Chronic oral toxicity of 3-nitro-1,2,4-triazol-5-one (NTO) in rats

Abstract To evaluate the effects of chronic exposure to 3-nitro-1,2,4-triazol-5-one (nitrotriazolone, NTO), male and female rats were given ad libitum access to NTO in drinking water at concentrations of 0, 36, 110, 360, 1100, and 3600 mg/L for one year. NTO did not affect body weight, body weight gain, or food consumption in either sex. No treatment-related effects were observed in clinical chemistry and hematology parameters at the 6 month or one year sampling. At both the interim and final sampling, males and females from the 3600 mg/L group produced smaller volumes of urine that was darker, more concentrated, and contained more bilirubin than the controls. Total and motile sperm counts were not affected by NTO treatment. Absolute and relative organ weights did not differ between control and NTO treated groups for either sex. Spontaneous age-related neoplasms occurred in controls and NTO groups at rates consistent with published historic controls. NTO was generally non-toxic in females at the doses tested. Toxicity in males was limited to testicular toxicity as demonstrated in previous studies. Chronic exposure did not result in testicular toxicity at lower doses and the toxicity observed only in the high dose group in this study is less severe than that observed in shorter exposures of previous studies, suggesting differences may be associated with influences of study design on kinetics. A Benchmark Dose (BMD) of 1604 mg/L (76 mg/kg-day) and a Benchmark Dose Lower Bound (BMDL10) of 921 mg/L (44 mg/kg-day) were determined for chronic effects of NTO in male rats.