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题名: 一种适用于标准水生动物急性毒性试验的简化 TKTD模型
作者: 李兆利1
学位类别: 博士后
答辩日期: 2017-11
授予单位: 中国科学院大学
授予地点: 北京
导师: 李建中
关键词: 急性毒性,TKTD模型,MCMC方法,致死速率 Kk ; acute toxicity, TKTD model, MCMC method, killing rate Kk
其他题名: A reduced TKTD model for standard acute toxicity testsof aquatic animals
学位专业: 生物学
中文摘要: 在常规的水生生物急性毒性检测和研究中,最常使用的毒性指标是半数致死 浓度 LC50。然而,该指标严重依赖试验周期,难以科学地比较不同物种之间的毒 性差异。并且,LC50仅为统计学、描述性指标,缺乏生物学涵义。而基于动态存 活模型的致死速率 Killing rate(Kk)不存在上述缺陷,可以作为科学的急性毒性 评价指标。 针对已有的 General Unified Threshold Model of Survival(GUTS)模型的不 足之处,本研究构建了简化的毒物代谢-毒物效应动力学(TKTD)存活模型,采 用 Markov Chain Monte Carlo(MCMC)方法作为最优化算法,用于评价参数 Kk 的可信程度。初步的研究结果表明,MCMC法拟合获得的致死速率 Kk能够可靠 地、稳健地表征急性毒性强度。并且,利用全部试验数据获得的模型参数还有: 主导速率常数 Kd可反映毒性物质的理化性质;无效应浓度 NEC表征不产生死亡 效应的阈值浓度,因此,研究结论具有更高的科学性。 通过设计不同的模拟试验,探讨了本模型的数据要求。结果表明,与标准的 急性毒性试验程序相比,可以减少试验浓度的数量,并且降低了对致死率试验数 据的要求。适用于 TKTD存活模型的最基本的试验设计如下:(1)试验周期内至 少 4次计数死亡动物数目;(2)每个浓度至少设置 2个平行,至少 20只试验动物; (3)试验期间,至少 2个浓度产生了 3个及以上不同的累计死亡率数据。 与以往的动态模型相比,简化 TKTD存活模型更加简便、易用,适用于常 规急性毒性检测和研究。并且,采用本模型可以进行科学的快速毒性检测。
英文摘要: As an indicator used in acute toxicity testing, median lethal concentration LC50 heavily depends on test duration, and was less mechanistic and biologically relevant. However, killing rate Kk derived from dynamic model is free from these drawbacks, so that it would be a more scientific measurement of acute toxicity. To assess the reliability of Kk, a reduced TKTD model of survival was created and optimized with MCMC method. The preliminary results showed that Kk might be a reliable and robust indicator of acute toxicity. Moreover, this model has two other parameters: dominant rate constant Kd, NEC. Kd may indicate some physicochemical properties of a toxicant, and NEC stands for no effect concentration of lethal effect. Therefore, the results utilized all test data were more reliable and scientific. Different simulated tests were set up to explore data requirements of this model. The results showed less data were required of numbers of concentrations and partial mortalities. The basic experiment design for this method was: (1) at least 4 counts of dead individuals through test duration; (2) at least 2 parallels and 20 animals for each treatment; (3) at least 3 different cumulative mortalities in a minimum of 2 treatments. In a summary, killing rate Kk might be a reliable measurement of acute toxicity, and this reduced TKTD model could be applied in routine acute toxicity studies and in some repaid toxicity testing.
内容类型: 学位论文
URI标识: http://ir.rcees.ac.cn/handle/311016/38656
Appears in Collections:中科院环境生物技术重点实验室_学位论文

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作者单位: 1.中国科学院生态环境研究中心

Recommended Citation:
李兆利. 一种适用于标准水生动物急性毒性试验的简化 TKTD模型[D]. 北京. 中国科学院大学. 2017.
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