Department of Food Quality & Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel.
Kimron Veterinary Institute, Department of Toxicology, Bet Dagan, 50250, Israel.
Chemosphere. 2021 Mar;266:128974. doi: 10.1016/j.chemosphere.2020.128974. Epub 2020 Nov 13.
Honeybees are exposed to a wide range of pesticides for long periods via contaminated water, pollen and nectar. Some of those pesticides might constitute health hazards in a time- and dose-dependent manner. Time-dependent toxicity profiles for many applied pesticides are lacking, despite the fact that such profiles are crucial for toxicological evaluations. Therefore, we sought to determine the time-dependent toxicities of pesticides/pesticide metabolites frequently found in Israeli beehives, namely, amitraz metabolites, N'-(2,4-dimethylphenyl)-N-methylformamidine (DMPF) and N-(2,4-dimethylphenyl)-formamide (DMF), coumaphos, imidacloprid, thiacloprid, acetamiprid and dimethoate (toxic reference). By applying accepted methodological approaches such as the modified Haber's rule (product of concentration and exposure duration leads to a constant effect) and comparisons between cumulative doses at different time points, we determined the time-dependent toxicities of these pesticides. We also studied the mixture toxicities of frequently occurring pesticide combinations and estimated their potential contributions to the overall toxicities of neonicotinoids. Thiacloprid was the only pesticide that complied with Haber's rule. DMPF, dimethoate and imidacloprid exhibited time-diminished -toxicities. In contrast, DMF and acetamiprid exhibited time-reinforced toxicities. Neither the binary mixtures nor the tertiary mixtures of DMF, DMPF and coumaphos at 10 times their environmentally relevant concentrations potentiated the neonicotinoids' toxicities. DMPF and imidacloprid were found to present the greatest hazard to honeybees, based on their 50% lethal cumulative dose and 50% lethal time. Amitraz's instability, its low detection frequency and high toxicity profile of its metabolite, DMPF, lead us to the conclusion that DMPF constitutes the actual toxic entity responsible for amitraz's toxic effect.
蜜蜂长期通过受污染的水、花粉和花蜜暴露于各种农药中。其中一些农药可能会以时间和剂量依赖的方式构成健康危害。尽管此类时间依赖性毒性特征对于毒理学评估至关重要，但许多应用农药的时间依赖性毒性特征却缺乏。因此，我们试图确定以色列蜂箱中经常发现的农药/农药代谢物的时间依赖性毒性，即咪鲜胺代谢物、N'-(2,4-二甲基苯基)-N-甲基甲脒（DMPF）和 N-(2,4-二甲基苯基）-甲酰胺（DMF）、氯菊酯、吡虫啉、噻虫啉、噻虫胺和乐果（毒性参考物）。通过应用公认的方法学方法，如修正的哈伯规则（浓度与暴露时间的乘积导致恒定的效应）和不同时间点的累积剂量之间的比较，我们确定了这些农药的时间依赖性毒性。我们还研究了经常出现的农药组合的混合物毒性，并估计了它们对新烟碱类化合物整体毒性的潜在贡献。噻虫啉是唯一符合哈伯规则的农药。DMPF、乐果和吡虫啉表现出时间减弱的毒性。相比之下，DMF 和噻虫胺表现出时间增强的毒性。在环境相关浓度的 10 倍下，DMF、DMPF 和氯菊酯的二元混合物和三元混合物均未增强新烟碱类化合物的毒性。根据 50%致死累积剂量和 50%致死时间，我们发现 DMPF 和吡虫啉对蜜蜂的危害最大。咪鲜胺的不稳定性、其代谢物 DMPF 的低检测频率和高毒性特征使我们得出结论，DMPF 是导致咪鲜胺毒性的实际有毒实体。
