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贝叶斯群体生理药代动力学(PBPK)建模和马尔可夫链蒙特卡罗模拟在保护海洋哺乳动物中农药动力学研究中的应用:DDT、DDE 和 DDD 在港豚中的研究。

Application of Bayesian population physiologically based pharmacokinetic (PBPK) modeling and Markov chain Monte Carlo simulations to pesticide kinetics studies in protected marine mammals: DDT, DDE, and DDD in harbor porpoises.

机构信息

Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.

出版信息

Environ Sci Technol. 2013 May 7;47(9):4365-74. doi: 10.1021/es400386a. Epub 2013 Apr 18.

Abstract

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and variability, parameter estimation methods are required for the development of reliable PBPK models. The present study is the first to develop PBPK models for the lifetime bioaccumulation of p,p'-DDT, p,p'-DDE, and p,p'-DDD in harbor porpoises. In addition, this study is also the first to apply the Bayesian approach executed with Markov chain Monte Carlo simulations using two data sets of harbor porpoises from the Black and North Seas. Parameters from the literature were used as priors for the first "model update" using the Black Sea data set, the resulting posterior parameters were then used as priors for the second "model update" using the North Sea data set. As such, PBPK models with parameters specific for harbor porpoises could be strengthened with more robust probability distributions. As the science and biomonitoring effort progress in this area, more data sets will become available to further strengthen and update the parameters in the PBPK models for harbor porpoises as a species anywhere in the world. Further, such an approach could very well be extended to other protected marine mammals.

摘要

生理基础药代动力学(PBPK)模型在海洋哺乳动物中是一个挑战,因为缺乏参数信息和暴露实验禁令。为了最小化不确定性和可变性,需要参数估计方法来开发可靠的 PBPK 模型。本研究首次为港湾海豚体内 p,p'-DDT、p,p'-DDE 和 p,p'-DDD 的终生生物累积开发了 PBPK 模型。此外,本研究还首次应用贝叶斯方法,通过马尔可夫链蒙特卡罗模拟,使用来自北海和黑海的两个港湾海豚数据集。使用来自文献中的参数作为第一个“模型更新”的先验,使用黑海数据集,然后使用后验参数作为第二个“模型更新”的先验,使用北海数据集。因此,可以使用更稳健的概率分布来加强针对港湾海豚的 PBPK 模型的参数。随着该领域的科学和生物监测工作的进展,将有更多的数据集可用于进一步加强和更新世界各地港湾海豚 PBPK 模型的参数。此外,这种方法可以很好地扩展到其他受保护的海洋哺乳动物。

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