Acute and 28-Day Repeated-Dose Oral Toxicity of a Standardized Aleurites moluccanus Leaf Extract in Rodent and Non-Rodent Models.

ETHNOPHARMACOLOGICAL RELEVANCE: Aleurites moluccanus is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory processes in general. The A. moluccanus leaves extract has been extensively studied confirming its properties and pointing it out as a potential phytomedicine to treat pain and inflammation. However, appropriate toxicity tests are necessary to better establish the A. moluccanus safety profile to allow the inclusion of the standardized extract in subsequent clinical trials. AIM OF THE STUDY: This study evaluated the acute and 28-day repeated-dose oral toxicity of a standardized A. moluccanus leaf extract in rats and minipigs, following OECD guidelines. MATERIALS AND METHODS: A. moluccanus was orally administered to rats and minipigs to evaluate the effects in the acute and 28-days sub-acute toxicity assays. Toxicological parameters were checked, including general observations, organ/body weights, food consumption, hematological and serum biochemical values and histopathological findings. RESULTS: Acute toxicity studies showed low toxicity in both species, with an LD50 greater than 5000 mg/kg in rats and greater than 1000 mg/kg in minipigs. In the 28-day repeated-dose study, male rats showed mild, non-dose-dependent reductions in body weight gain at 250 and 1000 mg/kg/day, without corroborating clinical, biochemical, or histopathological alterations; a NOAEL of 2000 mg/kg/day, the highest dose tested, was established for rats. In minipigs, the highest dose (350 mg/kg/day) induced mild gastric mucosal inflammation, identifying the stomach as the primary target organ and establishing a NOAEL of 200 mg/kg/day. The lower minipig NOAEL was used to estimate a Maximum Recommended Starting Dose of approximately 18.9 mg/kg/day for humans. CONCLUSIONS: These findings indicate a favorable preclinical safety profile for the standardized extract in both rodent and non-rodent species, providing a foundation to support its continued development toward clinical trials.