A comprehensive review of strobilurin fungicide toxicity in aquatic species: Emphasis on mode of action from the zebrafish model

Strobilurins are popular fungicides used in agriculture on a global scale. Due to their widespread use as agrochemicals, they can enter aquatic environments at concentrations that can elicit adverse effects in organisms. This review synthesizes the current state of knowledge regarding the toxic effects of strobilurin fungicides on aquatic species, including algal species, Daphnia magna, and fish species, to determine risk to aquatic organisms and ecosystems. Data show that the toxicities of strobilurins vary widely across aquatic species. Strobilurins bind cytochrome bc1 in mitochondrial complex III in fungi, and as such, research in aquatic species has focused on mitochondria-related endpoints following exposures to strobilurins. In fish, studies into the activities of mitochondrial complexes and the expression of genes involved in the electron transfer chain have been conducted, converging on the theme that mitochondrial complexes and their enzymes are impaired by strobilurins. In general, the order of toxicity of strobilurins for fish species are pyraoxystrobin > pyraclostrobin ≈ trifloxystrobin > picoxystrobin > kresoxim-methyl > fluoxastrobin > azoxystrobin. In addition to mitochondrial toxicity, studies also report genotoxicity, immunotoxicity, cardiotoxicity, neurotoxicity, and endocrine disruption, and each of these events can potentially impact whole organism-level processes such as development, reproduction, and behavior. Screening data from the US Environmental Protection Agency ToxCast database supports the hypothesis that these fungicides may act as endocrine disruptors, and high throughput data suggest estrogen receptor alpha and thyroid hormone receptor beta can be activated by some strobilurins. It is recommended that studies investigate the potential for endocrine disruption by strobilurins more thoroughly in aquatic species. Based on molecular, physiological, and developmental outcomes, a proposed adverse outcome pathway is presented with complex III inhibition in the electron transfer chain as a molecular initiating event. This review comprehensively addresses sub-lethal toxicity mechanisms of strobilurin fungicides, important as the detection of strobilurins in aquatic environments suggests exposure risks in wildlife.