Department of Biochemistry, University of Cambridge, The Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Ecotoxicology. 2012 Jul;21(5):1436-47. doi: 10.1007/s10646-012-0897-0. Epub 2012 Apr 4.
A major challenge in ecotoxicology is to understand the effects of multiple toxicants on organisms. Here we assess the effects on survival, weight change, cocoon production and metabolism caused by exposure to two similarly acting (imidacloprid/thiacloprid) and two dissimilarly acting (chlorpyrifos/Nickel) chemicals on the earthworm Lumbricus rubellus. We assessed the standard models of concentration addition (CA) and independent action (IA), in conjunction with a metabolomics based approach to elucidate mechanisms of effect. For imidacloprid and thiacloprid the reproductive effects indicated probable additivity. Although this suggests joint effects through a similar mechanism, metabolite changes for each pesticide actually indicated distinct effects. Further, earthworms exposed to a 0.5 toxic unit equitoxic mixture demonstrated metabolic effects intermediate between those for each pesticide, indicating a non-interactive, independent joint effect. For higher effect level mixtures (1 and 1.5 toxic units), metabolite changes associated with thiacloprid exposure began to dominate. The metabolomic effects of the two dissimilarly acting chemicals were distinct, confirming separate modes of action and both proved more toxic than anticipated from previous studies. In the mixtures, phenotypic effects were in accordance with IA estimates, while metabolite changes were dominated by Ni effects, even though chlorpyrifos contributed most to reproductive toxicity. This could be attributed to the greater systematic effect of Ni when compared to the more specifically acting chlorpyrifos.
在生态毒理学中，一个主要的挑战是理解多种毒物对生物的影响。在这里，我们评估了两种具有类似作用（吡虫啉/噻虫啉）和两种作用不同（毒死蜱/镍）的化学物质暴露对蚯蚓 Lumbricus rubellus 的生存、体重变化、茧产量和代谢的影响。我们评估了浓度加和（CA）和独立作用（IA）的标准模型，结合基于代谢组学的方法来阐明作用机制。对于吡虫啉和噻虫啉，生殖效应表明可能存在加和性。虽然这表明通过类似的机制产生联合效应，但每种农药的代谢物变化实际上表明存在不同的效应。此外，暴露于 0.5 毒性单位等毒性混合物的蚯蚓表现出介于每种农药之间的代谢效应，表明存在非交互、独立的联合效应。对于更高效应水平的混合物（1 和 1.5 毒性单位），与噻虫啉暴露相关的代谢物变化开始占主导地位。两种作用不同的化学物质的代谢组学效应截然不同，证实了不同的作用模式，而且都比以前的研究预期的更具毒性。在混合物中，表型效应与 IA 估计相符，而代谢物变化则主要受 Ni 影响，尽管毒死蜱对生殖毒性的贡献最大。这可能归因于 Ni 的系统作用大于更具特异性的毒死蜱。
