Oral Toxicity of 3-Nitro-1,2,4-triazol-5-one in Rats

Abstract

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d.

Sequential anaerobic-aerobic biodegradation of emerging insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO)

“…In contrast with TNT, which is well known for its mutagenic potential (Kennel et al, 2000), NTO has been shown to be negative in a variety of assays for genotoxicity and mutagenicity assays (Kirby, 2008; Song, 2008a; Song, 2008b). The subacute and subchronic toxicity of NTO to rats has been evaluated by Crouse et al (2015). Male adult rats receiving a dose of 1000 mg kg -1 body wt d -1 NTO or greater during 14 days exhibited decreased food consumption and body mass.…”

Toxicity of Insensitive Munition (IMX) Formulations and Components

“…NTO had no effect on mortality,f ood consumption, body weight, or neurobehavioralp arameters. Moderate to severe testicular hypoplasia, characterized by interstitial degeneration and loss of spermatogenic epithelium in the seminiferous tubules, was observed in the testes in 86 %a nd 100 %o f males from the 315 and 1000 mg kg À1 -d dose groups, respectively.E pididymal aspermia was also observeda tt hese dose levels [19].T he testiculare ffectsw eret he most sensitive adverse effect and were used to derive aB MDL10 of 40 mg kg À1 -d.…”

“…Results from a1 4-day subacute oral toxicity studyo f NTO in rats showed significantly decreasedt estes weights in the high dose groups (! 500 mg kg À1 -d [19]).…”

“…Because previous studies had consistentlyi dentified the testes and epididymides as potential targets of NTO [19,20],t ests were then conducted to ascertain the possibility that these effectsc ould be manifested throughe ndocrine disruptive mechanisms. NTO was tested in nine endocrine disruptor bioassays.…”

Biotransformation and photolysis of 2,4-dinitroanisole, 3-nitro-1,2,4-triazol-5-one, and nitroguanidine

“…18,20,61,76 In preliminary studies, the acute toxicity, mutagenicity, and genotoxicity of NTO and NQ appear to be less than traditional explosive compounds, but NTO yielded reproductive effects in male rats at high concentrations. 47,51,149 Recent data also suggest that toxicity from NTO and NQ to Ceriodaphnia dubia increases 1000-fold upon photolysis, and only a small fraction of NTO was degraded during the photolysis period examined. 38 NQ photolysate is also toxic to zebrafish embryos.…”