Embryo-fetal Developmental Toxicity Study Of LN001 Administered By Intravenous Injection To Sprague-dawley Rats

The objective of this study was to evaluate the potential toxic of LN001 on pregnant female rats and the development of the embryos and fetuses following intravenous injection to the pregnant females rates once daily from implantation?Gestation Day 6,GD6?to closure of the hard palate?Gestation Day 15,GD15?.This study was to evaluate teratism in SD Rats,which get the the reference material for the clinical special people to use the new drug.LN001 was used for anesthesia and maintenance of anesthesia in clinical research.A total of 168 presumed-pregnant SD female rats were randomly assigned to 8 groups based on body weights,group 1 to 4 for toxicity study,and 5 to 8 for the toxicokinetics study.Rats were treated via intravenous injection with Control article for groups 1 and 5 or different dose level LN001 for other groups.The following parameters were evaluated during the study:clinical observations,body weights and food consumption,cesarean section,fetal external,development of the embryo and fetus,fetal skeletal,and fetal visceral.Toxicokinetics parameters were evaluated from group 5 to 8.No statistically significant changes were observed in pregnant female rats in body weight,food consumption,gravid uterus weight,number of mean corpus luteum and implantation,number of mean live fetus,number of resorption,and dead fetus,live fetus index,resorption index,and dead fetus index in different group animals,when compared with the control group.No statistically significant changes were noted in the body weight of live fetuses,placenta weight,body lengths,tail lengths,or sex ratio in different group animals,when compared with the control group.No statistically significant changes were noted in skeletal abnormality index or skeletal variation index,visceral abnormality index and visceral variation index when compared with the control group?P?0.05?.Within the design dose range in the toxicokinetics study,there was a dose-dependent increase in plasma concentrations of LN001 in rats,the dosage was increase when C_maxax and AUC_?0-360min?were increase.After ten days dosing,on GD20,there was no LN001 can detected in pregnant rats and foetus.In conclusion,LN001 was administered by intravenous injection to the pregnant female rats at three dosages once daily from GD6 to GD15for ten days.There was no embryo-fetal development toxicity and no abnormalities toxicity.