Endocrine Disruption Induced by Environmental Exposure to the Acaricide Cyflumetofen and Its Main Metabolite

Cyflumetofen (CYF) and its main metabolite, trifluoromethyl benzoic acid (B-1), both of which contain a trifluoromethyl group, are increasingly used in agriculture due to their high stability and efficacy. Structurally, these molecules share several physicochemical features with per- and polyfluoroalkyl substances (PFASs), including endocrine disruption and reproductive toxicity. This study aims to evaluate the reproductive toxicity effects of CYF and its metabolites using adult zebrafish as a model organism. The results indicate that exposure to CYF and B-1 at environmentally relevant concentrations for 21 days causes hormonal disruption and abnormal gonadal development in fish; moreover, as the concentrations increase, CYF and B-1 significantly impair the reproductive capacity of zebrafish and lead to developmental abnormalities in their offspring. Based on the ratio of E2/T and the alteration of key genes in the HPG axis, such as cyp17a2 and cyp11c1, it is hypothesized that CYF and B-1 disrupt hormonal homeostasis via the HPG axis. Notably, male fish were more susceptible when exposed to CYF or B-1, exhibiting sex-specific differences. RNA-seq analysis revealed that CYF/B-1 promotes Ca²⁺ release from the zebrafish brain and induces steroid hormone dysregulation based on the HPG axis via genes such as hsd17a and gnrh. In summary, this study provides key insights into the reproductive toxicity of CYF and its major metabolite, highlighting their risks to the environment and human health.