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Use of (Q)SAR genotoxicity predictions and fuzzy multicriteria decision-making for priority ranking of ethoxyquin transformation products
Environment International ( IF 10.3 ) Pub Date : 2021-10-01 , DOI: 10.1016/j.envint.2021.106875
J D Rasinger 1 , F Frenzel 2 , A Braeuning 2 , A Bernhard 1 , R Ørnsrud 1 , S Merel 3 , M H G Berntssen 1
Affiliation  

Ethoxyquin (EQ; 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) has been used as an antioxidant in feed for pets and food-producing animals, including farmed fish such as Atlantic salmon. In Europe, the authorization for use of EQ as a feed additive was suspended, due to knowledge gaps concerning the presence and toxicity of EQ transformation products (TPs). Recent analytical studies focusing on the detection of EQ TPs in farmed Atlantic salmon feed and fillets reported the detection of a total of 27 EQ TPs, comprising both known and previously not described EQ TPs. We devised and applied an in silico workflow to rank these EQ TPs according to their genotoxic potential and their occurrence data in Atlantic salmon feed and fillet. Ames genotoxicity predictions were obtained applying a suite of five (quantitative) structure–activity relationship ((Q)SAR) tools, namely VEGA, TEST, LAZAR, Derek Nexus and Sarah Nexus. (Q)SAR Ames genotoxicity predictions were aggregated using fuzzy analytic hierarchy process (fAHP) multicriteria decision-making (MCDM). A priority ranking of EQ TPs was performed based on combining both fAHP ranked (Q)SAR predictions and analytical occurrence data. The applied workflow prioritized four newly identified EQ TPs for further investigation of genotoxicity. The fAHP-based prioritization strategy described here, can easily be applied to other toxicity endpoints and groups of chemicals for priority ranking of compounds of most concern for subsequent experimental and mechanistic toxicology analyses.



中文翻译:

使用 (Q)SAR 遗传毒性预测和模糊多准则决策对乙氧喹转化产物进行优先排序

Ethoxyquin (EQ; 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) 已被用作宠物和食用动物饲料中的抗氧化剂,包括大西洋鲑鱼等养殖鱼类。在欧洲,由于对 EQ 转化产品 (TPs) 的存在和毒性的认识不足,暂停了使用 EQ 作为饲料添加剂的授权。最近关注在养殖大西洋鲑鱼饲料和鱼片中检测 EQ TP 的分析研究报告共检测到 27 个 EQ TP,包括已知和以前未描述的 EQ TP。我们设计并应用了计算机根据它们的遗传毒性潜力和它们在大西洋鲑鱼饲料和鱼片中的出现数据对这些 EQ TP 进行排名的工作流程。应用一套五种(定量)构效关系 ((Q)SAR) 工具,即 VEGA、TEST、LAZAR、Derek Nexus 和 Sarah Nexus,获得了 Ames 基因毒性预测。(Q) SAR Ames 遗传毒性预测是使用模糊层次分析法 (fAHP) 多标准决策 (MCDM) 进行汇总的。基于结合 fAHP 排序 (Q) SAR 预测和分析发生数据对 EQ TP 进行优先排序。应用的工作流程优先考虑了四个新确定的 EQ TP,以进一步研究遗传毒性。此处描述的基于 fAHP 的优先级策略,

更新日期:2021-10-02
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