Testicular effects of 3-nitro-1,2,4-triazol-5-one (NTO) in mice when exposed orally

作     者：Mullins, Anna B. Despain, Kenneth E. Wallace, Shannon M. Honnold, Cary L. Lent, Emily May 

作者机构：Walter Reed Army Inst Res Vet Serv Program Naval Med Res Ctr 503 Robert Grant Ave Silver Spring MD 20910 USA US Army Publ Hlth Command Army Inst Publ Hlth Aberdeen Proving Ground MD USA 

出 版 物：《TOXICOLOGY MECHANISMS AND METHODS》 (毒理学机理与方法)

年 卷 期：2016年第26卷第2期

页      面：97-103页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Strategic Environmental Research and Development Program (SERDP) [ER-2223] 

主　　题：932-64-9 BALB c degeneration IMX 101 insensitive munitions mice testicular effects 

摘      要：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 1000mg/kg-day NTO for 1, 3, 7 or 14 d were evaluated. The earliest NTO-induced testicular changes occurred in the 1000mg/kg-day group at day 7 and the 500mg/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 500mg/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, 1000mg/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.