The Zishen Yutai pill shows no reproductive toxicity on embryo-fetal development in rats and rabbitsElectronic supplementary information (ESI) available: ESI Table 1: Doses of ZYP and its controls used in this study. See DOI: 10.1039/c4tx00145a

Objective : the Zishen Yutai pill (ZYP) is one of the most commonly used Chinese medicines to prevent miscarriage. However, its safety during pregnancy remains ill-defined. In this study, we aimed to investigate the potential reproductive toxicity of ZYP on embryo-fetal development. Methods : various doses of ZYP were given to pregnant rats (6, 12 and 24 g kg −1 d −1 ; i.e. 24×, 48× and 96× clinical doses) and rabbits (1.5, 3.0 and 6.0 g kg −1 d −1 ; i.e. 6×, 12× and 24× clinical doses) by intragastric administration for the period from implantation to hard palate closure. Physiological saline and cyclophosphamide were used as negative and positive controls, respectively. Maternal effects on weight loss, implantation failure and fetal resorption as well as effects on fetal physical growth and congenital malformations were recorded. Results : both maternal and fetal toxicities were observed in rats and rabbits after cyclophosphamide exposure, including lower maternal weight (not in rabbits), decreased rate of live fetuses, increased rate of fetal resorption, inhibited fetal physical growth and higher rate of malformation. However, adverse effects such as significantly lower extra-uterine weight gain and decreased food intake during GD 6-7 were only detected in rats after exposure to ZYP at the dose of 24 g kg −1 d −1 , while no severe effects were found in all ZYP treated rabbits. Conclusions : ZYP exhibited no reproductive toxicity on embryo-fetal development at the dose of 12 g kg −1 d −1 for rats and 6 g kg −1 d −1 for rabbits. Consequently, ZYP can be safely used at the clinical dose. High dose of Zishen Yutai pill (ZYP) showed mild maternal toxicity in rat (24 g kg −1 d −1 , 96× clinical dose) and no reproductive toxicity in rabbit (6 g kg −1 d −1 , 24× clinical dose). ZYP could be safely used at the clinical dose during pregnancy.