Medinsky M A, Benson J M, Hobbs C H
Environ Res. 1987 Jun;43(1):168-78. doi: 10.1016/s0013-9351(87)80068-3.
Epidemiology studies have indicated increased incidences of respiratory tract and renal cancer in nickel refinery workers. Since the most likely route of exposure to nickel in the workplace is via the respiratory tract, the objectives of the experiments described here were to determine the retention pattern of Ni in the lungs, identify the target organs for Ni absorbed from the respiratory tract, and determine rates for excretion of Ni. Male and female F344 rats were given 17, 190, or 1800 nmoles Ni (as a nickel sulfate solution) in saline, containing trace amounts of 63Ni, by intratracheal instillation. Urine and feces were collected, and rats were necropsied at predetermined times up to 96 hr after instillation. At all times, lungs, trachea, larynx, kidney, and urinary bladder contained the highest concentrations of Ni as determined by liquid scintillation spectrometry. Urine was the major route for excretion of Ni, accounting for 50% of the dose after instillation of 17 or 190 nmoles Ni, and 80% of the dose after instillation of 1800 nmoles Ni. The half-time for urinary excretion of Ni increased from 4.6 hr at the highest dose to 23 hr at the lowest dose used. Fecal excretion accounted for 30% (17- and 190-nmole doses) or 13% (1800 nmoles) of the initial dose. Of the Ni remaining in the body at the end of 96 hr, over 50% was in the lungs. The long-term half-time for clearance of Ni from the lungs ranged from 21 hr at the highest dose to 36 hr at the lowest dose instilled. As the amount of instilled Ni decreased, the fraction of the instilled Ni associated with the long-term clearance component increased (from 24% at the highest dose to 40% at the lowest dose). Results suggest that, over the range of doses studied, both pulmonary clearance of Ni and routes for excretion of Ni were dependent on the instilled dose.
流行病学研究表明，镍精炼厂工人呼吸道和肾癌的发病率有所增加。由于在工作场所接触镍的最可能途径是通过呼吸道，因此本文所述实验的目的是确定镍在肺部的滞留模式，确定从呼吸道吸收的镍的靶器官，并确定镍的排泄率。通过气管内滴注，给雄性和雌性F344大鼠注射17、190或1800纳摩尔镍（以硫酸镍溶液形式，溶于含有微量⁶³Ni的盐水中）。收集尿液和粪便，并在滴注后长达96小时的预定时间对大鼠进行尸检。通过液体闪烁光谱法测定，在所有时间点，肺、气管、喉、肾和膀胱中的镍浓度最高。尿液是镍排泄的主要途径，注射17或190纳摩尔镍后，尿液排泄量占剂量的50%，注射1800纳摩尔镍后，尿液排泄量占剂量的80%。镍的尿排泄半衰期从最高剂量时的4.6小时增加到所用最低剂量时的23小时。粪便排泄占初始剂量的30%（17和190纳摩尔剂量）或13%（1800纳摩尔）。在96小时结束时，体内残留的镍中，超过50%在肺部。镍从肺部清除的长期半衰期范围从最高剂量时的21小时到最低滴注剂量时的36小时。随着滴注镍量的减少，与长期清除成分相关的滴注镍比例增加（从最高剂量时的24%增加到最低剂量时的40%）。结果表明，在所研究的剂量范围内，镍的肺部清除和排泄途径均取决于滴注剂量。
