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.

中文翻译：

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3-硝基-1,2,4-三唑-5-酮（NTO）在大鼠中的慢性口服毒性。

为了评估长期暴露于3-硝基-1,2,4-三唑-5-酮（硝基三唑酮，NTO）的影响，雌雄大鼠在饮用水中的浓度分别为0、36， 110、360、1100和3600 mg / L一年。无论男女，NTO均未影响体重，体重增加或食物消耗。在6个月或一年的采样中，在临床化学和血液学参数方面未观察到与治疗相关的影响。在中期和最终采样中，与对照组相比，3600 mg / L组的雄性和雌性产生的尿液体积更小，更暗，更浓缩并且含有更多的胆红素。总精子和活动精子数不受NTO治疗的影响。对照组和NTO治疗组的男女性别绝对和相对器官重量均无差异。自发的与年龄有关的肿瘤发生在对照组和NTO组，其发生率与已公布的历史对照组一致。在所测试的剂量下，NTO通常对女性无毒。如先前的研究所示，男性的毒性仅限于睾丸毒性。长期暴露在较低剂量下不会导致睾丸毒性，并且仅在高剂量组中观察到的毒性不如先前研究中在较短剂量下观察到的严重，这表明差异可能与研究设计对动力学的影响有关。确定NTO对男性的慢性影响的基准剂量（BMD）为1604 mg / L（76 mg / kg-day）和基准剂量下限（BMDL10）为921 mg / L（44 mg / kg-day）大鼠。在所测试的剂量下，NTO通常对女性无毒。如先前的研究所示，男性的毒性仅限于睾丸毒性。长期暴露在较低剂量下不会导致睾丸毒性，并且仅在高剂量组中观察到的毒性不如先前研究中在较短剂量下观察到的严重，这表明差异可能与研究设计对动力学的影响有关。确定NTO对男性的慢性影响的基准剂量（BMD）为1604 mg / L（76 mg / kg-day）和基准剂量下限（BMDL10）为921 mg / L（44 mg / kg-day）大鼠。在所测试的剂量下，NTO通常对女性无毒。如先前的研究所示，男性的毒性仅限于睾丸毒性。长期暴露在较低剂量下不会导致睾丸毒性，并且仅在高剂量组中观察到的毒性不如先前研究中在较短剂量下观察到的严重，这表明差异可能与研究设计对动力学的影响有关。确定NTO对男性的慢性影响的基准剂量（BMD）为1604 mg / L（76 mg / kg-day）和基准剂量下限（BMDL10）为921 mg / L（44 mg / kg-day）大鼠。长期暴露在较低剂量下不会导致睾丸毒性，并且仅在高剂量组中观察到的毒性不如先前研究中在较短剂量下观察到的严重，这表明差异可能与研究设计对动力学的影响有关。确定NTO对男性的慢性影响的基准剂量（BMD）为1604 mg / L（76 mg / kg-day）和基准剂量下限（BMDL10）为921 mg / L（44 mg / kg-day）大鼠。长期暴露在较低剂量下不会导致睾丸毒性，并且仅在高剂量组中观察到的毒性不如先前研究中在较短剂量下观察到的严重，这表明差异可能与研究设计对动力学的影响有关。确定NTO对男性的慢性影响的基准剂量（BMD）为1604 mg / L（76 mg / kg-day）和基准剂量下限（BMDL10）为921 mg / L（44 mg / kg-day）大鼠。