• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.81-86
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• 2006

Embryotoxicity tests were performed in Daphnia magna to assess aquatic ecotoxicity of bisphenol A, a well known industrial compound showing estrogen-like activity in vivo, and to examine their effectiveness in the toxicological assessment. The whole embryonic developmental period was classified into 6 stages and developmental abnormality was checked to evaluate the embryotoxicity. In the present study, bisphenol A showed the ability to interfere with embryonic development, suggesting its antiecdysteroidal activity. The rates of mortality, delayed development, deformity and immobility all showed good concentration-response relationship, demonstrating their possibility as useful toxicological indices in daphnid embryotoxicity tests that have been rarely performed so far. It seemed favorable to the test sensitivity that embryos are removed from maternal daphnids around 7 hr after deposition from the ovaries to the brood chamber. These results suggest that daphnid embryotoxicity tests can be one of useful tools available for the assessment of ecotoxicity of various chemicals in the aquatic environment.

• Toxicological Research
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• v.11 no.1
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• pp.31-36
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• 1995

Cyclophosphamide (CP) must be enzymatically activated by cytochrome P450(CYP)-linked mixed-function oxidation pathway to be either mutagenic or teratogenic. Influences of alterations in hepatic mixed-function oxidase acitivity and glutathione (GSH) content on the embryotoxicity of CP were studied in rat whole embryo culture system. The embryotoxicity of CP was compared using rat S-9 fraction (S-9) pretreated with chemicals inducing different CYP isozymes, acetone (ACE), Aroclor 1254 (ARO), $\beta$-naphthoflavone (NAF) and phenobarbital (PHE). When 10.5 day embryos were cultured in the immediately centrifuged rat serum for 48 hrs using general gas char{ging schedule, CP$(40{\mu}g/ml)$ with S-9 induced by either NAF or PHE increased the incidence of realformations and significantly decreased embryonic growth compared with the non-induced S-9 group. ACE or ARO induced S-9 group showed no significant difference in embryonic growth. These data suggest that PB and/or NAF inducible CYP isoenzymes are mainly involved in the activation of CP. To examine the effect of GSH on the embryotoxicity of CP, 10.5 day embryos were exposed to CP and S-9 after preincubation with 10 mM of GSH for 3 hrs. In the GSH pretreated group the growth of embryos increased significantly compared with that of the untreated group, suggesting that GSH may protect embryos in culture from some toxic effects of CP.

• Toxicological Research
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• v.12 no.2
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• pp.223-230
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• 1996

The increased embryotoxicity of the antifolate drug pyrimethamine (PYM) with concomitant dietary dosing of folic acid (FA) was examined in mice. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (pyrimethamine 80 ppm), PYM II (pyrimethamine 150 ppm), PYM II+FNA (pyrimethamine 150 ppm and folinic acid 12 mg/kg/day), PYM II+FA (pyrimethamine 150 ppm and folic acid 350 ppm), FA (folic acid 350 ppm) and a control group. The agents were administered for 7 days from day 6 throughout 12 of gestation. PYM and FA were administered with mashed feed and FNA was intraperitoneally injected. The high incidence of fetal realformations was observed in the PYM II group; these included kinky tail, open eyelids, club foot, cleft palate, absence of the pulmonary lobe, diaphragmatic hernia, fused sternebrae, fused cervical or thoracic vertebral arch, among others. All embryos of the PYM II+FA group were resorbed. No realformed fetuses were observed in the PYM II+FNA group. These results show that the concomitant dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also observed.

• Toxicological Research
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• v.13 no.1_2
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• pp.95-101
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• 1997

Ethyl carbamate (EC) is a potent teratogen in rodents and is present at low concentration in fermented foods and alcohol beverages. It has been well hypothesized that some metabolic products are responsible for the teratogenic effects of the compound. In the present study, the effects of phenobarbital (PB) on EC-induced embryotoxicity were investigated in SD rats. Six groups were constructed: EC 300 (EC 300 mg/kg/day), EC 600 (EC 600 mg/kg/day), EC 600+PB (EC 600 mg/kg/day and PB 80 mg/kg/day), PB (PB 80 mg/kg/day), DR (dietary restriction, 8 g/day/rat) and a control group. Rats of the EC 600+PB group were pretreated with phenobarbital intraperitoneally for three days to induce cytochrome P450 enzymes, followed by oral administration of EC for two consecutive days. The incidence of fetal deaths in the EC 600+PB group was higher than that of the EC 600 group(42.7 vs. 14.3%). The incidence of fetal realformations in the EC 600+PB group was higher than that of the EC 600 group (external; 7.0 vs. 4.1%, visceral; 31.4 vs. 11.3%, skeletal; 11.1 vs. 6.5%). There was no embryotoxicity in the control, EC 300, PB and DR groups. These results show that the pretreatment with phenobarbital augments EC-induced embryotoxicity in rats, indicating an evidence that metabolic activation by cytochrome P450 may be the major pathway of EC to its embryotoxic forms.

• Journal of Environmental Health Sciences
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• v.28 no.4
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• pp.17-22
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• 2002

In crustaceans, as in other arthropods, the molt cycle and the physiological process of growth are controlled by molting hormones (MH) which are steroid hormones, the ecdysteroids. Ecdysteroids are major arthropod hormones which control both development (embryonic and larval molts, metamorphosis) and reproduction. The purpose of the present study was to evaluate both fenarimol and methoprene for embryotoxicity to daphnids. The embryotoxicity associated with each compound was assessed to discern whether the embryotoxicity of methoprene might be due to ecdysone agonist and the ecdysone antagonistic effects of fenarimol on Daphnia embryo. Exposure of daphnids for three weeks to 50 M methoprene resulted in a significantly high incidence of offspring that exhibited general toxicity. This exposure concentration had significant effects on the overall number of embryo death. However, exposure to 3 or 1 $\mu$M fenarimol were no significant effects on the embryo toxicity. The incidence of both of these toxicity increased with methoprene exposure. This observation suggest that methoprene showed embryonic general toxicity during embryo development, while, only fenarimol showed weak general toxicity with early stages of embryonic development.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.601-607
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• 1994

This study was carried out to investigate the potential of phenol to induce embryotoxicity in the Sprague-Dawley rat. Seventy mated rats were distributed among three treated troups, a vehicle control group and a negative control group. Phenol was at dose levels of 20, 60 and 180mg/kg/day adminsistered by gavage to pregnant rats three times per day from days 7 to 12 of gestation. All dams were subjected to the caesarean section on day 20 of gestation. At 120mg/kg, dams exhibited decreased locomotivity. In addition, both weight reduction and retarded ossification of fetuses were observed. There were no signs of maternal toxicity or embryotoxicity at 20 and 60mg/kg. The results show that phenol induces fetal growth retardation at maternally subtoxic dose in rats.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.10
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• pp.1282-1290
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• 2010

The study was carried out to assess the developmental abnormalities induced by Cytotec in mice during intrauterine life. Pregnant mice were exposed to a single dose of 0, 0.02, 0.04, 0.06, 0.08 and $0.1{\mu}g$/g BW on day 8 of gestation. Fetuses were recovered on day 18 of gestation. These fetuses were subjected to morphological and morphometric studies. Morphological studies showed abnormalities like anophthalmia, microophthalmia, micromelia and syndactyly. In addition to these, resorptions were also encountered in the higher dose groups. Morphometric analysis showed an overall reduction in body weight, crown rump length, brain and eye circumference, pinna and snout size, length of fore and hind limb and tail size with a significant difference (p<0.001) compared to controls. The outcomes of histological studies revealed some brain defects like hydrocephaly, enlarged third ventricle and undifferentiated ectoneural cells and abnormalities of the heart included right auricle thrombosis and degeneration of trabecular zone.

• YAKHAK HOEJI
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• v.42 no.3
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• pp.336-344
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• 1998

Effects of ochratoxin A (OTA) on embryo development were studied in cultured whole embryos from 9.5 day gestation rat for 48 h. OTA (more than $0.5{\mu}g/ml$) induced microcephaly in the cultured rat whole embryos. Protein and DNA content, and DNA synthesis were significantly inhibited by OTA. We next examined whether the microcephaly seen in cultured whole embryo partially results from inhibition of differentiation of embryonic midbrain cells. Embryonic midbrain cells were extracted from 12 day gestation rat embryos, and cultured for 96 hr. OTA ibhibited cell differentiation about 50% over control. We also tested whether OTA-induced embryotoxicity would be associated with oxidative damages. We measured the ${\gamma}$-glutamyltranspeptidase (${\gamma}$-GT) and glutathione peroxidase (GPX) activities, and glutathione (GSH) content in both cultured whole embryos and embryonic midbrain cells. OTA decreased GSH content, whereas slightly increased ${\gamma}$-GT activity, but GPX activity was not significantly changed. These results show that OTA caused the microcephaly and its effect may be partially due to the inhibition of cell differentiation of embryonic midbrain cells, but the role of oxidative damages is not clear in embryotoxicity.

• Korean Journal of Veterinary Research
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• v.34 no.1
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• pp.165-172
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• 1994

DA-125 is a new anthracycline antitumor antibiotic, which is derived from adriamycin. The potential of DA-125 to induce embryotoxicity was evaluated in the Sprague-Dawley rats. One hundred twenty naturally mated SD rats(sperm in vaginal lavage=day 0) were distributed among three treated groups and a control group. DA-125 was administered intravenously at dose levels of 0. 0.1, 0.3 and 1.0mg/ kg/day. Dams were treated from day 7 to 17 of gestation and were subjected to the caesarean section on day 20. At 1 mg/kg, reduced food intake, reduced body weight and decreased weight of spleen were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. Characteristic malformations include exencephalia, gastroschisis, cleft lip, dilatation of lateral and 3rd ventricle, fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3mg/kg. The results show that the test agent DA-125 is embryotoxic at maternally subtoxic dose in rats.

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.70.2-70.2
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• 2008