Neuromuscular anomalies following oral exposure to 3-nitro-1,2,4-triazol-5-one (NTO) in a one-generation study with Japanese quail (Coturnix japonica)

Abstract

Substances used as explosives in munitions by the military often result in environmental releases through manufacturing, testing, training, and combat activities. The toxicity of 3-nitro-1,2,4-triazol-5-one (nitrotriazolone or NTO) was evaluated following oral exposure in Japanese quail (Coturnix japonica) to determine if environmental releases result in unacceptable risks to avian populations. In an acute test at the limit dose (2000 mg/kg), one female was ataxic, exhibited tremors, and showed signs of neurological toxicity approximately 24 h after dosing. In a subsequent one-generation study, parental generation (F0) birds were exposed orally to 1000, 500, 100, or 20mg/kg-day NTO suspended in corn oil. After 5 consecutive days of dosing, 2-week-old birds receiving 1000 mg/kg-day displayed ataxia, convulsions, backward arching of the neck (opisthotonos), and alternated between prostrate inactivity and ataxic wing activity. Birds in the 500 mg/kg-day group exhibited neuromuscular anomalies after 17 days exposure. Ultimately, all of the 1000 mg/kg-day birds and all but one of the 500 mg/kg-day birds met euthanasia criteria and were humanely euthanized prior to behavioral and reproductive evaluation. As such, first-generation (F1) birds were exposed to 100 or 20 mg/kg-day NTO. Mild neuromuscular anomalies occurred in 10% of F1 birds from the 100 mg/kg-day group, but not in birds from 20 mg/kg-day or controls in either generation. Vacuolization of cerebellum and/or the brainstem was observed on histopathologic examination in a dose-dependent manner. Therefore, brain vacuoles and neuromuscular anomalies were identified as critical endpoints in this study. A mean Benchmark Dose (BMD) for brain vacuoles of 62 mg/kg-day was derived for male and female F0-generation quail, which corresponded to a Benchmark Dose Low (BMDL) of 35 mg/kg-day.

Bacteria Make a Living Breathing the Nitroheterocyclic Insensitive Munitions Compound 3-Nitro-1,2,4-triazol-5-one (NTO)

“…Due to its high solubility (16,642 mg L –1 ) and low p K a (3.76), NTO can dissolve in water quickly upon entering the soil and potentially cause the acidification of the soil solution, affecting the aquatic biota and mobilizing metals . Additionally, NTO was reported to cause toxic effects to several organisms, such as testicular toxicity in male rats, , neuromuscular anomalies in Japanese quail, and abnormal swimming behavior in zebrafish embryos . Therefore, strategies for removing NTO in nontarget environments such as soils, groundwater, and wastewater should be developed.…”

Designing bacterial consortia for the complete biodegradation of insensitive munitions compounds in waste streams

“…Environmental contamination by IMCs can occur via the dissolution of undetonated ordnance in soil or via industrial wastewater discharge (Felt et al, 2013; Hadnagy et al, 2018; Shen et al, 2013; Taylor et al, 2015). IMCs are toxic and potentially mutagenic to many organisms (Crouse et al, 2015; Dodard et al, 2013; Jackovitz et al, 2018; Lent et al, 2020; Liang et al, 2013; Madeira et al, 2018). Therefore, it is imperative to develop treatment strategies for IMC‐related contamination.…”