Long-term toxicity studies in dogs support the safety of the special extract ERr 731 from the roots of Rheum rhaponticum

The special extract ERr 731 from the roots of rhapontic rhubarb has been regularly prescribed for women with menopausal symptoms since 1993. As its constituents belong to the class of natural hydroxystilbenes, concerns have been raised about possible health risks similar to those known for the estrogenic diethylstilbestrol. To demonstrate the safety of the medical use of ERr 731, the extract was tested in long-term toxicity studies in dogs.In two independent studies, male and female beagle dogs were treated with 100, 300 and 1000 mg ERr 731/kg body weight (bw)/day and observed for 4 and 13 weeks followed by recovery periods. A histopathological examination of a full set of organs of all animals was examined.In both studies, all animals survived the scheduled treatment and recovery periods. The administration of ERr 731 resulted in increased incidences of feces with white particles due to an incomplete absorption of the extract. In the 13-week study, a slight decrease in glucose levels was recorded in both sexes at 1000 mg/kg bw/day. All other clinical changes were marginal and not related to ERr 731. Importantly, there was no increase in weight of organs of the genital tract due to ERr 731 intake. Based on these results, the no-observed-adverse-effect-level is 1000 mg/kg bw/day. No pathological findings where detected following ERr 731 treatment demonstrating that the toxicological risk for women taking ERr 731 regularly is extremely low.