• Toxicological Research
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• v.7 no.2
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• pp.257-265
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• 1991

실험동물을 이용한 생식독성시험 결과를 기초로 하여 화학물질의 인체내 최기형성 발현 잠재력을 추정하는 질적인 독성평가는 비교적 용이하다. 그러나 인체에 실제로 적용할 수 있는 생식 독성 평가를 위해서는 양적인 독성평가가 요구되는데 여러가지 기본원칙의 불일치성과 검색기술등의 부조으로 아직 학문적인 평가가 어려운 실정이다. 따라서 본 seminar에서는 양적인 독성 평가의 어려운 문제점에 대한 세계적 연구추세를 소개하는 일례로서, 독일 베를린 자유대 독성학 연구소에서 다년간 수행된, 약제의 동물실험결과를 토대로 최기형 효과에 대한 평가시 고려해야 할 제반요소와 원칙에 대해 다음과 같이 소개하고자 한다.

• Korean Journal of Environment and Ecology
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• v.18 no.3
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• pp.340-345
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• 2004

The embryotoxic effects of PCB (Aroclor 1248) on a Korean frog, Rana dybowskii was deter-mined by using the FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol. The rates of mortality and malformed larvae were investigated by probit analysis. The results showed that PCB is highly embryolethal. From LC$_{50}$ of 1.48ppb and from EC$_{50}$ of 0.25ppb and TI of 5.7 were derived, which indicates PCB is to be considered a teratogenic compound. Specific malformations occurred in 62.0% as edema at the 0.1ppb, in 32.0% as tail deformations at the 1ppb, and in 68.0% as profound deformations at the 5ppb of PCB concentration which living embryos were exposed to. PCB suppressed the growth of head-tail length at a relatively low concentration (1.0ppb), and therefore growth inhibition as assessed by embryo length can be used as a sensitive indicator to evaluate the toxicity of pollutants in the environment. In conclusion, PCB must be considered highly embryotoxic to Rana dybowskii.

• Korean Journal of Environment and Ecology
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• v.33 no.2
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• pp.178-186
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• 2019

This study used the probit analysis to evaluate the toxicity of three chemicals - benomyl (Germicide), carbofuran (insecticide), and thiobencarb (herbicide) - with the FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol using the incubated embryos of tree frog, Hyla japonica. The results showed that the larval body length decreased while the mortality and malformation rates increased as the concentrations of benomyl, carbofuran, and thiobencarb increased. The teratogenic concentration ($EC_{50}$) of benomyl, carbofuran, and thiobencarb were 1.00, 0.58, 4.75 mg/L, respectively, indicating that the malformation of larvae was the most sensitive to carbofuran. The embryo lethal concentration ($LC_{50}$) was 7.04, 28.71, and 16.12mg/L, respectively, indicating that benomyl showed the lowest embryo lethal concentration. The teratogenic index (TI) was 7.04 in Benomyl, 49.50 in Carbofuran, and 3.39 in Thiobencarb, indicating that the TI values were above 1.5, which is the criterion of teratogenicity, for all three chemicals. All three pesticides examined by this study were considered to be the most teratogenic substances, and the carbofuran was the most potent teratogen.

• Korean Journal of Environment and Ecology
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• v.30 no.4
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• pp.705-711
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• 2016

In this experiment, embryos of Asian toad, Bufo gargarizans, were investigated to evaluate toxicity of chemicals along FETAX(Frog Embryo Teratogenesis Assay-Xenopus) protocol. Asian toad, Bufo gargarizans, embryos incubated and investigation of Zn and Benomyl effect by probit analysis. As a result, depends on the concentrations of Zn and Benomyl, mortality and malformation rates were increases and larval body length were decreased. The teratogenic concentration($EC_{50}$) of Zn and Benomyl were 2.3, $1.0mg/{\ell}$, respectively and the embryo lethal concentration($LC_{50}$) Zn and Benomyl were 10.3, 6.9, respectively. The teratogenic index(TI) were 4.4 in Zn and 6.7 in Benomyl, thus showed teratogenicity in embryonic development of B. gargarizans. These results reveal that Zn and Benomyl in this experiment suppressed the development of embryos at relatively low concentration. Much of B. gargarizans embryos can be secured, and easy to incubate. In addition, mortality, malformation ratios, malformation patterns and growth rates are similar to the results from the other assay systems. Therefore, the B. gargarizans embryo teratogenesis assay system could be a useful tool to evaluate toxicity of pollutants in environment.

• Journal of Korean Neurosurgical Society
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• v.29 no.4
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• pp.500-506
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• 2000

Objective : To determine the role of preoperative embolization on postoperative neurological outcome in the treatment of cerebral AVMs, we retrospectively evaluated an effectiveness of combining preoperative embolization and microsurgery for arteriovenous malformations(AVM) of the brain. Method : Two groups(10 patients who underwent preoperative superselective embolization and surgery versus 27 patients who underwent surgery only) were compared and categorized by Spetzler-Martin grade, the size of AVM and postoperative clinical outcome using Glasgow Outcome Scale. The 37 patients included 23 males and 14 females, ranging in age from 11 to 74 years(mean 36 years). Results : The arteriovenous malformations in preoperative embolization and surgery group had a larger average greatest diameter(4.45cm versus 3.83cm) and were of higher Spetzler-Martin grade(80% versus 52% grade III through V). At 1 week after surgery, the preoperative embolization and surgery group represented a better outcome(60% versus 44% with Glasgow Outcome Scale score of 5). And over 6 months after surgery, the embolization and surgery group displayed more favorable clinical outcome(80% versus 63% with Glasgow Outcome Scale score of 5). Conclusion : Combined treatment with superselective preoperative embolization using N-butyl cyanoacrylate and direct surgery may help neurosurgeon treating the high grade AVMs thus improving the postsurgical outcome.

• Korean Journal of Environment and Ecology
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• v.26 no.5
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• pp.675-681
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• 2012

In this experiment, I investigated toxicity evaluation of chemicals using domestic frog embryos, along FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol. I investigated $Cu^{2+}$ and Tebuconazole effect on the tree frog, Hyla japonica, embryos by probit analysis. Mortality and malformation rates increased and larval body length decreased depending on the concentrations of $Cu^{2+}$ and Tebuconazole. The teratogenic concentration ($EC_{50}$) of $Cu^{2+}$ and Tebuconazole were 0.05, 5.0mg/${\ell}$, respectively and the embryo lethal concentration ($LC_{50}$) of $Cu^{2+}$ and Tebuconazole were 0.16, 38.5, respectively. The teratogenic index (TI) appeared 3.0 in $Cu^{2+}$ and 7.7 in Tebuconazole, which showed teratogenicity in embryonic development of Hyla japonica. These results reveal that $Cu^{2+}$ and Tebuconazole in this experiment suppressed the development of embryos at relatively low concentration. Much of Hyla japonica embryos can be secured, and easy to incubate. In addition, mortality, malformation ratios, malformation patterns and growth rates are similar to the results from the other assay systems. Therefore, the Hyla japonica embryo teratogenesis assay system could be a useful tool to evaluate toxicity of pollutants in environment.

• Korean Journal of Environmental Biology
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• v.30 no.3
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• pp.231-237
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• 2012

Toxicity of $Ni^{2+}$ and Tebuconazole were investigated via FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol using domestic frog embryos. Embryos of Black-spotted pond frog, Rana nigromaculata, were incubated and toxic effects of $Ni^{2+}$ and Tebuconazole were investigated by probit analysis. As a result, mortality and malformation rates were increased and larval body length was decreased in a dose dependant manner of $Ni^{2+}$ and Tebuconazole. The half maximal effective concentration ($EC_{50}$) of $Ni^{2+}$ and Tebuconazole were 0.07, $12.7mg\;L^{-1}$, respectively and the half maximal lethal concentration ($LC_{50}$) of $Ni^{2+}$ and Tebuconazole were 4.2, 39.1, respectively. The teratogenic index (TI) were 61.4 in $Ni^{2+}$ and 3.1 in Tebuconazole, respectively. These results reveals that $Ni^{2+}$ and Tebuconazole suppress the development of Black-spotted pond frog embryos at the low concentration as showing teratogenic effects in other assay system. Therefore, teratogen assay system using the Rana nigromaculata embryos could be useful as a tool to evaluate the toxicity of the pollutants in environment.

• Korean Journal of Veterinary Research
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• v.34 no.1
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• pp.69-75
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• 1994

Pregnant CD-1 mice were exposed to methylmercury in the drinking water at concentration of 20ppm with subcutaneous treatment of thiaminHCl(vitamin $B_1$) (100mg, 200mg or 300mg/ kg b.w.) or BAL(5.0 mg/kg b.w.) under the alone or combined base at the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters, including body weight and crown-rump length in the mice exposed to mercury, were reduced as placental weight compared to those in the control group(no treatment). The incidence of dead fetuses/resorption and malformed fetuses(especially cleft palate) was also increased even in the group treated with thrapeutic agents as well as in the mercury only treated group. However, all kinds of alteration indicated above, possibly induced by mercury, reduced/or decreased significantly compared to those of control. A subtle indication of maternal toxicity was noted in most experimental animals as evidenced by decreased water consumption and increased relative liver weight. The present study confirmed that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when administered during organogenesis and that thiamin administration may have therapeutic application for the treatment or prevention against of deleterious effects induced by mercury during gestation period.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.361-368
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• 1994

Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.121-128
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• 1998

Ochratoxin A (OA) is a mycotoxin produced by Aspergillus ochraceus as well as other molds. It is a natural contaminant of mouldy food and feed. OA has a number of toxic effects, the most prominant being nephrotoxicity. Futhermore, OA is immunosuppressive, genotoxic, teratogenic and carcinogenic. OA inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently, lipid peroxidation induced by OA has been reported, indicating that the lesion induced by this mycotoxin could be also related to oxidative pathway. Since it seems impossible to avoid contamination of foodstuffs by toxigenic fungi, detoxification and detoxication of OA are needed. In this study we investigated the protective effects of aspartame (Asp), phenylalanine (Phe), polyphenol 70S (PP) and aloe extract (AE) on the nephrotoxicity induced by subacute exposure to the OA. Asp and Phe are structural analogues of OA. PP, an ingredient of Green Tea and AE have been known as antioxidant and radical scavenger. Phe (40 mg/kg, i.p.) and Asp (25 mg/kg, p.o.) were administered to Sprague-Dawley rats simultaneously with OA (2.0 mg/kg, p.o.) for 2 weeks. PP (200 mg/kg, p.o.) and AE (50 mg/kg, i.v.) were pretreated before administration of OA, for 2 weeks and 3 days, respectively. Using enzymuria, BUN level, creatinemia and histophathologic examination as indices of renal damage, we observed that all of four compounds prevented the nephrotoxic effects induced by OA. It seems that structural analogues of OA such as Asp and Phe have better protective effect on the nephrotoxicity of OA than antioxidants. These results indicate that 1) formation of free radical and lipid peroxidation are likely to be involved in the nephrotoxicity of OA in vivo, 2) Asp, PP and AE might be used for prevention of renal lesions in cases of ochratoxicosis.