Insect-Mediated Metabolic Activation of Etofenprox Amplifies Hidden Aquatic Toxicity in Rice Ecosystems

Pyrethroid insecticides, though effective against pests, often exhibit high toxicity to aquatic organisms. A notable exception is etofenprox, which is uniquely approved for rice paddies due to its low aquatic toxicity. However, this study uncovers a hidden ecological risk: etofenprox undergoes metabolic activation in the insect pest Nilaparvata lugens via oxidation mediated by cytochrome P450 CYP425A1. The oxidation converts the etofenprox ether bond into an ester (α-CO, 2-(4-ethoxyphenyl)-2-methylpropyl 3-phenoxybenzoate), a hallmark of potent pyrethroids. This transformation dramatically amplifies aquatic toxicity, with α-CO exhibiting 23-79-fold higher lethality in fish and crabs than the parent compound, reaching levels comparable to those of conventional pyrethroids like cypermethrin. Our findings challenge the traditional structure-toxicity paradigms by uncovering a dynamic "metabolic activation-toxicity amplification" mechanism. Crucially, this bioactivation creates an indirect exposure pathway in integrated rice-fish-crab systems, where predators ingest toxic metabolite-laden pests, escalating ecological risks. This study reveals insect-mediated metabolic conversion as a critical driver of hidden aquatic toxicity. This finding redefines pesticide risk assessment by advocating for mandatory metabolite toxicity evaluation alongside parent compounds. Our results urge a reconsideration of etofenprox's safety in aquatic agroecosystems, with broader implications for pyrethroid design and unforeseen ecological risks.