Dose-Response Evaluation of Blumea balsamifera Leaf Ethanol Extract in Acute and Subchronic Toxicity Models in Mice for Sustainable Application

Abstract

Blumea balsamifera is widely used in traditional medicine, yet its safety profile remains inadequately characterized. This study aimed to assess the dose-dependent toxicity of Blumea balsamifera leaf ethanol extract (BBEE) through acute (14 days) and subchronic (90 days) oral exposure in Swiss albino mice at doses ranging from 100 to 5000 mg/kg, including recovery groups to evaluate reversibility. Toxicological endpoints included body weight, food intake, organ weights, hematological indices, serum biochemistry, and urinalysis. High BBEE doses significantly reduced body weight gain (5.3 ± 1.6% vs. 40.5 ± 2.2%, p = 0.007) and food intake (R² = 0.9966), and increased relative liver (r = 0.991) and kidney (r = 0.985) weights (p < 0.01). Notable elevations were observed in RBC (8.55 ± 0.13 × 10⁶/mm³, p = 0.012), creatinine (r = 0.846, p = 0.014), BUN (r = 0.926, p = 0.009), and urinary pH (r = 0.973, p = 0.007). However, all alterations were dose-dependent and fully normalized in satellite groups (p > 0.05). Overall, BBEE induced reversible physiological and biochemical changes at high doses, while lower doses were well tolerated. These findings support the safe use of BBEE at moderate levels and its potential for further development as a sustainable natural product.