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从加性到统计学显著偏差:在评估混合物毒性时,它们意味着什么?

Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures?

机构信息

Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands.

Institute of Environmental Sciences (CML), Leiden University, 2300 RA Leiden, The Netherlands.

出版信息

Ecotoxicol Environ Saf. 2015 Dec;122:37-44. doi: 10.1016/j.ecoenv.2015.07.012. Epub 2015 Jul 17.

DOI:10.1016/j.ecoenv.2015.07.012
PMID:26188643
Abstract

There is increasing attention from scientists and policy makers to the joint effects of multiple metals on organisms when present in a mixture. Using root elongation of lettuce (Lactuca sativa L.) as a toxicity endpoint, the combined effects of binary mixtures of Cu, Cd, and Ni were studied. The statistical MixTox model was used to search deviations from the reference models i.e. concentration addition (CA) and independent action (IA). The deviations were subsequently interpreted as 'interactions'. A comprehensive experiment was designed to test the reproducibility of the 'interactions'. The results showed that the toxicity of binary metal mixtures was equally well predicted by both reference models. We found statistically significant 'interactions' in four of the five total datasets. However, the patterns of 'interactions' were found to be inconsistent or even contradictory across the different independent experiments. It is recommended that a statistically significant 'interaction', must be treated with care and is not necessarily biologically relevant. Searching a statistically significant interaction can be the starting point for further measurements and modeling to advance the understanding of underlying mechanisms and non-additive interactions occurring inside the organisms.

摘要

越来越多的科学家和政策制定者关注到,当多种金属混合存在于环境中时,它们会对生物体产生联合效应。本研究以生菜根伸长作为毒性终点,研究了铜、镉和镍二元混合物的联合效应。采用统计混合毒性模型(MixTox model)来寻找偏离参考模型(即浓度加和模型(CA)和独立作用模型(IA))的情况,将偏差解释为“相互作用”。设计了一项全面的实验来检验“相互作用”的重现性。结果表明,两种参考模型都能很好地预测二元金属混合物的毒性。在五个总数据集的四个中,我们发现了统计学上显著的“相互作用”。然而,在不同的独立实验中,“相互作用”的模式被发现不一致甚至相互矛盾。因此建议,对于统计学上显著的“相互作用”,必须谨慎处理,并且不一定具有生物学相关性。寻找统计学上显著的相互作用,可以作为进一步测量和建模的起点,以推进对生物体内部潜在机制和非加性相互作用的理解。

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