Death Dilemma and Organism Recovery in Ecotoxicology
Death Dilemma and Organism Recovery in Ecotoxicology
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DOI：
10.1021/acs.est.5b03079
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发表时间：
2015-08-18
影响因子：
11.4
通讯作者：
Escher, Beate I.
中科院分区：
文献类型：
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作者：
Ashauer, Roman;O'Connor, Isabel;Escher, Beate I.
为什么有些人在接触化学物质后能存活，而有些人却会死亡？要么容忍阈值在一个种群的个体中是分布的，超过容忍阈值就会导致一定的死亡，要么所有个体都有相同的容忍阈值，超过容忍阈值就会随机死亡。先前发表的通用统一生存阈值模型（GUTS）在这两种假设之间建立了数学关系。根据该模型，随机死亡会产生比个体容忍更快的系统补偿和损伤修复机制。因此，我们面临一个循环结论困境，因为关于死亡机制的推断与损害恢复的速度内在地联系在一起。我们提供的经验证据表明，随机死亡模型始终比个体耐受模型推断更快的毒物动力学恢复。生存数据可以用更慢的伤害恢复和更宽的个体容忍度分布来解释，或者更快的伤害恢复与更窄的容忍度分布相匹配。毒理学模型参数在化学空间中表现出有意义的模式，这就是为什么我们建议毒理学模型参数作为体外到体内毒性外推的新表型锚点。GUTS似乎是传统生存曲线分析和剂量反应模型的一个有希望的改进。
Why do some individuals survive after exposure to chemicals while others die? Either, the tolerance threshold is distributed among the individuals in a population, and its exceedance leads to certain death, or all individuals share the same threshold above which death occurs stochastically. The previously published General Unified Threshold model of Survival (GUTS) established a mathematical relationship between the two assumptions. According to this model stochastic death would result in systematically faster compensation and damage repair mechanisms than individual tolerance. Thus, we face a circular conclusion dilemma because inference about the death mechanism is inherently linked to the speed of damage recovery. We provide empirical evidence that the stochastic death model consistently infers much faster toxicodynamic recovery than the individual tolerance model. Survival data can be explained by either, slower damage recovery and a wider individual tolerance distribution, or faster damage recovery paired with a narrow tolerance distribution. The toxicodynamic model parameters exhibited meaningful patterns in chemical space, which is why we suggest toxicodynamic model parameters as novel phenotypic anchors for in vitro to in vivo toxicity extrapolation. GUTS appears to be a promising refinement of traditional survival curve analysis and dose response models.