In vivo toxicological profiling of Teucrium polium L. fractions: indications of safety via oral and dermal routes

Abstract

Teucrium polium L. is widely consumed as a traditional remedy across the Mediterranean basin and North Africa, yet its safety remains contentious due to published cases of herb-induced liver injury in humans. This study examined the in vivo tolerability of polar and apolar fractions of T. polium following oral and dermal exposure in male and female Wistar rats. For the oral route, animals received 2000 mg/kg/day for 28 consecutive days, and safety was assessed using endpoints aligned with OECD TG 407, including daily behavioral observations, body-weight evolution, hematology, serum biochemistry with hepatic and renal biomarkers, and histopathology of major organs. In parallel, repeated-dose dermal exposure was conducted for 28 days under occlusive conditions in accordance with OECD TG 410, with systematic scoring of local dermal reactions and monitoring for systemic toxicity, complemented by histopathological evaluation of treated skin. Across both exposure routes, no treatment-related mortality or clinically meaningful adverse effects were detected. Hematological indices and serum biochemical markers remained within physiological ranges, and histopathological assessment revealed no extract-related lesions in examined organs or skin. Collectively, these findings indicate good short-term tolerability of the tested T. polium fractions at 2000 mg/kg/day under the present experimental conditions. Given ongoing clinical concern regarding hepatotoxicity, longer-duration studies incorporating dose–response designs and mechanistic endpoints are warranted to more definitively characterize risk.