Jonsson F, Sandborgh-Englund G, Johanson G
Department of Occupational Medicine-Toxicology, National Institute for Working Life, Solna, Sweden.
Toxicol Appl Pharmacol. 1999 Mar 1;155(2):161-8. doi: 10.1006/taap.1998.8585.
In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples were collected. In the present study, the experimental observations from eight of these volunteers were subjected to an analysis with the aid of the software NONMEM. A four-compartment model, including two depot compartments to account for retention in lungs and kidneys, respectively, gave the best fit to the data. The fraction of dose excreted from the central compartment directly into urine was found to be positively correlated with the preexposure excretion rate of Hg via urine. The median half time in the respiratory depot compartment was estimated to 1.81 days (range 1.60-1.92). The median half time in the excretion depot was estimated to 63.2 days (range 12.8-98.9). The model was tested by simulating two experiments found in the literature and agreed well with these older data sets. Further simulations indicated that the excretion of Hg via urine would not reach a plateau until several months postexposure for most subjects.
在一项早期研究中,我们让9名健康志愿者在轻度体育锻炼(50瓦)期间,暴露于已知浓度的空气中汞(Hg)蒸气中(中位数399;范围365 - 430微克/立方米)15分钟(桑德伯格 - 英格伦德,G.等人,《毒理学与应用药理学》150,146 - 153,1998年)。收集了呼出气、尿液和血浆样本。在本研究中,借助NONMEM软件对其中8名志愿者的实验观察结果进行了分析。一个四室模型,包括两个储存室,分别用于解释肺部和肾脏中的滞留情况,对数据的拟合效果最佳。发现从中央室直接排泄到尿液中的剂量分数与暴露前通过尿液排泄汞的速率呈正相关。呼吸储存室的中位半衰期估计为1.81天(范围1.60 - 1.92)。排泄储存室的中位半衰期估计为63.2天(范围12.8 - 98.9)。通过模拟文献中发现的两个实验对该模型进行了测试,结果与这些较早的数据集吻合良好。进一步的模拟表明,对于大多数受试者,暴露后几个月内通过尿液排泄的汞才会达到平台期。