title: Testicular effects of 3-nitro-1,2,4-triazol-5-one (NTO) in mice when exposed orally.
abstract: 3-Nitro-1,2,4-triazol-5-one (NTO) is currently being investigated in the development of insensitive munitions. Rats orally exposed to NTO have demonstrated testicular toxicity in both subacute and subchronic studies; however, toxicity has not been verified in mice. Also, previous studies have not demonstrated the nature of NTO-induced testicular toxicity due to the prolonged dosing regimen utilized and effects of maturation depletion. In this study, a time-course design was used and the earliest pathological changes in testes of adult BALB/c mice orally dosed with NTO in corn oil suspensions at 0, 500 or 1000 mg/kg-day NTO for 1, 3, 7 or 14 d were evaluated. The earliest NTO-induced testicular changes occurred in the 1000 mg/kg-day group at day 7 and the 500 mg/kg-day group at day 14 as evident by the presence of bi- and multinucleated giant cells (MNGCs) of almost all spermatids in an isolated stage II-III tubule/step 2-3 and a stage IX tubule/step 9 in the 1000 and 500 mg/kg-day groups, respectively. Testicular toxicity was characterized by degeneration and the presence of bi- and MNGCs of spermatids (stages II-III and IX), which progressed to additional germ cell degeneration as dosing duration increased. Occasional step 16 spermatid retention was also noted in stage XII and I tubules in the day 14, 1000 mg/kg-day group. These data indicate that NTO is a testicular toxicant in mice and that spermatids are the most sensitive cell. The presence of retained spermatids warrants further investigation regarding NTO's role as a direct Sertoli cell toxicant.
authors.affiliation: a Veterinary Services Program, Walter Reed Army Institute of Research/Naval Medical Research Center , Silver Spring , MD , USA and.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Mullins
authors.affiliation: a Veterinary Services Program, Walter Reed Army Institute of Research/Naval Medical Research Center , Silver Spring , MD , USA and.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Despain
authors.affiliation: a Veterinary Services Program, Walter Reed Army Institute of Research/Naval Medical Research Center , Silver Spring , MD , USA and.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallace
authors.affiliation: a Veterinary Services Program, Walter Reed Army Institute of Research/Naval Medical Research Center , Silver Spring , MD , USA and.
authors.forename: Cary L
authors.initials: CL
authors.lastname: Honnold
authors.affiliation: b U.S. Army Public Health Command, Army Institute of Public Health , Aberdeen Proving Ground , MD , USA.
authors.forename: Emily
authors.initials: E
authors.lastname: May Lent
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D053834:Explosive Agents / Q000633:toxicity*; D015726:Giant Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D009574:Nitro Compounds / Q000633:toxicity*; D013087:Spermatids / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014230:Triazoles / Q000633:toxicity*
chemical_list: C505897:3-nitro-1,2,4-triazol-5-one; D053834:Explosive Agents; D009574:Nitro Compounds; D014230:Triazoles
keywords: 932-64-9; BALB/c; IMX 101; degeneration; insensitive munitions; mice; testicular effects