• Title/Summary/Keyword: TERATOGENICITY

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새로운 안트라사이클린계 항암제 DA-125의 생식독성연구: (I) 랫트 최기형시험 (Reproductive Toxicity Study of DA-125, A New Anthracycline Anticancer Agent: (I) Teratogenicity Study in Rats)

  • 정문구;한상섭;양중익;노정구
    • Biomolecules & Therapeutics
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    • 제2권1호
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    • pp.82-93
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    • 1994
  • DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third 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 of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.

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원방우황청심원의 랫드 최기형성에 관한 연구 (A Teratogenicity Study on Original Woo-Whang-Chung-Sim-Won in Rats)

  • 한순영;박귀례;신재호;김판기;권석철;장성재
    • Toxicological Research
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    • 제13권4호
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    • pp.331-338
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    • 1997
  • A teratogenic study on Original Woo-Whang-Chung-Sim-Won was carried out in SpragueDawley rats. Original Woo-Whang-Chung-Sim-Won suspended in distilled water was administered to pregnant dams by oral gavage during organogenesis period (from 7th to 17th day of gestation) at daily doses of 1/9, 1/3 and I pill/kg. About two-thirds of dams were sacrificed at 20th day of gestation to scrutinize the pregnant performances and fetal development, and the remaining dams were allowed to deliver. The growth, reflex, behaviour and reproductive function of F1 offsprings were examined. There was no treatment-related difference in body weight, food consumption and necropy findings of dams. No gross, skeletal and visceral abnormalities was observed in F1 fetuses from dams treated with Original Woo-Whang-Chung-Sim-Won. F1 offsprings did not show any treatment-related difference in growth, reflex, behaviour and reproductive peuformance. At caesarean section of F1 dams, no growth retardation and gross abnormality was observed in F2 fetuses. In conclusion, Original Woo-Whang-Chung-Sim-Won did not show any potential teratogenic activity in rats.

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임신토끼에 있어서 새로운 Recombinant Human Granulocyte Colony-Stimulating Factor(YHB6211)의 배.태자 발생독성평가 (Developmental Toxicity Study in the Embryos/Fetuses with a Recombinant Human Granulocyte Colony-Stimulating Factor (YHB6211) in Pregnant Rabbits)

  • 황재식;장호송;정은용;이수해;신지순;서동석;신장우;남상윤;김대중
    • Biomolecules & Therapeutics
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    • 제9권4호
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    • pp.311-317
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    • 2001
  • YHB6211, a newly developed recombinant human granulocyte colonystimulating factor, was administered at dose levels of 0, 3, 15, and 75 $\mu$g/kg/day intravenously to the pregnant New Zealand White rabbits (20 rabbits per group) during the organogenetic period, days 6 to 18 of gestation. All dams were subjected to Caesarian section on day 28 of gestation and their fetuses were examined for external, visceral, and skeletal abnormalities. No abnormalities in clinical signs, body weight changes, gross findings, mortality, and external appearance were found in all dams and fetuses exposed to 0, 3, and 15 $\mu$g/kg/day of YHB6211. However, in the group treated with 75 $\mu\textrm{g}$/kg/day of YHB6211, maternal body and uterine weights, fetal body weights and length, and the number of live fetuses were significantly decreased and further fetal mortality was remarkably increased. It is suggested that YHB6211 may have no side effect up to the dose level of 15 $\mu$g/kg/day, and there would be no teratogenicity for fetuses of rabbits up to 75 $\mu\textrm{g}$/kg/day even if it may have some toxic effects over 75$\mu\textrm{g}$/kg/day for dams and fetuses of rabbits.

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새로운 백금착물 항암제 SKI 2053R의 토끼 최기형성시험 (Teratogenicity Study of SKI 2053R, a New Platinum Anticancer Agent, in Rabbits)

  • 김종춘;김갑호;박종일;김형진;정문구
    • Biomolecules & Therapeutics
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    • 제7권3호
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    • pp.292-299
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    • 1999
  • SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.

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생약(生藥)의 최기성(崔畸性)에 관한 연구(硏究) (Teratogenicity of the Extracts of Crude Drugs)

  • 이은방
    • 생약학회지
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    • 제13권3호
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    • pp.116-121
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    • 1982
  • In order to investigate the side-effects of crude drugs, twenty drugs have been tested for the teratogenic effect in rats. Among seven drugs contained alkaloid as their ingredients, no one showed teratogenic effect, but Veratri rhizoma showed embryo-toxic as revealed by severe retardation in growth of the fetuses. The other thirteen drugs which have been used freguently in oriental medicines exhibited no teratogenic effect. Cyclophosphamide used as a reference compound showed severe malformation and retardation in the growth of rat fetuses. These findings suggest that the drug extracts adopted for the study might have no teratogenic effect in the rats.

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Sprague-Dawley 랫드에서 2-Bromopropane의 배자치사 및 최기형성 효과 (Embryo lethality and teratogenicity of 2-Bromopropane in the Sprague-Dawley rat)

  • 김종춘;오기석;신동호;김성호;김현영;윤효인;강성철;허정두;정문구
    • 대한수의학회지
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    • 제43권4호
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    • pp.657-666
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    • 2003
  • The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

Proteomic Analysis of Differentially Expressed Proteins in Human Lung Cells Following Formaldehyde Treatment

  • Jeon, Yu-Mi;Ryu, Jae-Chun;Lee, Mi-Young
    • Molecular & Cellular Toxicology
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    • 제3권4호
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    • pp.238-245
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    • 2007
  • Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.