Investigating the interaction between melamine and cyanuric acid using a Physiologically‐Based Toxicokinetic model in rainbow trout
Investigating the interaction between melamine and cyanuric acid using a Physiologically‐Based Toxicokinetic model in rainbow trout
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DOI：
10.1016/j.taap.2019.03.021
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发表时间：
2019-03
影响因子：
3.8
通讯作者：
C. Tebby;C. Brochot;J. Dorne;R. Beaudouin
中科院分区：
文献类型：
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作者：
C. Tebby;C. Brochot;J. Dorne;R. Beaudouin
继2007年和2008年分别爆发饲料和食品中掺入三聚氰胺和氰尿酸混合物和三聚氰胺后，特别是在虹鳟鱼等敏感物种中，对混合物的动力学和毒理动力学进行了研究。在类似的实验条件下，报告了不良反应（肾脏中三聚氰胺-氰尿酸盐晶体形成）的组织浓度和强度。在这里，最近的虹鳟鱼PBTK模型已被应用于模拟两个单一的化合物在组织中的残留水平的基础上的动力学。将单一化合物的两种PBTK模型合并，并添加了三聚氰胺-氰尿酸混合物的晶体形成模型，以在晶体在尿液或肾组织中形成的假设下预测晶体形成的强度。三聚氰胺和三聚氰酸的动力学建模提供了一个更好的理解和预测的晶体形成的强度的情况下，顺序曝光不同的强度或co-exposure.This研究表明，第一次，鱼PBTK模型如何可以发挥关键作用的理解和预测的toxicoketics和toxicodynamics的混合物。该研究还说明了即使化合物不作为混合物一起给药，也可能发生不良反应。
Following outbreaks of feed and food adulterations with a melamine and cyanuric acid mixture in 2007 and melamine in 2008 respectively, the kinetics and toxicodynamics of the mixture have been investigated particularly in sensitive species such as the rainbow trout. Tissue concentrations and intensity of the adverse effect, melamine-cyanurate crystal formation in kidney, were reported in similar experimental conditions. Here, a recent PBTK model for rainbow trout has been applied to model the kinetics of both single compounds based on residue levels in tissues. Both PBTK models for the single compounds were combined and a model of crystal formation for the mixture melamine-cyanuric acid was also added to predict the intensity of crystal formation under the assumptions that crystals formed either in urine or in kidney tissue. Modelling the kinetics of melamine and cyanuric acid provided a better understanding and prediction of intensity of crystal formation in case of sequential exposures with varying intensity or co-exposure.This study demonstrates, for the first time, how fish PBTK models can play a key role in the understanding and prediction of toxicokinetics and toxicodynamics of mixtures. This study also illustrates how adverse effects may potentially occur even when the compounds are not administered together as a mixture.