Biosciences, University of Exeter, EX4 4PS Exeter, United Kingdom;
Fera Science Ltd., Sand Hutton, YO41 1LZ York, United Kingdom.
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13033-13038. doi: 10.1073/pnas.1804934115. Epub 2018 Dec 3.
Mass mortalities of honey bees occurred in France in the 1990s coincident with the introduction of two agricultural insecticides, imidacloprid and fipronil. Imidacloprid, a neonicotinoid, was widely blamed, but the differential potency of imidacloprid and fipronil has been unclear because of uncertainty over their capacity to bioaccumulate during sustained exposure to trace dietary residues and, thereby, cause time-reinforced toxicity (TRT). We experimentally quantified the toxicity of fipronil and imidacloprid to honey bees and incorporated the observed mortality rates into a demographic simulation of a honey bee colony in an environmentally realistic scenario. Additionally, we evaluated two bioassays from new international guidance for agrochemical regulation, which aim to detect TRT. Finally, we used analytical chemistry (GC-MS) to test for bioaccumulation of fipronil. We found in demographic simulations that only fipronil produced mass mortality in honey bees. In the bioassays, only fipronil caused TRT. GC-MS analysis revealed that virtually all of the fipronil ingested by a honey bee in a single meal was present 6 d later, which suggests that bioaccumulation is the basis of TRT in sustained dietary exposures. We therefore postulate that fipronil, not imidacloprid, caused the mass mortalities of honey bees in France during the 1990s because it is lethal to honey bees in even trace doses due to its capacity to bioaccumulate and generate TRT. Our results provide evidence that recently proposed laboratory bioassays can discriminate harmful bioaccumulative substances and, thereby, address evident shortcomings in a regulatory system that had formerly approved fipronil for agricultural use.
20 世纪 90 年代，法国发生了大规模的蜜蜂死亡事件，当时正值两种农业杀虫剂——吡虫啉和氟虫腈被引入。吡虫啉是一种新烟碱类杀虫剂，因此受到广泛指责，但由于其在持续摄入痕量膳食残留时的生物累积能力存在不确定性，因此吡虫啉和氟虫腈的效力差异并不清楚，而这会导致时间强化毒性（TRT）。我们通过实验量化了氟虫腈和吡虫啉对蜜蜂的毒性，并将观察到的死亡率纳入了一个在环境现实情况下的蜜蜂群体的人口模拟中。此外，我们评估了新的国际农药法规指南中的两项生物测定法，旨在检测 TRT。最后，我们使用分析化学（GC-MS）来测试氟虫腈的生物累积情况。我们在人口模拟中发现，只有氟虫腈会导致蜜蜂大量死亡。在生物测定中，只有氟虫腈会导致 TRT。GC-MS 分析显示，蜜蜂在单次进食中摄入的几乎所有氟虫腈在 6 天后都存在，这表明生物累积是持续膳食暴露中 TRT 的基础。因此，我们假设在 20 世纪 90 年代，法国的蜜蜂大量死亡是由氟虫腈而非吡虫啉引起的，因为由于其生物累积能力和产生 TRT 的能力，即使痕量剂量也会对蜜蜂致命。我们的研究结果表明，最近提出的实验室生物测定法可以区分有害的生物累积物质，从而解决了先前批准氟虫腈用于农业用途的监管系统的明显缺陷。
