TOXICOKINETICS OF MERCURIC-CHLORIDE AND METHYLMERCURIC CHLORIDE IN MICE
TOXICOKINETICS OF MERCURIC-CHLORIDE AND METHYLMERCURIC CHLORIDE IN MICE
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DOI：
10.1080/15287399209531659
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发表时间：
1992-09-01
期刊：
影响因子：
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通讯作者：
NIELSEN, JB
中科院分区：
文献类型：
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作者：
NIELSEN, JB
未来人类对无机汞的接触可能会导致少数人因职业原因接触高浓度的无机汞，而更多的人则因牙科填充物或含有无机汞的食品而接触低浓度或极低浓度的无机汞；人类对甲基汞的接触量相对较低，并且取决于海洋食物的摄入量。理想情况下，风险评估基于对外部和内部剂量、器官水平及其与中毒症状之间关系的详细了解。然而，关于这些毒代动力学参数的人类数据主要来自个人或较小群体意外短时间暴露于相对较高汞水平的情况，但总体身体负担未知。因此，与接触低含量汞相关的风险评估在很大程度上取决于动物实验的数据。以前对汞化合物的毒代动力学的研究几乎完全采用肠胃外施用相对高剂量的可溶性汞盐。然而，人类接触主要是肺部或口腔，且剂量较低。本研究验证了研究小鼠口服氯化汞和氯化甲基汞毒代动力学的实验模型。使用该模型的主要发现与先前的知识进行了讨论。无机汞在小鼠体内的毒代动力学取决于剂量大小、给药途径和性别，而所用的小鼠品系则不太重要。在两种不同剂量水平下，单次口服剂量的 HgCl2 的“真实吸收”经计算约为 20%。早期的研究没有考虑实验期间吸收汞的可能排泄和肠道重吸收，报告称肠道吸收率为 7-10%。口服 HgCl2 后观察到的排泄率高于腹膜内给药后，很可能是由于全身输送和保留汞的处置差异所致。甲基汞给药后，汞排泄在 2 周内遵循一级动力学，与给药途径、菌株或性别无关。然而，在较长的实验期间，相对屠体保留的增加（排泄速率较慢）导致消除偏离一级动力学。男性和女性之间的甲基汞毒代动力学在排泄率、器官沉积和血液水平方面存在广泛差异。尽管对汞化合物毒代动力学的了解不断增加，但与人体暴露相关的风险评估的实验基础仍有待改进，并简要讨论了进一步实验研究的建议。
Future human exposure to inorganic mercury will probably lead to a few individuals occupationally exposed to high levels and much larger populations exposed to low or very low levels from dental fillings or from food items containing inorganic mercury; human exposure to methylmercury will be relatively low and depending on intake of marine food. Ideally, risk assessment is based on detailed knowledge of relations between external and internal dose, organ levels, and their relation to toxic symptoms. However, human data on these toxicokinetic parameters originate mainly from individuals or smaller populations accidentally exposed for shorter periods to relatively high mercury levels, but with unknown total body burden. Thus, assessment of risk associated with exposure to low levels of mercury will largely depend on data from animal experiments. Previous investigations of the toxicokinetics of mercuric compounds almost exclusively employed parenteral administration of relatively high doses of soluble mercuric salts. However, human exposure is primarily pulmonary or oral and at low doses. The present study validates an experimental model for investigating the toxicokinetics of orally administered mercuric chloride and methylmercuric chloride in mice. Major findings using this model are discussed in relation to previous knowledge.The toxicokinetics of inorganic mercury in mice depend on dose size, administration route, and sex, whereas the mouse strain used is less important. The "true absorption" of a single oral dose of HgCl2 was calculated to be about 20% at two different dose levels. Earlier studies that did not take into account the possible excretion of absorbed mercury and intestinal reabsorption during the experimental period report 7-10% intestinal uptake. The higher excretion rates observed after oral than after intraperitoneal administration of HgCl2 are most likely due to differences in disposition of systemically delivered and retained mercury.After methylmercury administration, mercury excretion followed first-order kinetics for 2 wk, independently of administration route, strain, or sex. However, during longer experimental periods, the increasing relative carcass retention (slower rate of excretion) caused the elimination to deviate from first-order kinetics. Extensive differences in the toxicokinetics of methylmercury with respect to excretion rates, organ deposition, and blood levels were observed between males and females.Despite increasing knowledge on the toxicokinetics of mercuric compounds, the experimental basis for a risk assessment in relation to human exposure could still be improved, and suggestions for further experimental studies are briefly discussed.