ACUTE FIPRONIL SULFONE TOXICITY INDUCES MULTI-ORGAN HISTOPATHOLOGY IN MALE MICE: A COMPREHENSIVE HISTOMORPHOMETRIC ANALYSIS

Abstract Fipronil sulfone is the predominant metabolite of the insecticide fipronil, produced via cytochrome P450 oxidation. It exhibits greater persistence and higher toxicity than its parent compound, yet its histopathological effects remain unexplored. To evaluate histopathological changes induced by acute fipronil sulfone exposure in male mice. Sixteen adult male mice were divided into control (DMSO) and treated (100 mg/kg fipronil sulfone, intraperitoneal) groups (n=8). Liver, kidney, brain, testis, and seminal vesicles were processed for H&E, PAS, and Trichrome staining. Histomorphometric analysis was performed using ImageJ software. Fipronil sulfone caused significant testicular damage including reduced tubular diameter (168.32±7.54 vs. 212.45±8. 67 µm), epithelial height (58.67±2.93 vs. 78.34±3.21 µm), tunica albuginea thickness (28.43±1.89 vs. 42.67±2.31 µm), and increased interstitial space (7.96±0.61 vs. 4.82±0.34 µm) and tubular lumen (72.56±3.78 vs. 45.23±2.45 µm). Seminal vesicles showed metaplasia and increased epithelial height (27.89±1.67 vs. 18.34±1.23 µm). Renal damage included reduced corpuscle (3187±142 vs. 4234±156 µm²) and glomerular area (1978±87 vs. 2845±98 µm²), increased Bowman's space (567±31 vs. 312±24 µm²), and PCT brush border loss. Hepatic alterations showed increased pericentral degenerated hepatocytes (12.7±1.3 vs. 3.4±0.5 per field). Hippocampal neurodegeneration increased significantly (21.6±2.1 vs. 5.2±0.8 degenerated neurons per field). All changes were statistically significant (p<0.05). This first comprehensive study demonstrates that acute fipronil sulfone exposure induces significant multi-organ histopathological damage in mice, highlighting the need for risk assessment of pesticide metabolites.