Oral dose-ranging developmental toxicity study of an herbal supplement (NT) and gallic acid in rats.

Objective: To evaluate the combination of rhubarb, astragalus, red sage, ginger, and turmeric (mixture referred to as "NT") together with gallic acid for evidence of reproductive toxicity in rats.

Methods: Fifty virgin female rats were cohabited with male rats. Day 0 of potential pregnancy was evidence of spermatozoa on vaginal smear. The presumably pregnant rats were randomized to five groups of 10 individuals and were fed by daily gavage on days 6-20 of presumed gestation with one of the following: deionized water placebo, 21.6 mg/kg per day, 215 mg/kg per day, 430 mg/kg per day, or 860 mg/kg per day of a mixture of NT (20%) and gallic acid (80%). Cesarean section was performed on day 21.

Results: All 50 rats had one or more live fetuses and survived until they were killed. Body weight was reduced in the 860 mg/kg per day group compared with placebo: mean (SD), 406.8 (23.0) vs. 430.1 (27.7) g, P<0.05. There were no dose-related adverse events or differences between groups in uterine size, food intake, corpora lutea, implantations, litter size, number of live fetuses, and gender distribution of fetuses or fetal resorptions. There were no dead fetuses, and all placentae appeared normal. All rats and tissues were normal at necropsy. Fetal weights did not differ between groups, and there were no fetal abnormalities.

Conclusion: The combination of NT and gallic acid gave no evidence of reproductive toxicity at 430 mg/kg per day or below, which is reassuring should this combination be used in the future as a dietary herbal supplement for the treatment of obesity.