唑类杀菌剂混合物对近头状尖孢藻的毒性相互作用评估
Assessment of Toxicity Interactions of Azole Fungicides Mixtures on Raphidocelis subcapitata
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摘要: 唑类杀菌剂广泛存在水环境中，对水生生物产生有害影响，且其混合物的毒性相互作用未知。为探讨复合的唑类杀菌剂对非靶标生物绿藻的毒性相互作用，以苯醚甲环唑、戊菌唑、叶菌唑、四氟醚唑、粉唑醇、麦穗宁、氟菌唑、土菌灵和噁霉灵共9种唑类杀菌剂作为混合物组分，运用直接均分射线法设计了173条二元混合物射线，采用微板毒性分析法系统测定二元混合物对近头状尖孢藻(Raphidocelis subcapitata)的生长抑制毒性。以半数效应浓度(EC50)的负对数(pEC50)作为判断毒性大小的指标，173组二元唑类杀菌剂混合物的pEC50范围为3.053～6.415，含有叶菌唑和麦穗宁的混合物的毒性最大，最高毒性的pEC50分别为6.415和6.140。通过浓度加和、独立作用模型及其等效线图定性分析混合物毒性相互作用，采用模型偏差比、毒性单位法、相加指数法、混合毒性指数和组合指数定量评估混合物毒性相互作用。结果表明，混合物毒性相互作用通过毒性单位法、混合物毒性指数和组合指数的评价结果更为一致。由苯醚甲环唑、戊菌唑和氟菌唑设计的二元混合产生协同作用的频次更高，分别为46.9%、46.1%和61.1%。由粉唑醇、麦穗宁和叶菌唑设计的二元混合会降低混合物毒性，呈现为加和作用和拮抗作用。杀菌剂混合物毒性相互作用规律总体表现为低浓度的以协同、加和作用为主，高浓度以加和作用、拮抗作用为主。在环境浓度下，混合物相互作用主要以加和作用为主。Abstract: The widespread presence of azole fungicides in aquatic environments has raised concerns about their potential harmful effects on the growth of aquatic organisms. However, the toxic interactions that may occur when these fungicides are combined remain largely unexplored. To investigate these interactions on non-target organisms, specifically green algae, we selected nine azole fungicides, namely difenoconazole, penconazole metconazole, tetraconazole, flutriafol, fuberidazole, triflumizole, terrazole, and hymexazol, to create binary mixtures. A total of 173 binary mixtures were created using a direct equipartition ray design. The microplate toxicity analysis method was used to systematically measure the growth inhibition toxicity of these mixtures on Raphidocelis subcapitata. Toxicity was assessed using the negative logarithm of the median effective concentration (pEC50) as an indicator. The pEC50 values of 173 binary triazole fungicide mixtures ranged from 3.053 to 6.415. Mixtures containing metcona-zole and fuberidazole showed the highest toxicity, with maximum pEC50 values of 6.415 and 6.140, respectively. Toxicity interactions were qualitatively analyzed using concentration addition, independent action, and isobologram approaches. Quantitative assessments were performed using model deviation ratio, toxic unit, additivity index, mixture toxicity index, and combination index methods. The results showed that the binary mixtures designed with difenoconazole, penconazole, and triflumizole exhibited a higher frequency of synergistic effects, with occurrences of 46.9%, 46.1%, and 61.1%, respectively. In contrast, mixtures designed with flutriafol, fuberidazole, and metcona-zole generally exhibited reduced toxicity, showing additive and antagonistic effects. The toxic unit，mixture toxicity index, and combination index methods produced more consistent evaluations of these interactions. The mixtures predominantly showed synergistic and additive effects at low concentrations, while additive and antagonistic effects were more prevalent at high concentrations. The interactions of the mixtures were mainly additive at environmentally relevant concentrations.
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Key words:
- azole fungicides /
- Raphidocelis subcapitata /
- combined toxicity /
- predictive model
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