Expanding the insight of ecological risk on the novel chiral pesticide mefentrifluconazole: Mechanism of enantioselective toxicity to earthworms (Eisenia fetida)

Continued application of new chiral fungicide mefentrifluconazole (MFZ) increases its risk to soil ecosystem. However, the toxicity of MFZ enantiomers to soil fauna and whether stereoselectivity exists remains poorly elucidated. Based on multilevel toxicity endpoints and transcriptomics, we investigated the negative effects of racemic, R-(-)-, and S-(+)-MFZ on Eisenia fetida. After exposure to S-(+) configuration at 4 mg/kg for 28 day, its reactive oxygen species levels were elevated by 15.4% compared to R-(-) configuration, inducing enantiospecific oxidative stress and transcriptional aberrations. The S-(+) isomer induced more severe cell membrane damage and apoptosis than the R-(-) isomer, and notably, the selectivity of apoptosis is probably dominated by the mitochondrial pathway. Mechanistically, differential mitochondrial stress lies in: S-(+) isomer specifically up-regulated mitochondrial cellular component compared to R-(-) isomer and identified more serious mitochondrial fission. Furthermore, S-(+) conformation down-regulated biological processes associated with ATP synthesis and metabolism, with specific inhibition of mitochondrial respiratory electron transport chain complex I and IV activity resulting in more severe electron flow disturbances. These ultimately mediated enantioselective ontogenetic process disorders, which were supported at phenotypic (weight loss), genetic, and protein (reverse modulate TCTP and Sox2 expression) levels. Our findings offer an important reference for elucidating the enantioselective toxicological mechanism of MFZ in soil fauna.