Assessment of acute, 14-day, and 13-week repeated oral dose toxicity of Tiglium seed extract in rats

Abstract

Background Seed of mature Croton tiglium Linne, also known as Tiglium seed (TS), has been widely used as a natural product due to its several health beneficial properties including anti-tumor and antifungal activities. Despite its ethnomedicinal beneficial properties, toxicological information regarding TS extract, especially its long-term toxicity, is currently limited. Therefore, the objective of the present study was to evaluate acute and subchronic toxicity of TS extract in rats after oral administration following test guidelines of the Organization for Economic Cooperation and Development (OECD).

Methods Toxicological properties of TS extract were evaluated by toxicity assays to determine its single-dose acute toxicity (125, 250, 500, 1000, or 2000mg/kg), 14-day repeated-dose toxicity (125, 250, 500, 1000, or 2000mg/kg) and 13-week repeated-dose toxicity (31.25, 62.5, 125, 250, and 500mg/kg) in Sprague-Dawley rats and F344 rats. Hematological, serum biochemical, and histopathological parameters were analyzed to determine its median lethal dose (LD50) and no-observed-adverse-effect-level (NOAEL).

Results Oral single dose up to 2000mg/kg of TS extract resulted in no mortalities or abnormal clinical signs. In 13-week toxicity study, TS extract exhibited no dose-related changes (mortality, body weight, food/water consumption, hematology, clinical biochemistry, organ weight, or histopathology) at dose up to 500mg/kg, the highest dosage level suggested based on 14-day repeat-dose oral toxicity study.

Conclusion Acute oral LD50 of TS extract in rats was estimated to be greater than 2000mg/kg. NOAEL of TS extract administered orally was determined to be 500mg/kg/day in both male and female rats. Results from these acute and subchronic toxicity assessments of TS extract under Good Laboratory Practice regulations indicate that TS extract appears to be safe for human consumption.