Dawson Douglas A, Guinn Daphne, Pöch Gerald
Department of Biology/Toxicology, Ashland University, Ashland, OH, USA.
Department of Pharmacology and Toxicology, University of Graz, Graz, Austria.
Toxicol Rep. 2016;3:572-583. doi: 10.1016/j.toxrep.2016.07.003. Epub 2016 Jul 25.
Mixture and time-dependent toxicity (TDT) was assessed for a series of mono-halogenated acetonitrile-containing combinations. Inhibition of bioluminescence in was measured after 15, 30 and 45-min of exposure. Concentration-response (x/y) curves were determined for each chemical alone at each timepoint, and used to develop predicted x/y curves for the dose-addition and independence models of combined effect. The x/y data for each binary mixture was then evaluated against the predicted mixture curves. Two metrics of mixture toxicity were calculated per combined effect model: (1) an EC-based dose-addition (AQ) or independence (IQ) quotient and (2) the mixture/dose-addition (MX/DA) and mixture/independence (MX/I) metrics. For each single chemical and mixture tested, TDT was also calculated. After 45-min of exposure, 25 of 67 mixtures produced curves that were consistent with dose-addition using the MX/DA metric, with the other 42 being less toxic than predicted by MX/DA. Some mixtures had toxicity that was consistent with both dose-addition and independence. In general, those that were less toxic than predicted for dose-addition were also less toxic than predicted for independence. Of the 25 combinations that were consistent with dose-addition, 22 (88%) mixtures contained chemicals for which the individual TDT values were both >80%. In contrast, of the 42 non-dose-additive combinations, only 2 (4.8%) of the mixtures had both chemicals with individual TDT values >80%. The results support previous findings that TDT determinations can be useful for predicting chemical mixture toxicity.
对一系列含单卤代乙腈的组合进行了混合物和时间依赖性毒性（TDT）评估。在暴露15、30和45分钟后测量生物发光抑制情况。在每个时间点分别测定每种化学物质的浓度-反应（x/y）曲线，并用于建立联合效应的剂量相加和独立模型的预测x/y曲线。然后根据预测的混合物曲线评估每个二元混合物的x/y数据。每个联合效应模型计算两个混合物毒性指标：（1）基于EC的剂量相加（AQ）或独立（IQ）商数，以及（2）混合物/剂量相加（MX/DA）和混合物/独立（MX/I）指标。对于测试的每种单一化学物质和混合物，还计算了TDT。暴露45分钟后，67种混合物中有25种产生的曲线与使用MX/DA指标的剂量相加一致，其他42种混合物的毒性低于MX/DA预测值。一些混合物的毒性与剂量相加和独立均一致。一般来说，那些毒性低于剂量相加预测值的混合物，其毒性也低于独立预测值。在与剂量相加一致的25种组合中，22种（88%）混合物所含化学物质的个体TDT值均>80%。相比之下，在42种非剂量相加组合中，只有2种（4.8%）混合物的两种化学物质的个体TDT值>80%。结果支持了之前的研究发现，即TDT测定可用于预测化学混合物毒性。
