Acute and 90-Day Repeated-Dose Oral Toxicity of Urtica dioica L. Leaf Extract Granules in Rodents
Urtica dioica L. leaves are traditionally used in Indonesia for gout-related complaints, and granules formulated from their ethanolic leaf extract have shown xanthine oxidase inhibitory and uric acid-lowering activity; the safety of the finished formulation, however, remains uncharacterised. This study evaluated acute and repeated-dose oral toxicity under Indonesian National Agency of Drug and Food Control (BPOM) Regulation No. 10 of 2022. Female Swiss Webster mice received a single dose of 5, 50, 500, or 5000 mg/kg granules, and Sprague-Dawley rats of both sexes (five per sex per group) received 77.5, 155, or 310 mg/kg/day for 13 weeks (90 days), with satellite groups observed through a 30-day recovery period. No mortality occurred at 5000 mg/kg, giving an LD50 above that limit; clinical signs, body weight, and rectal temperature showed no dose-related change. After repeated dosing, erythrocyte indices, blood urea nitrogen, and creatinine were unchanged in both sexes. Leukocyte count rose in high-dose females (p < 0.05) but was not observed in the high-dose recovery group, and liver weight differed among female groups without a dose-response pattern. Weight gain at the highest dose differed from control in both sexes but in opposite directions. Control values outside the strain reference range and baseline body-weight imbalance preclude establishing a no-observed-adverse-effect level.