Hamazaki S, Okada S, Ebina Y, Midorikawa O
Toxicol Appl Pharmacol. 1985 Feb;77(2):267-74. doi: 10.1016/0041-008x(85)90326-6.
Nitrilotriacetate (NTA), an effective metal-chelating agent, has been used as a substitute for polyphosphates in household laundry detergents. Nephrotoxicity and renal tumorigenicity have been reported in experimental animals that received high doses of NTA po for 4 weeks to 2 years. Since NTA exists in water as a variety of NTA-metal complexes, it was important to investigate the biological effects of NTA in a complexed form. In this study, acute and subchronic toxicity of a ferric iron chelate of NTA (Fe-NTA) was investigated in rats. When Fe-NTA was given ip, acute tubular necrosis and renal failure occurred following a single injection of 15 mg iron/kg. Repeated injections of sublethal doses produced degeneration and necrosis of the proximal tubular epithelium and was associated with polyuria, glucosuria, aminoaciduria, and azotemia. After 9 days of treatment, regeneration of the tubular epithelium with atypical cells was observed. Except for a parenchymal iron deposit, no marked changes were observed in other organs. None of these effects were observed in animals given noncomplexed NTA. In conclusion, the toxicity observed following high doses of NTA given po may be the result of an absorbed metal-NTA chelate.
次氮基三乙酸（NTA）是一种有效的金属螯合剂，已被用作家用洗衣粉中多磷酸盐的替代品。在接受高剂量NTA经口给药4周至2年的实验动物中，已报告有肾毒性和肾致瘤性。由于NTA在水中以多种NTA-金属络合物的形式存在，因此研究络合形式的NTA的生物学效应很重要。在本研究中，对大鼠进行了NTA的铁螯合物（Fe-NTA）的急性和亚慢性毒性研究。当腹腔注射Fe-NTA时，单次注射15mg铁/kg后会发生急性肾小管坏死和肾衰竭。重复注射亚致死剂量会导致近端肾小管上皮细胞变性和坏死，并伴有多尿、糖尿、氨基酸尿和氮质血症。治疗9天后，观察到肾小管上皮细胞再生并伴有非典型细胞。除实质铁沉积外，其他器官未观察到明显变化。在给予非络合NTA的动物中未观察到这些效应。总之，经口给予高剂量NTA后观察到的毒性可能是吸收的金属-NTA螯合物的结果。
