Variation in the biological half-life of methylmercury in humans: Methods, measurements and meaning.
Variation in the biological half-life of methylmercury in humans: Methods, measurements and meaning.
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人类甲基汞生物半衰期的变化：方法、测量和意义。
DOI：
10.1016/j.bbagen.2019.02.003
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Caito,SamuelW
中科院分区：
文献类型：
--
作者：
Rand,MatthewD;Caito,SamuelW
背景了解甲基汞（MeHg）的毒性需要完全了解其在人体内的基本毒代动力学和毒代动力学特征。甲基汞的生物半衰期（t1/2）是一种动力学特性，它直接影响汞的体内负荷，汞的体内负荷是由于反复接触所致，例如食用鱼类和海产品时可能发生的情况。甲基汞在人体内的半衰期约为50天，相当于0.014天-1的消除率（kel）。然而，许多研究报告的半衰期值范围很广（t1/2 < 30 to >120天），这表明甲基汞消除的生物过程存在显著差异。这种变化是一个相当大的不确定性的来源，在推导出一个有意义的参考剂量适用于所有个人在population.Scope的甲基汞首先，我们总结了基本面的甲基汞toxicokeretics，强调生物半衰期在甲基汞剂量学中发挥的核心作用。接下来，我们提出了如何进行动力学分析的重要考虑。我们提供了一个例子，说明甲基汞半衰期的变化如何直接影响身体负担，在某些情况下，可能导致甲基汞水平超过美国环保署的参考剂量。然后，我们调查现有的研究，报告甲基汞半衰期determinations.Major conclusionsRecent进展的方法，确定甲基汞动力学的人作出了个性化的评估，甲基汞消除率更准确，更容易获得。将减少围绕甲基汞暴露的剩余毒代动力学不确定性，并将更好地为风险评估过程提供信息。
BackgroundUnderstanding methylmercury (MeHg) toxicity requires a complete understanding of its fundamental toxicokinetic and toxicodynamic characteristics in the human body. The biological half-life (t1/2) of MeHg is a kinetic property that directly influences the body burden of Hg that results from repeated exposures such as can occur with fish and seafood consumption. The t1/2of MeHg in humans is approximately 50 days, equivalent to an elimination rate (kel) of 0.014 day−1. However, numerous studies report a wide range of half-life values (t1/2< 30 to >120 days), demonstrating that significant variation in the biological process of MeHg elimination exists. This variation is a source of considerable uncertainty in deriving a meaningful reference dose for MeHg applicable to all individuals in a population.Scope of reviewFirst, we summarize fundamentals of MeHg toxicokinetics, emphasizing the central role that biological half-life plays in MeHg dosimetry. We next present important considerations for how kinetic analyses are performed. We provide an example of how MeHg half-life variation directly influences the body burden and, in certain contexts, can result in MeHg levels exceeding the US EPA Reference Dose. We then survey existing studies that report MeHg half-life determinations in people.Major conclusionsRecent advances in methods of determining MeHg kinetics in people have made individualized assessment of MeHg elimination rates more accurate and readily obtainable.General significanceCharacterization of MeHg half-life, particularly in vulnerable individuals, such as pregnant women and children, will diminish the remaining toxicokinetic uncertainty surrounding MeHg exposures and will better inform the risk assessment process.