Department of Biology/Toxicology, Ashland University, Ashland, OH, 44805, USA,
Arch Environ Contam Toxicol. 2014 Feb;66(2):248-58. doi: 10.1007/s00244-013-9981-6. Epub 2013 Dec 25.
Mixture toxicity for each of four ethyl α-halogenated acetates with each of three α-halogenated acetonitriles (xANs) was assessed. Inhibition of bioluminescence in Vibrio fischeri was measured after 15, 30, and 45 min of exposure. Concentration-response curves were developed for each chemical at each exposure duration and used to develop predicted concentration-response curves for the dose-addition and independence models of combined effect. Concentration-response curves for each mixture and each exposure duration were then evaluated against the predicted curves using three metrics per model: (1) EC50-based additivity quotient (AQ) or independence quotient (IQ) values; (2) mean AQ (mAQ) or mean IQ (mIQ) values, which were calculated by averaging the EC25, EC50, and EC75 AQ or IQ values; and (3) deviation values from additivity (DV-A) or independence (DV-I). Mixture toxicity for ethyl iodoacetate was dose-additive with each of the xANs at all exposure durations and was also often consistent with independence. The same was true for mixture toxicity of ethyl bromoacetate with each xAN. However, for the two more slowly reactive chemicals, ethyl chloroacetate (ECAC) and ethyl fluoroacetate (EFAC), mixture toxicity with each xAN only became consistent with dose-addition on increasing exposure duration. Consistency with independence for both ECAC and EFAC with the xANs was essentially limited to the EC50-IQ metric, thereby showing the utility of calculating the mean quotient (mAQ, mIQ) and deviation value (DV-A, DV-I) metrics. On review of these findings with those from the first two studies in the series, the results suggest that instances in which mixture toxicity was not consistent with dose-addition relate (1) to differences in the capability of the chemicals to form strong H-bonds with water; and (2) to differences in relative reactivity and time-dependent toxicity levels of the chemicals.
评估了四种乙基α-卤代乙酸酯与三种α-卤代乙腈（xANs）中的每一种的混合物毒性。在暴露 15、30 和 45 分钟后，测量了发光菌 Vibrio fischeri 的生物发光抑制。为每种化学物质在每种暴露时间下开发了浓度-反应曲线，并用于为剂量相加和独立效应的组合效应模型开发预测的浓度-反应曲线。然后，使用每个模型的三个指标，根据三个指标评估每种混合物和每种暴露时间的浓度-反应曲线与预测曲线的一致性：（1）基于 EC50 的加性商（AQ）或独立性商（IQ）值；（2）平均 AQ（mAQ）或平均 IQ（mIQ）值，通过平均 EC25、EC50 和 EC75 AQ 或 IQ 值来计算；（3）偏离加性的偏差值（DV-A）或独立性（DV-I）。在所有暴露时间下，乙基碘代乙酸与每种 xAN 的混合物毒性均呈剂量相加，且通常也与独立性一致。乙基溴代乙酸与每种 xAN 的混合物毒性也是如此。然而，对于两种反应较慢的化学物质，乙基氯代乙酸（ECAC）和乙基氟代乙酸（EFAC），只有在增加暴露时间的情况下，与每种 xAN 的混合物毒性才与剂量相加一致。ECAC 和 EFAC 与 xAN 之间的独立性一致性基本上仅限于 EC50-IQ 指标，从而显示出计算平均商（mAQ、mIQ）和偏差值（DV-A、DV-I）指标的有用性。在与该系列前两项研究的结果进行回顾时，这些发现表明混合物毒性与剂量相加不一致的情况与以下两个因素有关：（1）化学物质与水形成氢键的能力的差异；（2）化学物质的相对反应性和时间依赖性毒性水平的差异。
