title: Genotoxicity assessment of an energetic propellant compound, 3-nitro-1,2,4-triazol-5-one (NTO).
abstract: 3-Nitro-1,2,4-triazol-5-one (NTO) is an energetic explosive proposed for use in weapon systems, to reduce the sensitivity of warheads. In order to develop toxicity data for safety assessment, we investigated the genotoxicity of NTO, using a battery of genotoxicity tests, which included the Ames test, Chinese Hamster Ovary (CHO) cell chromosome aberration test, L5178Y TK(+/-) mouse lymphoma mutagenesis test and rat micronucleus test. NTO was not mutagenic in the Ames test or in Escherichia coli (WP2uvrA). NTO did not induce chromosomal aberrations in CHO cells, with or without metabolic activation. In the L5178Y TK(+/-) mouse lymphoma mutagenesis test, all of the NTO-treated cultures had mutant frequencies that were similar to the average frequencies of solvent control-treated cultures, indicating a negative result. Confirmatory tests for the three in vitro tests also produced negative results. The potential in vivo clastogenicity and aneugenicity of NTO was evaluated using the rat peripheral blood micronucleus test. NTO was administered by oral gavage to male and female Sprague-Dawley rats for 14 days at doses up to 2g/kg/day. Flow cytometric analysis of peripheral blood demonstrated no significant induction of micronucleated reticulocytes relative to the vehicle control (PEG-200). These studies reveal that NTO was not genotoxic in either in vitro or in vivo tests and suggest a low risk of genetic hazards associated with exposure.
authors.affiliation: U.S. Army Public Health Command, 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: Emily M
authors.initials: EM
authors.lastname: Lent
authors.forename: Lee C B
authors.initials: LC
authors.lastname: Crouse
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D005260:Female; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests / Q000706:statistics & numerical data; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C505897:3-nitro-1,2,4-triazol-5-one; D009574:Nitro Compounds; D014230:Triazoles