• Title/Summary/Keyword: Teratogenicity

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Establishment of Short-Term Teratogenicity Study for Detecting Developmental Toxicity Induced by Gamma Radiation (방사선의 발생독성 검색을 위한 단기 최기형성 시험법의 확립)

  • 김종춘;김성호;신동호;신진영;김세라;이해준;박승춘;조성기;이윤실
    • 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.

BEHAVIORAL TERATOGENICITY OF METHAMPHETAMINE

  • Chin, Kang;Cho, Dae-Hyun;Cho, Tae-Soon
    • Toxicological Research
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    • v.6 no.2
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    • pp.121-130
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    • 1990
  • Pregnant Wister rats were given daily subcutaneous administrations of methamphetamine (MAPT; varying doses ranging from 1.0 to 4.5mg/kg) from days 7 to20 of gestation and teratogenic effects have been determined. The teratogenic effects inducible with orally administered caffeine (90mg/kg/day)for the same durations were used as the positive controls. MAPT doses greater than 2.0 mg/kg have suppressed the rate of maternal weight gain. Some of the offsprings (F1) of the prenatal MAPT treated groups had decreased growth rate and delayed development of physical characters and functional reflexes. The male offsprings of the MAPT treated groups had significant decreases in their spontaneous motor activity but had enhanced conditioned avoidance responses. However, the mating performances of these offsprings were not affected. These results indicated that prenatal exposure of MAPT may induce some behavioral teratogenicity in rats.

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TERATOGENICITY STUDY OF FOOD ADDITIVES CHEMICALS IN THE DEVELOPING CHICK EMBRYO

  • Lee, Yong-Soon;Park, Jae-Jun
    • 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.

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TERATOGENICITY STUDY OF SODIUM GLYCYRRHIZINATE IN THE DEVELOPING CHICK EMBRYO

  • Park, Jae-Jun;Lee, Yong-Soon;Ahn, Hee-Yul
    • 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.

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Effect of Ethanol on the Teratogenicity of Hypervitaminosis A in Rats (Vitamin A의 최기형성에 미치는 Ethanol의 영향)

  • Cho, Dae-Hyun;Chin, Kang;Cho, Tae-Soon
    • Journal of Food Hygiene and Safety
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    • v.5 no.4
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    • pp.229-236
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    • 1990
  • The effects of ethanol (ET) on the teratogenicity of the fat soluble drug, Vita. min A (VA) were examined in SPF Wistar rats. VA and ET were orally administered with sonde. The drugs were administered for 3 days of day 9-11 of gestation. Four groups were made; G-I control (sesame oil + saline), G-II VA $40{\times}10^{4}$ (I.Ulkg/day), G-III ET 2 (g/kg/day), G-IV $40{\times}10^{4}$ + ET 2. Congenital malformations were found G-II, G-III and G-IV. All fetuses in G-IV combination had malforamtions. Main malformation in G-IV combi. nation were microstomia, disposition of ear, open eyelids brachygnathia and cleft plate. Accordingly it might be demonstrated that the teratogenicity of hypervitaminosis A was pontentiated by concurrent ethanol in rats.

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Teratogenicity Evaluation of 2-Bromopropane Using Rat Whole Embryo Culture (랫드 전배아배양법을 이용한 2-Bromopropane의 최기형성 평가)

  • Kim Jong-Choon;Shin Dong-Ho;Kim Sung-Ho;Yang Young-Soo;Oh Ki-Seok;Jiang Cheng-Zhe;Chung Moon-Koo
    • 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.

Effects of Butylated Hydroxyanisole on Glutathione S-Transferases Activity and Cyclophosphamide-Induced Teratogenicity in Rats (랫드에서 Butylated Hydroxyanisole에 의한 Glutathione S-Transferases 유도 및 Cyclophosphamide로 유발된 기형에 대한 예방효과)

  • 강현구;이창희;이기창;이지은;김하정;최은경;윤영원;김윤배
    • Toxicological Research
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    • v.19 no.3
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    • pp.181-187
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    • 2003
  • Effects of repeated treatment with butylated hydroxyanisole (BHA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BHA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and intraperitoneally challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined. Separately, a part of rats was sacrificed for the assay of hepatic and placental GSTs activities on day 12 of gestation following 7-day treatment with BHA. Cyclophosphamide, administered on day 12 of gestation, induced 43.2% of fetal death and resorption, and 100% of malformations in live fetuses, in contrast to low fetal resorption (8.7%) and malformations (8%) in control group. The malformations include cranial defect and exencephaly (100%), micrognathia and tongue extrusion (100%), limb defects (40%), renal pelvic dilatation (39%), and cleft palate (15%). Interestingly, BHA induced GSTs activities by 62% and 46% over the control in liver and placenta, respectively, and remarkably reduced the fetal resorption (13.9%) and malformations, resulting in 62% of cranial defect and exencephaly, 68% of micrognathia and tongue extrusion, 29% of limb defects, and 14% of renal pelvic dilatation. Taken together, it is suggested that a long-term pretreatment with BHA could substantially prevent fetuses from abortion and malformations following intrauterine exposure to teratogens including cyclophosphamide by inducing phase II antioxidant enzymes such as GSTs.

Teratogenicity Study of KTC-1, a New Semisynthetic Rifamycin Derivative, in Rats (새로운 반합성 Rifamycin 유도체 KTC-1의 랫트 최기형 시험)

  • 김종춘;정문구;박종일;한상섭
    • 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.

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Studies on the teratogenicity of folpet in the developing chick embryo (계태아를 이용한 농약(folpet)의 기형독성 연구)

  • Lim, Yoon-kyu;Heo, Gang-joon;Lee, Yong-soon
    • Korean Journal of Veterinary Research
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    • v.34 no.2
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    • pp.375-379
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    • 1994
  • A teratogenicity test of 'folpet' was carried out in the developing chick embryos to investigate and validate the safety of rural environmental hazardous materials. Folpet was administered to chick embryos' yolk sac at a rate of 0.1mg and 0.01mg per SPF eggs at 96 hours of incubation. The morphological changes were examined. Fertility ratio of SPF eggs used was 94.9%. Hatching rate of untreated control group was 74.4% and the group dosed with 100ul of corn oil into the yolk sac was 70.0%. The $LD_{50}$ of folpet was 0.663mg/100ul/egg. After hatching, mean body weight, body length, claw length and beak length of high and low dose administered groups were not significantly different from untreated and vehicle control group. There was no abnormal appearence in all the groups. Therefore it seems that, within the doses applied, folpet dose not induce potential teratogenicity in the developing chick embryos.

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