Developmental and reproductive toxicity studies of Hydroxysafflor Yellow a in Sprague-Dawley rats

This study aimed to evaluate the developmental and reproductive toxicity of HSYA across three segments (FEED, EFD, and PPND). HSYA was administered intravenously to Sprague-Dawley (SD) rats at doses of 25, 75, or 250 mg/kg. FEED: In the 250 mg/kg/day group, body weights of F0 males decreased during weeks 2, 3, and 4 post-administration. Several males in the high-dose group exhibited yellow-red ocular secretions from day one to week seven, which resolved thereafter. EFD: No significant differences were observed in the incidence of malformations or variations in the F1 generation. Fetal body length in the 25 mg/kg group was significantly greater than in the control group. Toxicokinetic analysis revealed that HSYA can cross the placental barrier. PPND: No significant abnormalities were observed in either F0 or F1 generation rats. The survival rate of F1 offspring was significantly higher, and F1 mortality rate was significantly lower in the 25 mg/kg/day group. Toxicokinetic data confirmed that HSYA also crosses the blood-milk barrier. Based on these findings, the no-observed-adverse-effect level (NOAEL) for HSYA was determined to be 250 mg/kg/day. Overall, these results provide valuable reference data for human clinical dosing.