• 제목/요약/키워드: Fetal toxicity

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

  • 정명현;유선용
    • 한국정보통신학회:학술대회논문집
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    • 한국정보통신학회 2022년도 춘계학술대회
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    • pp.273-275
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    • 2022
  • 임산부에게 약물을 사용하는 것은 태아에게 잠재적인 위협이 될 수 있으므로 임산부가 복용을 피해야 할 약물을 분류하는 것은 필수적이다. 하지만 많은 화합물이 태아에게 독성을 나타낼 수 있는지에 대한 근거가 불분명하며, 그것을 밝혀내기 위해서는 많은 시간과 비용이 투자된다. In silico 기반 가상 스크리닝은 광범위한 화합물에 대해서 적은 비용과 시간으로 어떤 화합물이 태아에게 높은 위험을 보일 수 있는지 예측하는데 활용될 수 있다. 우리는 한국과 호주 정부의 임신 중 약물 처방을 위한 위험 분류 리스트를 활용해 약물의 분류 등급 정보를 가져왔다. 약물의 구조적 특징과 화학적 특징을 기반으로 다양한 머신 러닝 기법을 적용하여 약물의 태아 독성 여부를 예측하는 모델을 생성하였으며, 정량적 성능 평가를 수행하였다. 나아가, attention 알고리즘을 활용하여 제안하는 모델이 약물의 태아 독성을 예측하는 과정에서 화합물의 어떤 하위 분자 구조가 중요하게 활용되었는지 확인하였다. 해당 연구를 통해 광범위한 화합물에 대해 높은 태아 독성 위험도를 가진 약물을 머신 러닝을 통해 예측할 수 있는 것을 확인하였다. 우리의 연구는 단순한 약물의 태아 독성 예측에서 나아가, 유의미한 하위 분자구조를 제공함으로써 연구자들이 약물의 태아 독성을 증명하기 위해 수행하는 실험에서 핵심적인 역할이 가능할 것이다.

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

  • 김종춘;이상준;배진숙;박종일;김용범;정문구
    • Toxicological Research
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    • 제17권2호
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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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랫드에서 비스페놀 A의 발생독성에 대한 고려홍삼 물추출물의 효과 (Effects of Korean Red Ginseng Water Extract on Bisphenol A-induced Developmental Toxicity in Rats)

  • 김종춘;임광현;서정은;위재준;남기열;정문구
    • Toxicological Research
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    • 제17권3호
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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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SD 랫드의 배 .태자발생에 대한 60 Hz 수평자계의 영향 (Effects of 00 Hz Horizontally Polarized Magnetic Fields on Embryo-fetal Development in SD Rats)

  • 정문구;김종춘;명성호;김상범;이동일
    • Toxicological Research
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    • 제17권4호
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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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항혈전제 아스파라톤의 생식독성연구:랫드 최기헝성시험 (Reproductive Toxicity Study of Aspalatone, A New Antithrombetic Agent: Teratogenicity Study in Rats)

  • 정문구;이상준;김종춘;송시환
    • Biomolecules & Therapeutics
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    • 제6권2호
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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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    • 제19권3호
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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.

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

  • 김종춘;윤효인;이희복;한상섭;정문구
    • 생명과학회지
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    • 제11권5호
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    • pp.447-456
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    • 2001
  • 임신랫드에서 fluoroquinolone 항균제 DW-116에 의해 유발된 발생독성이 모동물의 사료섭취량 감소에 의한 영양 결핍이 주요 원인인지 아니면 DW-116이 배.태자에 직접적으로 작용하여 유발된것인지를 조사하고자 시험물질을 랫드에 임신 6일에서 16일까지 0 및 500 mg/kg 용량으로 반복 경구투여하였다. 사료제한군은 시험물질 투여군의 모동물의 섭취한 동일한 양의 사료를 제한급여하였다. 모든모동물을 임신 20일째에 제왕절개하였고, 모독성 및 발생독성을 평가하였다. 시험물질 투여군에서는 독성증상과 체중의 감소, 투여 및 투여후 기간의 체중증가 억제, 사료섭취량의 감소를 포함하는 모독성이 부형제대조군및 사료제한군에 비해 현저하게 증가하였다. 또한, 태자사망의 증가, 생존태자의 감소, 태자체중과 태반중량의 감소, 태자기형의 증가 및 골환지연을 포함하는 발생독성도 현저하게 증가하였다. 반면, 사료제한군에서는 모체 및 태자에서 경미한 독성고견만 인정되었고, 태자사망이나 태자기형 등의 심각한 발생독성은 관찰되지 않았다. 결론적으로 시험물질투여군에서 관찰된 발생독성은 사료섭취량의 감소에 의한 모체의 영양결핍에 기인된 것이 아니라 DW-116의 투여에 기인된 직접효과인 것으로 판단된다.

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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.

Embryo-Fetal Development Study of 2-Bromopropane in Rats

  • Jiang, Cheng-Zhe;Jeung, Na-Young;Chung, Moon-Koo
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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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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