Nys Charlotte, Asselman Jana, Hochmuth Jennifer D, Janssen Colin R, Blust Ronny, Smolders Erik, De Schamphelaere Karel A C
Faculty of Bioscience Engineering, GhenToxLab, Ghent University, Ghent, Belgium.
Environ Toxicol Chem. 2015 May;34(5):1091-102. doi: 10.1002/etc.2902. Epub 2015 Apr 7.
To incorporate metal mixture toxicity effects into risk-assessment procedures, more information is needed about combined and interactive effects of metal mixtures during chronic exposure. The authors investigated the toxicity of binary Ni-Zn mixtures in 2 independent full-factorial experiments using standard chronic (21-d) Daphnia magna reproduction toxicity tests. Global statistical analysis (i.e., when considering all investigated mixture treatments simultaneously) showed noninteractive effects according to the concentration addition model and significant synergistic effects according to the independent action model. However, treatment-specific statistical analysis revealed that both occurrence and type of interactive effect were dependent on the effect size at which Ni and Zn were combined in the mixture. Only noninteractive or weakly antagonistic effects occurred in mixture treatments in which each of the individual metals produced only weak adverse effects on its own (i.e., ≤20% reduction of reproductive performance). On the other side of the spectrum, synergistic mixture effects occurred in all mixture treatments where both metals already caused a > 20% (for independent action) and a > 40% (for concentration addition) effect on reproduction on their own. Because low effect sizes are the most relevant in most regulatory frameworks, the authors' data suggest that the concentration addition and independent action mixture toxicity models can both serve as conservative models for predicting effects of Ni-Zn mixtures. The present study highlights the importance of investigating metal mixture toxicity at low effect sizes and warns against extrapolating conclusions about metal mixture interactions from high to low effect sizes.
为了将金属混合物的毒性效应纳入风险评估程序，需要更多关于金属混合物在慢性暴露期间的联合效应和交互效应的信息。作者在2个独立的全因子实验中，使用标准的慢性（21天）大型溞繁殖毒性试验，研究了二元镍 - 锌混合物的毒性。全局统计分析（即同时考虑所有研究的混合物处理）显示，根据浓度相加模型为非交互效应，根据独立作用模型为显著的协同效应。然而，特定处理的统计分析表明，交互效应的发生和类型取决于混合物中镍和锌组合时的效应大小。在单个金属自身仅产生微弱不利影响（即生殖性能降低≤20%）的混合物处理中，仅出现非交互或弱拮抗效应。在光谱的另一端，在两种金属自身对繁殖均已造成>20%（对于独立作用）和>40%（对于浓度相加）效应的所有混合物处理中，均出现了协同混合物效应。由于在大多数监管框架中，低效应大小最为相关，作者的数据表明，浓度相加和独立作用混合物毒性模型均可作为预测镍 - 锌混合物效应的保守模型。本研究强调了在低效应大小下研究金属混合物毒性的重要性，并警告不要将关于金属混合物相互作用的结论从高效应大小外推至低效应大小。
