Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden.
Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden; University of Duisburg-Essen, Forsthausweg 2, 47057 Duisburg, Germany.
Aquat Toxicol. 2022 Jul;248:106175. doi: 10.1016/j.aquatox.2022.106175. Epub 2022 Apr 25.
Risk assessment of chemicals is still primarily focusing on single compound evaluation, even if environmental contamination consists of a mixture of pollutants. The concentration addition (CA) and independent action (IA) models have been developed to predict mixture toxicity. Both models assume no interaction between the components, resulting in an additive mixture effect. In the present study, the embryo toxicity test (OECD TG no. 236) with zebrafish embryos (Danio rerio) was performed to investigate whether the toxicity caused by binary, ternary, and quaternary mixtures of organic (Benzo[a]pyrene, perfluorooctanesulfonate, and 3,3´,4,4´,5-pentachlorobiphenyl 126) and inorganic (arsenate) pollutants can be predicted by CA and IA. The acute toxicity and sub-lethal alterations such as lack of blood circulation were investigated. The models estimated the mixture toxicity well and most of the mixtures were additive. However, the binary mixture of PFOS and PCB126 caused a synergistic effect, with almost a ten-fold difference between the observed and predicted LC-value. For most of the mixtures, the CA model was better in predicting the mixture toxicity than the IA model, which was not expected due to the chemicals' different modes of action. In addition, some of the mixtures caused sub-lethal effects not observed in the single compound toxicity tests. The mixture of PFOS and BaP caused a division of the yolk and imbalance was caused by the combination of PFOS and As and the ternary mixture of PFOS, As, and BaP. Interestingly, PFOS was part of all three mixtures causing the mixture specific sub-lethal effects. In conclusion, the present study shows that CA and IA are mostly resulting in good estimations of the risks that mixtures with few components are posing. However, for a more reliable assessment and a better understanding of mixture toxicity, further investigations are required to study the underlying mechanisms.
化学品的风险评估仍然主要集中在单一化合物的评估上，即使环境污染物是混合物。浓度加和（CA）和独立作用（IA）模型已经被开发出来以预测混合物毒性。这两个模型都假设成分之间没有相互作用，从而导致混合物的加性效应。在本研究中，使用斑马鱼胚胎（Danio rerio）进行胚胎毒性测试（OECD TG no. 236），以研究有机（苯并[a]芘、全氟辛烷磺酸和 3,3´,4,4´,5-五氯联苯 126）和无机（砷酸盐）污染物的二元、三元和四元混合物引起的毒性是否可以通过 CA 和 IA 来预测。研究了急性毒性和亚致死改变，如血液循环缺失。模型很好地估计了混合物毒性，大多数混合物是加性的。然而，PFOS 和 PCB126 的二元混合物表现出协同作用，观察到的 LC 值与预测的 LC 值相差近十倍。对于大多数混合物，CA 模型比 IA 模型更能预测混合物毒性，这与预期的由于化学品的不同作用模式而不同。此外，一些混合物引起了在单一化合物毒性测试中未观察到的亚致死效应。PFOS 和 BaP 的混合物导致卵黄分裂，PFOS 和 As 的组合导致不平衡，PFOS、As 和 BaP 的三元混合物也导致不平衡。有趣的是，PFOS 是引起混合物特异性亚致死效应的所有三种混合物的一部分。总之，本研究表明，CA 和 IA 主要导致对具有少量成分的混合物所构成的风险的良好估计。然而，为了进行更可靠的评估和更好地理解混合物毒性，需要进一步研究潜在机制。
