• Title/Summary/Keyword: Fetal toxicity

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Predicting fetal toxicity of drugs through attention algorithm (Attention 알고리즘 기반 약물의 태아 독성 예측 연구)

  • Jeong, Myeong-hyeon;Yoo, Sun-yong
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2022.05a
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    • pp.273-275
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    • 2022
  • The use of drugs by pregnant women poses a potential risk to the fetus. Therefore, it is essential to classify drugs that pregnant women should prohibit. However, the fetal toxicity of most drugs has not been identified. This takes a lot of time and cost. In silico approaches, such as virtual screening, can identify compounds that may present a high risk to the fetus for a wide range of compounds at the low cost and time. We collected class information of each drug from the hazard classification lists for prescribing drugs in pregnancy by the government of Korea and Australia. Using the structural and chemical features of each drug, various machine learning models were constructed to predict fetal toxicity of drugs. For all models, the quantitative performance evaluation was performed. Based on the attention algorithm, important molecular substructures of compounds were identified in the process of predicting the fetal toxicity of the drug by the proposed model. From the results, we confirmed that drugs with a high risk of fetal toxicity can be predicted for a wide range of compounds by machine learning. This study can be used as a pre-screening tool for fetal toxicity predictions, as it provides key molecular substructures associated with the fetal toxicity of compounds.

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Historical Control Data for Developmental Toxicity Study in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 발생독성시험의 기초자료연구)

  • 김종춘;이상준;배진숙;박종일;김용범;정문구
    • Toxicological Research
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    • v.17 no.2
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    • pp.83-90
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    • 2001
  • The background control data were compiled from rat developmental toxicity studies con-ducted at Toxicology Research Center, KRICT during the 1993-1999 period. These data were assembled in order to provide background in formation for the maternal and fetal data collected in 13 developmental toxicity studies using Sprague-Dawley rats. A total of 325 mated females were used in these studies during the seven-year period and overall pregnancy rate of these females was 93.8%. The present background control data included body weights, food consumption, hematological values, and organ weights of pregnant females, caesarean section data, and fetal examination data. These data can be used not only as a historical database for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization oj Sprague-Dawley rats.

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Effects of Korean Red Ginseng Water Extract on Bisphenol A-induced Developmental Toxicity in Rats (랫드에서 비스페놀 A의 발생독성에 대한 고려홍삼 물추출물의 효과)

  • 김종춘;임광현;서정은;위재준;남기열;정문구
    • Toxicological Research
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    • v.17 no.3
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    • pp.225-234
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    • 2001
  • The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

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Effects of 00 Hz Horizontally Polarized Magnetic Fields on Embryo-fetal Development in SD Rats (SD 랫드의 배 .태자발생에 대한 60 Hz 수평자계의 영향)

  • 정문구;김종춘;명성호;김상범;이동일
    • Toxicological Research
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    • v.17 no.4
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    • pp.279-286
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    • 2001
  • Recently, there is an increasing nationwide concern in Korea that exposure to electric and magnetic fields in the home environment may not be safe in humans. To identify possible effects of horizontally polarized magnetic fields (MF) exposure on embryo-fetal development, timed-mated female Sprague-Dawley rats (24/group) received continuous exposure to 60 Hz MF at field strengths of 0 Gauss (sham control), 50mG,833 mG, or 5000 mG. Dams received MF of sham exposures for 22hr/day on gestation days 6 through 20. Experimentally generated MF were monitored continuously througout the study. There was no evidence of maternal toxicity of developmental toxicity in any MF-exposed groups. Mean maternal body weight, organ weights, and gross findings in groups exposed to MF did not differ from those in sham control. No significant differences in fetal deaths, fetal body weight, and placental weight were observed between MF-exposed groups and sham control. External, visceral, and skeletal examination of fetuses demonstrated no significant differences in the incidence of fetal malformations between MF-exposed and sham control groups. In conclusion, exposure of pregnant Sprague-Dawley rats to 60 Hz at MF strengths up to 5000 mG during gestation day 6-20 did not produce any biologically significant effect in either dams of fetuses.

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Reproductive Toxicity Study of Aspalatone, A New Antithrombetic Agent: Teratogenicity Study in Rats (항혈전제 아스파라톤의 생식독성연구:랫드 최기헝성시험)

  • 정문구;이상준;김종춘;송시환
    • 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.

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Assessment of Embryotoxicity of 2-Bromopropane in ICR Mice

  • Kim, Jong-Choon;Shin, Dong-Ho;Kim, Sung-Ho;Oh, Ki-Seok;Kim, Hyeon-Yeong;Her, Jeong-Doo;Jiang, Cheng-Zhe;Chung, Moon-Koo
    • Toxicological Research
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    • v.19 no.3
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    • pp.227-234
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    • 2003
  • 2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. 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 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 313, 625 or 1,250 mg/kg/day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1,250 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs and a decrease in the maternal body weight, body weight gain, and corrected body weight. Developmental toxicity included a decrease in the fetal body weight, a reduction in the placental weight, an increase in the fetal skeletal variation and ossification delay. There were no adverse effects on either pregnant dams or embryo-fetal development in the 313 and 625 mg/kg groups. These results suggest that a 12-day subcutaneous dose of 2-BP is embryotoxic at a maternally toxic dose (i.e., 1,250 mg/kg/day) in ICR mice. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 625 mg/kg/day for dams and embryo-fetuses, respectively.

Development Toxicity Evaluation (랫드에서 표준 및 사료제한 시험에 의한 fluoroquinolone 항균제 DW-116의 발생독성평가)

  • 김종춘;윤효인;이희복;한상섭;정문구
    • Journal of Life Science
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    • v.11 no.5
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    • pp.447-456
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    • 2001
  • We have recently demonstrated that the fluoroquinolone antibacterial DW-116 caused a significant developmental toxicity in rats. The present study was conducted to determine whether the development toxicity induced by DW-116 treatment was the result of malnutrition fro reduced food intake or the direct effects of test chemical on conceptuses. The test chemical was administered by gavage to pregnant rats from gestational days 6 through 16 at dose levels of 0 and 500 mg/kg/day. A pair-feeding study was also performed in which the pregnant rats received the same amount of diet consumed by the DW-116-treated pregnant rats. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for examined for external, visceral, and skeletal abnormalities. In this treatment group, the maternal toxicities included increased abnormal clinical signs, decreased maternal body weight, suppressed body weight gain during treatment and posttreatment periods, and reduced food intake. The significant developmental toxicities included increased fetal deaths, decreased live fetuses, reduced fetal body weight and placental weight, increased incidence of fetal abnormalities, and increased fetal ossification delay. In this pair-fed group, however, slight maternal toxicities including decreased body weight and suppressed body weight gain during treatment period were observed in comparison with the control group, and minimal development toxicities including reduced fetal and placental weights and increased fetal ossification delay were found. The number of fetal deaths and live fetuses, and the incidences of malformed fetuses and litters with affected fetuses were comparable to the control values. Based on the results, it could be concluded that the development toxicity observed in the treatment group is attributable to the direct effects of Dw-116 treatment, but not to the maternal malnutrition from reduced food consumption during pregnancy.

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

  • Kim, Jong-Choon;Oh, Ki-Seok;Shin, Dong-Ho;Kim, Sung-Ho;Kim, Hyeon-Yeong;Yun, Hyo-In;Jiang, Cheng-Zhe;Heo, Jeong-Doo;Chung, Moon-Koo
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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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.

Embryo-Fetal Development Study of 2-Bromopropane in Rats

  • Jiang, Cheng-Zhe;Jeung, Na-Young;Chung, Moon-Koo
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.203-203
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    • 2002
  • The present study was conducted to investigate the potential embryo-fetal toxicity of 2-bromopropane(2-BP) in rats. The test agent was subcutaneously administered to pregnant rats from gestational day 6 to 19 at dose level of 0, 500, 1000, 1500 mg/kg.(omitted)

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