摘要:
等效线与等效面在化学混合物毒性相互作用评价方面具有综合、直观、有效等特点。但目前等效面尚无有效的绘制方法,主要原因是三元混合物组分浓度配比缺乏有效、直观的试验设计方法。根据三组分混合物等效面的三角形特征,提出了一种新的均分等效面设计(EESD)方法用于三元组分浓度配比试验设计。最终,得到了组分的9个毒性单位(EC50)比,分别是1:1:7、4:1:4、2:2:5、1:4:4、7:1:1、5:2:2、4:4:1、2:5:2、1:7:1。按照惯例还增加一个毒性单位比1:1:1的等毒性浓度比混合物射线。组分两两混合按照直接均分射线法进行毒性单位比1:5、2:4、3:3、4:2、5:1设计15个二元混合物射线。单个组分在浓度轴上的3个ECx点构成了等效面的3个顶点。这28个等效点采用基于三角形的3次插值得到混合物x%效应的观测等效面。基于EESD构建了[BMIM]BF4、灭多威、敌敌畏的混合物对乙酰胆碱酯酶抑制效应为80%、50%、20%的等效面。等效面分析表明,除了1:1:7混合物射线在80%与50%效应时为拮抗作用外,三元混合物体系总体上为加和作用。同时给出了三元混合物EESD方法设计的一般规则。EESD方法可有效用于三元组分的浓度配比优化设计与三维等效面的绘制。
Abstract:
Isobole and equivalent surface were used to investigate interactions among the toxic gradients in chemical mixtures. The lack of effective and intuitive methods to design concentration ratio of the ternary mixtures, causes the failure of drawing the equivalent-surface for toxicity assessment. Derived from ternary compounds equivalent-surface's triangular feature, we described a novel equipartition equivalent-surface design (EESD) method for ternary-component concentration-ratio design. Following the EESD protocol, (A) ternary compounds assay suggested 9 toxic units (EC50) ratios (1:1:7, 4:1:4, 2:2:5, 1:4:4, 7:1:1, 5:2:2, 4:4:1, 2:5:2, 1:7:1), plus equal-toxic concentration ratio 1:1:1. (B) Binary compounds assay suggested 5 mixture rays by the direct equipartition ray design, with each pair of binary compounds ratios of 1:5, 2:4, 3:3, 4:2, and 5:1. (C) Single compound assay suggested 3 ECx points on the concentration axis of the three vertices of the equivalent-surface. (D) These 28 equivalent-effect points were used to construct the observed x%-effect equivalent-surface of the mixture by using the triangle-based cubic interpolation. The EESD assay was tested on ternary mixture of[BMIM]BF4, methomyl and dichlorvos with equivalent-surfaces 80%, 50% and 20% effects on inhibiting acetylcholinesterase, respectively. Our results showed that most of ternary mixture system was additive effects except that the 1:1:7 mixture ray was antagonistic effects at 80% and 50% equivalent-surfaces. Additionally, we presented the guideline of EESD method for ternary mixtures assessment. In conclusion, the EESD method can be used to optimize the concentration ratio of ternary components and to draw the 3D equivalent-surface for mixture toxicity.
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