Subacute oral toxicity of flutriafol in mice: Behavioral,biochemical,and histological alterations

Abstract

Human exposure to triazole fungicides such as flutriafol (FFL) is raising concerns regarding their potential toxic effects. FFL has been reported to induce oxidative stress and systemic toxicity, yet its subacute effects remain incompletely characterized. This study investigated the subacute oral toxicity of FFL in adult male mice, with a particular focus on behavioral, biochemical, hematological, and histological alterations. Behavioral assessment and median lethal dose (LD₅₀) determination were performed initially. Mice were then administered FFL by oral gavage at doses of 25, 50, 75, or 100 mg/kg body weight for 15 consecutive days. Hematological indices and biochemical parameters reflecting hepatic, renal, cardiac, and lipid metabolic function were evaluated. Oxidative stress markers, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and thiobarbituric acid–reactive substances (TBARS), were measured in multiple organs, including the liver, intestine, brain, kidney, testis, lungs, pancreas, and heart. Histological examinations were conducted to assess tissue-level alterations. FFL exposure resulted in dose-dependent behavioral changes, hematological disturbances, and significant alterations in serum biochemical parameters. Antioxidant enzyme activities were reduced, while lipid peroxidation was increased across several organs, indicating enhanced oxidative stress. These findings were supported by histopathological changes consistent with organ injury. In conclusion, subacute oral exposure to FFL induced behavioral and multisystem toxicity in mice, largely mediated by oxidative stress mechanisms. These results highlight potential health risks associated with repeated FFL exposure and underscore the need for further toxicological evaluation.