Chronic Pyraclostrobin Exposure-Induced Developmental Toxicity and ABC Transporter-Associated Metabolism Disorders...

This study evaluated the sublethal effects of pyraclostrobin (PY) (0.750-12.0 μg/L) and its underlying toxic mechanisms following 28 days of embryonic exposure. PY at ≥3.00 μg/L caused developmental toxicity, characterized by increased larval weight, reduced body length, and hepatic and renal impairment. Different PY concentrations similarly altered glucose, pyruvate, total cholesterol, triglyceride, and free fatty acid levels and the transcription of glycolipid metabolism-related genes. Whole-larvae metabolomics further showed that PY simultaneously disrupted ABC transporters, amino acid biosynthesis, and arginine and proline metabolism pathways. Moreover, strobilurins PY, azoxystrobin, and trifloxystrobin induced Abcb4 and Abcb5 transcription during zebrafish embryo-larvae development. Molecular docking revealed that strobilurins formed hydrophobic interactions with conserved Phe793 and Phe1043 residues in zebrafish ABCB5, whereas no conserved binding interactions were observed with ABCB4, suggesting substrate specificity between strobilurins and ABCB5. This study provides potential molecular targets of PY toxicity and highlights the need to assess its chronic ecological risks.