatocyte Toxicity and Bacteria Genotoxicity Evaluation of High Energy Chemicals for Replacement of Hydrazine

摘要

In an effort to develop methods to predict the toxicological response of newly synthesized chemicals that are of interest to the US Air Force, in vitro rat hepatocyte toxicity and bacteria (Salmonella) genotoxicity assays were performed on thirteen high-energy chemicals (HEC) that were selected as potential replacements of hydrazine. The HECs were primarily hydrazine derivatives (hydrazinium nitrate, HZN; 2-hydroxyethylhydrazine nitrate, HEHN; diethyl hydrazine nitrate, DEHN; 1,4- nitrate, DHTN; methylhydrazine nitrate, MHN; diaminogaanidine nitrate, DAGN; 2,2-dimethyltriazanium nitrate, DMTN; nitroaminogaanidine nitrate, NAGN), amino containing compounds (ethanolamine nitrate, EAN; histamine dinitrate, HDN; methoxylamine nitrate, MAN), and triazole containing compounds (1,2,-triazole nitrate, TN; 4-amino-l,2,4-triazole nitrate, ATN). The results in hepatocytes showed a dose dependent decrease in mitochondrial activity (MTT), increase in lactate dehydrogenase (LDH) leakage, and depletion of GSH levels. Responses to hydrazine were used as reference values for ranking the other HECs. According to the MTT assay, the hydrazine- containing compounds are the most toxic (HZN> DEHN> DHTN > MHN > HEHN > DAGN > NAGN), amino-containing compounds displayed medium toxicity (HDN > EAN > MAN) and triazole-containing compounds exhibited low toxicity (DMTN > ATN > TN). Results of genotoxicity (Ames assay) on 10 of the 13 HECs indicated that HZN, DHTN and MAN were mutagenic. DHTN was a direct mutagen causing AT and GC base- pair substitutions and frameshift mutations.