Safety Assessment of Cistanche tubulosa Extract: Genotoxicity and Repeated Dose Toxicity Tests

Cistanche tubulosa (CTE) aqueous extract is already employed as a botanical prescription drug for treating dementia in China. CTE, derived from dried C. tubulosa stems, is freshly prepared with sterile distilled water. CTE requires acute and chronic toxicity studies to ensure its safety in clinical applications. This study evaluates the safety profile of CTE through both in vitro and in vivo tests. Ames tests conducted on five strains of Salmonella typhimurium showed no increase in reverse mutations following exposure to CTE. Micronucleus tests in mice indicated that CTE (0.5 - 2 g/kg) did not cause genetic damage in blood-forming cells. In acute studies, mice were administered CTE orally at doses of 2, 4, and 8 g/kg for 14 days, with controls receiving water as the vehicle. Chronic oral toxicity was evaluated over 6 months in rats and dogs at doses of 1.65 g/kg and 1.5 g/kg, respectively, to identify toxicity thresholds and calculate safety margins relative to the clinical dose. Results demonstrated that CTE administration, ranging from the no-observed-adverse-effect level (NOAEL) to the high-dose ceiling, induced no mortality, with all physiological parameters remaining within homeo-static ranges. These data provide a critical framework for defining the safety margin in human clinical translation.