title: Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN).
abstract: Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic toxicity of these compounds was evaluated to predict the potential adverse human health effects from exposure by using a standard genetic toxicity test battery which included: a gene mutation test in bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome aberration test and an in vivo mouse micronucleus test. The results of the Ames test showed that EDDN increased the mean number of revertants per plate with strain TA100, without activation, at 5000μg/plate compared to the solvent control, which indicated a positive result. No positive results were observed with the other tester strains with or without activation in Salmonella typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA. DETN was negative for all Salmonella tester strains and E. coli up to 5000μg/plate both with and without metabolic activation. The CHO cell chromosome aberration assay was performed using EDDN and DETN at concentrations up to 5000μg/mL. The results indicate that these compounds did not induce structural chromosomal aberrations at all tested concentrations in CHO cells, with or without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1 mouse at doses up to 2000mg/kg, did not induce any significant increase in the number of micronuclei in bone marrow erythrocytes. These studies demonstrate that EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other strains, for in vitro induction of chromosomal aberrations in CHO cells, and for micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in all in vitro and in vivo tests. These results show the in vitro and in vivo genotoxicity potential of these chemicals.
authors.affiliation: Army Institute of Public Health, Aberdeen Proving Ground, MD, USA. Gunda.reddy@us.army.mil
authors.forename: Gunda
authors.initials: G
authors.lastname: Reddy
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Paul
authors.initials: P
authors.lastname: Kirby
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000235:genetics; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D006801:Humans; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D011073:Polyamines / Q000633:toxicity*; D011759:Pyrrolidines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D009153:Mutagens; D011073:Polyamines; D011759:Pyrrolidines; C005391:diethylenetriamine; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine