• Toxicological Research
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• v.20 no.2
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• pp.117-122
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• 2004

The present study was carried out to establish a short-term teratogenicity study for detecting developmental toxic potential induced by gamma radiation in ICR mice. Pregnant mice were exposed at dose levels of 0, 0.5, 1, 2, or 4 Gy on gestational day 8.5. All dams were subjected to caesarean section on gestational day 10.5 and their embryos were examined for growth, differentiation, and morphological abnormalities. An increase in the number of resorption was found at 4 Gy in a dose-dependent manner. Dose-dependent decreases in the developmental score of yolk sac circulation and olfactory system at above 1 Gy, in the number of somite pairs and developmental score of allantois, optic system, and maxillary process at above 2 Gy, and in the all growth and developmental parameters examined at 4 Gy were found. Various types of morphological abnormalities were seen at dose levels of 0.5 Gy or greater. Characteristic malformations induced by gamma radiation were abnormal axial rotation, hematoma, craniofacial hypoplasia, open neuropore, shortened prosencephalon, kinked somites, irregular somites, swelling, hydropericardium, absent branchial bar, and absent limb bud. Morphological alterations such as hematoma, craniofacial hypoplasia, open neuropore, and kinked somites were noted even in the lowest dose (0.5 Gy). These results indicated that the short-term teratogenicity study established in this study can be a useful tool for not only detecting the developmental toxic potential induced by gamma radiation, but also screening radio-protective agents in ICR mice.

• Toxicological Research
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• v.5 no.1
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• pp.61-69
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• 1989

To evaluate possible teratogenicity of food additives such as sodium propionate and monosodium glutamate, 300 haching eggs were subjected to potential mutagenicity assay by administration of low and high doses of the materials via york and air sac. The results are summarized as follows: 1. Mortality rate of chick embryo was increased significantly by dosage related in the group of sodium propiorate and monosodium glutamate when compared to placebo and non-treated group. 2. Frequency of embryo with malformation in treated group was not increased significantly when compared to placebo and non-treated group.

• Toxicological Research
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• v.5 no.2
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• pp.167-171
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• 1989

Potential teratogenicity of sodium glycyrrizinate in developing chick embryo was investigated. Body length was shortened significantly by dosage related when compared to untreated and vehicle control, but there was no significant difference on body weight, hind-limb length, claw length in all of the groups.

• Toxicological Research
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• v.11 no.1
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• pp.81-89
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• 1995

A teratogenicity study of KTC-1, a new semisynthetic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 7, 21, and 63 mg/kg/day were administered to darns orally gayage from day 7 to day 17 of gestation. Two-third of dams per group were subjected to cesarean section on day 21 of pregnancy for examination of their fetuses, and the remaining one-third of darns per group were allowed to deliver naturally for postnatal examination of their offspring. At 21 mg/kg/day, an increase in the skeletal variations of F1 fetuses and a decrease in the body weight of F1 offspring were seen. At 63 mg/kg/day, a loss in body weight was observed in darns. An increase in fetal death rate, a decrease in litter size and body weight, and an increase in the incidence of visceral malforrnations and skeletal variations were found in F1 fetuses. In particular, lumar rib occurred at an incidence of 31%. In addition, an increase in the dead newborns at birth and neonatal deaths during the lactation period, a loss in body weight, and a decrease in spleen weight were observed in F1 offspring. There were no signs of maternal toxicity or embryotoxicity at 7 mg/kg/day. The results suggest that the no-effect dose level(NOEL)for dams is 21 mg/kg/day, and NOELs for F1 fetuses and offspring are 7 mg/kg/day.

• Toxicological Research
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• v.22 no.2
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• pp.127-133
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• 2006

Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.151-158
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• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.47-53
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• 1995

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.2, 0.6 and 1.8 mg/kg/day intravenously to pregnant New Zealand White rabbits from day 6 through 18 of gestation. The does were subjected to the caesarean section on day 28 of gestation. Effects of test agent on general toxicity of does and embryonic development of F1 fetuses were examined. At 1.8 mg/kg, the organ weight for ovary of does was significantly decreased. The decrease in the number of corpus lutea, implantations and litter size, and the increase in the rate of resorptions were also observed. In addition, various types of external, visceral and skeletal malformations occurred in fetuses at an incidence of 7.7, 7.7 and 20.6%, respectively. The results show that the no effect dose levels (NOELs) of DA-125 are 0.6 mg/kg/day for does and F1 fetuses.

• Toxicological Research
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• v.9 no.1
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• pp.61-67
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• 1993

LBD-005, a newly developed recombinant granulocyte-macrophage colony-stimulating factor, was at dose levels of 0, 20, 80 and 320ng/kg/day administered subcutaneously to pregnat New Zealand White rabbits during the organogenetic period. The dams were subjected to caesarean section on day 28 of pregnancy. Effects of test substance on dams and embryonal development of fetuses were examined. No treatment-related changes in clinical signs and necropsy findings of dams were observed in all groups. At 80 and 320 ng/kg, a significant decrease in food consumption followed by a loss in body weight was found.

• Toxicological Research
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• v.9 no.1
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• pp.99-105
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• 1993

LBD-007, a newly developed recombinant human interferon alphaA, was at dose levels of 0.3 $\times$$10^6$ , 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subcutaneously to pregnant New Zealand White rabbits during the organogenetic period. Cyclophosphamide was used as a positive control. All pregnant females were subjected to the caesarean section on day 28 of pregnancy. Effect of test substance on dams and embryonal development of fetuses were examined. 1. No treatment-related changes in clinical signs, food consuption, body weight and necropsy findings of dams were observed.

• Toxicological Research
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• v.9 no.1
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• pp.83-98
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• 1993

LBD-007, a newly developed recombinant human interferon alpha A, was at dose levels of 0, 3 $\times$ $10^6$, 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subctaneously to pregnant Sprague-Dawley rats during the organogenetic period. Ethylenethiourea was used as a positive control. 2/3 of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. 1. No treatment-related changes in clinical signs, food consumption, body weight and necropsy findings of dams were observed.