镍的未观察到有害作用剂量研究及其在生物相容性评价中应用初探

Study of No Observed Adverse Effect Level of Nickel and Its Preliminary Evaluation Biocompatibility

摘要: 为获得静脉途径镍暴露的NOAEL以便科学高效地评价含镍医疗器械的生物相容性，该研究通过两个阶段，第一阶段4.9、3.7、2.5 mg/（kg·d），第二阶段1.2及0.25 mg/（kg·d），共5个剂量组以连续14 d静脉给予SD大鼠含镍离子（Ni²⁺）溶液的方式，研究镍对大鼠的亚慢性全身毒性作用，结果显示当给予镍离子剂量为0.25 mg/（kg·d）时，大鼠未表现出亚慢性全身毒性反应，并经镍钛合金材料验证该结论。由此以100倍安全因子推算，对于体重60 kg成人，镍离子的TTC为150 μg/d。

Abstract: The purpose of this study was to investigate the NOAEL of the nickel ion and provide with basic data for the biological evaluation of those medical devices containing nickel. Five groups SD rats were repeatedly exposed during 14 d respectively to nickel at first stage doses of 4.9, 3.7, 2.5 mg/(kg.d), and the second stage doses of 1.2, 0.25 mg/(kg.d) by the intravenous route. The results showed that the NOAEL of nickel ion is 0.25 mg/(kg.d) for SD rats, and the result was verified by subchronic systemic toxicity test of nickel alloy. The threshold of toxicological concern (TTC) of nickel is 150 μg/d (based on application of 100-fold uncertainty factor and a body weight of 60 kg)deduced by these data.