硝酸钕28 d经口毒性试验ICR小鼠组织脏器中钕含量及其分布研究

Neodymium content and distribution in ICR mice of a 28-day oral toxicity test for neodymium nitrate

目的用电感耦合等离子体质谱法(ICP-MS)对28 d经口染毒试验ICR小鼠全血和脏器中钕含量进行测定。方法全血和脏器样品经硝酸微波消解、ICP-MS测定,用外标法定量,评价稀土钕元素在小鼠全血和脏器中的含量。结果钕元素的检出限为0.0018μg/L,回收率为97.2%~111.0%,相对标准偏差为1.63%~7.93%,线性相关系数为0.9993,该方法各项指标均符合相关检测要求;硝酸钕连续给药28 d后,心钕含量、肝钕含量和肾钕含量雌性小鼠从12 mg/kg·bw开始明显上升(F值分别为2289.00、37.09和903.50,P<0.05),雄性小鼠从7 mg/kg·bw开始明显上升(F值分别为895.40、38.51和465.30,P<0.05);肺和脾的钕含量雌性小鼠从24 mg/kg·bw开始明显上升(F值分别为3702.00、94.66,P<0.05),雄性小鼠从14 mg/kg·bw开始明显上升(F值分别为4988.00、104.00,P<0.05);脑钕含量雄性小鼠从27 mg/kg·bw开始,明显上升(F值为3.48,P<0.05);睾丸钕含量雄性小鼠从14 mg/kg·bw开始,明显上升(F值为8.28,P<0.05)。血钕含量、脑钕含量、心钕含量、肺钕含量、肝钕含量、脾钕含量、肾钕含量和给药剂量有统计学意义上的相关性[雌性小鼠r值分别为0.85、0.94、0.81、0.97、0.97、0.99、0.93,雄性小鼠r值分别为0.95、0.97、0.81、0.91、0.96、0.97、0.95和0.98(睾丸钕含量),P<0.05]。结论所建立的检测方法准确灵敏,硝酸钕经口摄入可在小鼠体内经血液分布于全身各脏器,其中分布最多的是心脏、肝和肾,其次是肺、脾和睾丸,脑中钕含量较低。不同脏器钕含量与给药剂量有显著的相关性。

Objective To determine the content of neodymium in whole blood and organs of ICR mice after 28 days of oral administration using Inductively Coupled Plasma Mass Spectrometry(ICP-MS).Methods Whole blood and organ samples were digested by nitric acid and microwave,and the content of neodymium was measured by ICP-MS with external standard method for quantification,to evaluate the content of rare earth element neodymium in the whole blood and organs of mice.Results The detection limit of neodymium element was 0.0018μg/L,the recovery rate was between 97.2%and 111.0%,the relative standard deviation was between 1.63%and 7.93%,and the linear correlation coefficient was 0.9993.All indicators of this method met the relevant detection requirements.After continuous administration of neodymium nitrate for 28 days,the contents of neodymium in the heart,liver,and kidney of female mice began to rise significantly from a dosage of 12 mg/kg body weight(bw)(F values were 2289.00,37.09,and 903.50,respectively,P<0.05),and in male mice from 7 mg/kg·bw(F values were 895.40,38.51,and 465.30,respectively,P<0.05);the contents of neodymium in the lung and spleen of female mice began to rise significantly from a dosage of 24 mg/kg·bw(F values were 3702.00 and 94.66,respectively,P<0.05),and in male mice from 14 mg/kg·bw(F values were 4988.00 and 104.00,respectively,P<0.05);the content of neodymium in the brain of male mice began to rise significantly from a dosage of 27 mg/kg·bw(F value was 3.48,P<0.05);the content of neodymium in the testes of male mice began to rise significantly from a dosage of 14 mg/kg·bw(F value was 8.28,P<0.05).There was a statistically significant correlation between the contents of neodymium in the blood,brain,heart,lung,liver,spleen,kidney,and the administered dose(correlation coefficients r for female mice were 0.85,0.94,0.81,0.97,0.97,0.99,0.93,respectively,and for male mice were 0.95,0.97,0.81,0.91,0.96,0.97,0.95,and 0.98(for testicular neodymium content),respectively,P<0.05).Conclusion The established detection method is accurate and sensitive.Neodymium nitrate administered orally can be distributed throughout the body via the bloodstream after intake in mice,with the highest distribution in the heart,liver,and kidney,followed by the lung,spleen,and testes,and lower content in the brain.There is a significant correlation between the content of neodymium in different organs and the administered dose.