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General Unified Threshold Model of Survival - a Toxicokinetic- Toxicodynamic Framework for Ecotoxicology

机译：生存的通用统一阈值模型-生态毒理学的毒代动力学-毒理动力学框架

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摘要

Toxicokinetic-toxicodynamic models (TKTD models) simulate the time-course of processes leading to toxic effects on organisms. Even for an apparently simple endpoint as survival, a large number of very different TKTD approaches exist. These differ in their underlying hypotheses and assumptions, although often the assumptions are not explicitly stated. Thus, our first objective was to illuminate the underlying assumptions (individual tolerance or stochastic death, speed of toxicodynamic damage recovery, threshold distribution) of various existing modeling approaches for survival and show how they relate to each other (e.g., critical body residue, critical target occupation, damage assessment, DEBtox survival, threshold damage). Our second objective was to develop a general unified threshold model for survival (GUTS), from which a large range of existing models can be derived as special cases. Specific assumptions to arrive at these special cases are made and explained. Finally, we illustrate how special cases of GUTS can be fitted to survival data. We envision that GUTS will help increase the application of TKTD models in ecotoxicological research as well as environmental risk assessment of chemicals. It unifies a wide range of previously unrelated approaches, clarifies their underlying assumptions, and facilitates further improvement in the modeling of survival under chemical stress.
机译：毒代动力学-动力学模型（TKTD模型）模拟了导致对生物体产生毒性作用的过程的时程。即使对于一个看似简单的生存终点，也存在大量非常不同的TKTD方法。尽管通常没有明确陈述这些假设，但它们的基本假设和假设有所不同。因此，我们的首要目标是阐明各种现有的生存建模方法的基本假设（个体耐受力或随机死亡，毒物动力学损伤恢复的速度，阈值分布），并展示它们之间的相互关系（例如，关键的身体残留，关键的目标职业，损害评估，DEBtox生存率，阈值损害）。我们的第二个目标是开发一个通用的统一生存阈值模型（GUTS），从中可以导出大量现有模型作为特殊情况。做出并解释了得出这些特殊情况的具体假设。最后，我们说明了如何将GUTS的特殊情况应用于生存数据。我们预想，GUTS将有助于增加TKTD模型在生态毒理学研究和化学品环境风险评估中的应用。它统一了许多以前不相关的方法，阐明了它们的基本假设，并促进了在化学胁迫下生存模型的进一步改进。

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  • 来源
    《Environmental Science & Technology》 |2011年第7期|p.2529-2540|共12页
  • 作者

    Tjalling Jager; Carlo Albert; Thomas G. Preuss; Roman Ashauer;

  • 作者单位

    Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam, The Netherlands;

    Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Diibendorf, Switzerland;

    institute for Environmental Research, RWTH Aachen University, Worringerweg 1, D-52064, Aachen, Germany;

    Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Diibendorf, Switzerland,institute for Environmental Research, RWTH Aachen University, Worringerweg 1, D-52064, Aachen, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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