Genotoxicity assessment of two hypergolic energetic propellant compounds.
Recognition of the occupational hazards from exposure to the propellants hydrazine and monomethylhydrazine (MMH) has led to research into less toxic alternatives. Two hypergolic compounds, dimethylamino-2-ethylazide (DMAZ) and N,N,N',N'-tetramethylethanediamine (TMEDA), have been identified as possible replacements for MMH. We have obtained genotoxicity data for these compounds from in vitro and in vivo studies. DMAZ did not produce any mutagenic effects at concentrations up to 5mg/plate in the TA98 and TA1537 strains of Salmonella typhimurium and in an Escherichia coli (WP2 uvrA) strain, with or without metabolic activation, but did produce a positive response in the TA100 and TA1535 strains, both with and without metabolic activation. TMEDA was found not to be mutagenic in any of the bacterial strains tested (Salmonella TA98, TA100, TA1535, TA1537 and E. coli, WP2 uvrA), with or without metabolic activation. DMAZ did not induce structural chromosomal aberrations at levels up to 5mg/mL in Chinese hamster ovary (CHO) cells, with or without metabolic activation. TMEDA produced a positive response in this system, with or without metabolic activation, but only at the highest concentration, 5mg/mL. However, according to the OECD guideline TG 473, the compound is considered to be negative in the CHO chromosomal aberration assay, since the compound was not clastogenic at 0.01M (1.140mg/mL). DMAZ and TMEDA, when tested in vivo in the CD-1 mouse at doses up to 500 and 250mg/kg, respectively, did not induce micronuclei in bone marrow erythrocytes. These studies demonstrate that DMAZ is mutagenic in specific strains of Salmonella. However, both compounds were negative for induction of chromosomal aberrations in CHO cells in vitro and in the in vivo mouse micronucleus assay.
Reddy
Gunda
G
Directorate of Toxicology, U.S. Army Public Health Command (Provisional), 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403, USA.
Song
Jian
J
Mecchi
Michael S
MS
Johnson
Mark S
MS
D000818:Animals; D001386:Azides / Q000633:toxicity*; D001711:Biotransformation; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D003959:Diamines / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure; D012486:Salmonella typhimurium / Q000235:genetics
D001386:Azides; D003959:Diamines; D004785:Environmental Pollutants; D009153:Mutagens; C552125:N,N,N',N'-tetramethylethanediamine; C552124:dimethylamino-2-ethylazide