Nishie K, Fiddler W, Pensabene J W
J Toxicol Environ Health. 1984;13(4-6):595-608. doi: 10.1080/15287398409530524.
The effects of N-nitrosothiazolidine (NNT) and N-nitrosomorpholine (NNM) on different biological parameters were investigated and compared. The oral LD50 value of NNT (1950 +/- 85 mg/kg) showed that it was about 6 times less toxic than NNM (LD50 = 320 mg/kg, po; Druckrey et al., 1967). Lethal and near-lethal doses (greater than or equal to 1500 mg/kg, po) of NNT caused central nervous system depression (reduced spontaneous motor activity, loss of righting and pain reflexes, without loss of consciousness), stereotypical behavior such as, purposeless chewing jaw movements lasting more than one hour, muscular rigidity, and in some rats, rare and brief clonic convulsions, 3 to 24 h after dosing. These neurotoxic signs, as a whole, were reminiscent of opioid intoxication. Rats that died after NNT-treatment had kidney necrosis in the distal tubules, but all survivors had normal kidneys. NNT (500 and 1000 mg/kg, sc) had no effect on the relative liver weights, but it inhibited liver mitosis at 24, 48, and 72 h after treatment. NNM (100 mg/kg, sc) decreased the relative liver weights on 3 posttreatment days; it inhibited liver mitosis after 24 h and enhanced it after 48 h in male rats. Both NNT and NNM increased the relative adrenal weights, but only NNM enhanced adrenocortical mitosis. In general, NNT had no effect on serum enzymes (SGOT, SGPT, LDH, HBDH), but it increased blood urea nitrogen (BUN) and serum creatinine 24 h after administration. Pretreatment of rats with 3 doses of NNT (150 mg/kg X d, po) increased the pentobarbital-induced sleep (PST) by 26% (not significant), while 3 doses of NNM (50 mg/kg X d, po) increased PST by 188%. In addition, NNM caused a severe centrilobular liver necrosis and glycogen depletion, associated with a marked rise in serum enzymes (SGOT, SGPT, LDH, HBDH) and fall in serum glucose. Compared with NNM, NNT, which was found in fried bacon (Kimoto et al., 1982; Gray et al., 1982), seemed to be a relatively nontoxic nitrosamine.
研究并比较了N - 亚硝基噻唑烷（NNT）和N - 亚硝基吗啉（NNM）对不同生物学参数的影响。NNT的经口半数致死量（LD50）值为（1950±85mg/kg），表明其毒性约为NNM（LD50 = 320mg/kg，经口；Druckrey等人，1967）的六分之一。NNT的致死和接近致死剂量（大于或等于1500mg/kg，经口）给药后3至24小时会导致中枢神经系统抑制（自发运动活动减少、翻正反射和疼痛反射消失，但意识未丧失）、刻板行为，如持续超过一小时的无目的咀嚼颌部运动、肌肉僵硬，部分大鼠还会出现罕见且短暂的阵挛性惊厥。总体而言，这些神经毒性体征让人联想到阿片类药物中毒。NNT处理后死亡的大鼠远端肾小管出现肾坏死，但所有存活大鼠的肾脏正常。NNT（500和1000mg/kg，皮下注射）对肝脏相对重量无影响，但在处理后24、48和72小时抑制肝脏有丝分裂。NNM（100mg/kg，皮下注射）在处理后的3天降低肝脏相对重量；在雄性大鼠中，它在24小时后抑制肝脏有丝分裂，48小时后增强有丝分裂。NNT和NNM均增加肾上腺相对重量，但只有NNM增强肾上腺皮质有丝分裂。一般来说，NNT对血清酶（谷草转氨酶、谷丙转氨酶、乳酸脱氢酶、羟丁酸脱氢酶）无影响，但给药后24小时会增加血尿素氮（BUN）和血清肌酐。用3剂NNT（150mg/kg×d，经口）预处理大鼠使戊巴比妥诱导的睡眠时间（PST）增加26%（无显著性差异），而3剂NNM（50mg/kg×d，经口）使PST增加188%。此外，NNM导致严重的小叶中心性肝坏死和糖原耗竭，伴有血清酶（谷草转氨酶、谷丙转氨酶、乳酸脱氢酶、羟丁酸脱氢酶）显著升高和血糖下降。与NNM相比，在煎培根中发现的NNT（Kimoto等人，1982；Gray等人，1982）似乎是一种相对无毒的亚硝胺。
