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OBJECTIVE: To establish the background data on SD rat embryo-fetal development toxicity studies by Shanghai Institute of Planned Parenthood Research (National Evaluation Center for Toxicology of Fertility Regulating Drugs), and provide reference for reproductive toxicology research. METHODS: From the embryonic-fetal developmental toxicity tests of SD rats between 2010 and 2018, the index data on embryo development and fetal growth and development of pregnant rats was selected, including pregnancy body mass and pregnancy outcomes (average of corpora lutea, implantation, live fetuses, absorptions and dead fetuses), the growth and development of fetuses (fetal body mass, body length and tail length) and fetal appearance, viscera, and skeleton. The data was statistically analyzed, and the mean, standard deviation and coefficient of variation were calculated. RESULTS: Totally 217 pregnant rats and 2506 fetuses were included. The body mass of pregnant rats on gestation day 0 (GD0) was (222±22) g, while the food consumption of GD0-1was (18.9±3.8) g·d-1. The body mass of GD20 was (353±30) g and the food consumption of GD19-20was (26.2±4.0) g·d-1. GD20euthanasia cesarean section examination showed that the pregnancy rate was 95.2%, and that the average of corpora lutea, implantation and live fetuses was 12.8±2.1, 11.8±2.8 and 11.5±2.8, respectively. The rate of live fetuses and absorption rate was 97.9% and 2.1%, respectively. Among the fetal development indexes, the body mass and placental mass were 3.6±0.3 and (0.5±0.1) g, respectively. The body length was (35.7±1.5) mm, the tail length was (12.9±0.4) mm, and the sexual ratio (male/female) was 1.0 (1227/1279). The external, visceral and skeletal variations were 0.2%, 0.5% and 7.4%, respectively. CONCLUSION: The background data on embryo-fetal toxicity studies of SD rats has been established, which can provide reference for reproductive toxicity research.
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OBJECTIVE To summarize the data on embryo-fetal developmental toxicity study of rabbits, and to establish the background data so as to provide reference for drug reproductive toxicology research. METHODS From the embryo-fetus developmental toxicity study of rabbits in our laboratory between 2011 and 2018, all the data on control groups was selected, including rabbits' pregnancy mass, outcomes of pregnancy (the average number of corpus lutea, implantation, live fetuses, fetal absorption rate, fetal live rate, fetal absorption rate), fetal growth and development (mass, crown-rump length and tail length) and fetal variation (appearance, viscera and skeleton). The mean and standard deviations of each index were calculated. RESULTS The embryo-fetal development indexes of 149 pregnant rabbits and 1097 fetuses were summarized. The gestational age of rabbits was about 3-5 months, and the body mass was (3.0±0.3) kg on gestation day 0 (GD0), and (3.5±0.4) kg on GD28. These rabbits were euthanized and cesarean section examination showed that the pregnancy rate was 85.6%, the average of corpus lutea number was 8.0±2.1, the average number of implantations was 7.6±2.1, the average number of live fetuses was 7.4±2.1, the live rate was 96.2%, the absorption rate was 1.9%, and the death rate was 1.8%. Among the fetal development indicators, fetal body mass was (33.4±5.0) g, placental weight was (4.0±0.8) g, crown-rump length was (86.3±5.9) mm, tail length was (11.3±0.8) mm, and sex ratio (male/female) was 1.0 (550/547). The rate of appearance variation (or malformation) was 0.18%, skeleton variation (or malformation) was 33.5%, and visceral variation (or malformation) was 0.09%. CONCLUSION The background data of the embryo-fetal developmental toxicity study of rabbits is established in our laboratory. The changes of each index are stable, and the spontaneous deformity rate of fetuses is low.
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@#Carenoprazan has the similar structure and mechanism with the potassium-competitive blocker vonoprazan. Howerver, its safety during the pregnancy remains uncertain. To study the embryo-fetal development toxicity and toxicokinetics of carenoprazan hydrochloride via oral administration, time-mated Sprague-Dawley rats were divided into 5 groups, treated with normal saline, cyclophosphamide for injection(3. 8 mg/kg), and carenoprazan hydrochloride(20, 60, 200 mg/kg), respectively. Administrated orally from gestation day(GD)6 - 15. At the termination(GD 20), pregnant dams were sacrificed, and concentrations of carenoprazan hydrochloride as well as its metabolite in plasma and issues of both maternal and fetus were examined. As a result, the body weight gain of maternal in both high(200 mg/kg)and medium(60 mg/kg)dose as well as the food consumption of high-dose were decreased during GD 10-16. At the high dose group, decrease of crown rump length of fetuses were significant. Also, skeletal malformation/variations of fetus increased obviously at both high- and medium- dosage. The toxcicokinetics of carenoprazan hydrochloride are linear after single treatment between 20-200 mg/kg. The placental barrier was penetrated by carenoprazan hydrochloride and metabolite, and the distribution of metabolite in organs were similar in both maternal and fetus, with the highest concentration in livers. Therefore might resulted in the development toxicity. The No Observed Adverse Effect Level(NOAEL)of carenoprazan hydrochloride for both maternal and fetal was 20 mg/kg.
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Objective To investigate teratogenicity on the zebrafish embryo and genetoxicity induced by Sodium Pentachlorophenate (NaPCP),and to provide suggestions for protecting the environmental safety and human health. Methods Zebrafish embryonic development test,p53 gene in zebrafish eggs mutagenicity test,Vicia Faba Micronucleus Test and Ames test were used in the studies.Results The results of zebrafish embryonic development test showed that NaPCP increased embryonic 120 hpf teratogeny rates and 120 hpf death rates and decreased embryonic 120 hpf hatching rates in concentration of 0.5 -2.5 μL/L,with significant teratogenic effect on the embryo.The rates of embryo abnormity increased with the exposure time and concentration.Sequence analysis showed that NaPCP exposure group zebrafish p53 gene had mutated at the concentration of 0.4 μL /L.The base substitution of AAT→AAG at codon 49,ACA→ACG at codon 87 and GCG→GCA at codon 158 were detected by PCR -directed sequencing.This may result in the Asn→Lys of expressed p53 protein.As compared with control group,0.2 mg/L,1.0 mg/L dosage of NaPCP could induce an extremely significant increase in micronucleus frequency of vicia faba root tip cells and had a certain dose -effect relationship.Ames test was negative.Conclusion NaPCP could delay embryonic development and even cause embryonic lethality and induce abnormality in zebrafish.NaPCP had certain genetoxicity.
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OBJECTIVE: To observe the toxicity effect of realgar on rat fertility and early embryo development. METHODS: Male and female SD rats were divided into control group, realgar low (50 mg · kg-1), medium (125 mg · kg-1) and high (250 mg · kg-1) dose groups. Realgar (batch No. H2007052401) was given by i.g. daily to male rats from six weeks before mating until the successful mating day and to females from two weeks before mating until the sixth day of pregnancy. Male rats were sacrificed after mating, and female rats were sacrificed on the 15th day of pregnancy. The numbers of corpus luteum, implantation spot, and survival fetus were recorded. Histopathological examination was carried out. Statistical analysis was done to compare with the control group. RESULTS: The mating rates, pregnancy rates, live fetus rates, loss rates before and after implantation, the number of corpus luteum, the number of implantations and reproductive organs in realgar groups were not significantly different when compared with the control group. Histopathological examination showed that there were micro-vacuolization in liver cells, focal infiltration of mononuclear cells and steatosis in liver in some female rats (3/10) and male rats (1/10) in realgar high-dose groups. And some female rats (2/10) in realgar high-dose group had interstitial fibroblasts proliferation with lymphocyte infiltration and focal renal tubular basophilic change. CONCLUSION: Realgar has no significant toxicity effect on rat fertility and early embryo development, but has certain toxicity to liver and kidney.
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Objective To study the effects of di-butyltin dilaurate (DBTD) exposure on pregnancy outcome in Wistar rat and evaluate it's effect on sexual development of fetuses. Methods Timed pregnancy rats were treated with corn oil or DBTD (10, 20, 30 mg/kg body weight) from days 12-19 of gestation. On gestational day (GD) 20, dams were sacrificed to investigate the pregnancy outcome. Results There was a downtrend in weight of dams on GD20 as the DBTD exposure dose increased. The weight of dam's utero significantly decreased in 30 mg/kg group. A significant decrease in fetal weights was observed in all DBTD groups, and fetal sizes in 20, 30 mg/kg groups. Exposure to DBTD from GD 12-19 resulted in a distinct increase in normalized anogenital distances in female fetuses, but no effects were seen in male ones. DBTD exposure did not result in external malformations, however, delayed ossification of fetal phalanges was observed in all DBTD treated groups. Dead fetuses and absorbed embryos were observed in 20, 30 mg/kg DBTD groups. Conclusion The results of the present paper show that DBTD exposure has some adverse effects on fetal development and may exert a masculinizing effect on female fetuses.