Reproductive and developmental toxicity study of caffeic acid in mice.

Caffeic acid is an antioxidant commonly used to promote hematopoiesis and hemostasis. However, little is known about its systemic safety profile in reproduction and development. Here, we focused on the reproductive and developmental toxicity of caffeic acid in F0 female mice and F1 offspring. In the three-segment study, the F0 female mice were continuously exposed to 0, 0.15, 5 or 150 mg/kg/day of caffeic acid by gavage. We found that 5 mg/kg/day and 150 mg/kg/day of caffeic acid affected implantation of embryos when administered before gestation day 6. In addition, 150 mg/kg/day of caffeic acid affected fetal weight gain. No maternal toxicity, fetal teratogenesis or post-natal effects on pup development were observed. The no-observed-adverse-effect-level was 0.15 mg/kg/day for pregnant mice under the conditions of this study.