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.

• 932-64-9
• BALB/c
• degeneration
• IMX 101
• insensitive munitions
• mice
• testicular effects

Acknowledgements

The authors thank the WRAIR technicians and animal husbandry staff, especially Tesafaye Mekonnen. We would like to thank Karl P. Kroeck for performing the analytical chemistry.

Declaration of interest

This work was supported by funding from the Strategic Environmental Research and Development Program (SERDP Project ER-2223). The authors declare no competing interests. Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true view of the Department of the Army or the Department of Defense.