• Toxicological Research
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• v.19 no.1
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• pp.21-27
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• 2003

A teratogenic study of dimethyl dimethoxy biphenylate derivative (DDB-S) was carried out on Sprague-Dawley rats. DDB-S dissolved in saline was administered to male and female rats by intravenously injection at daily doses of 50 mg/kg, 75 mg/kg, and 100 mg/kg. A half 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 necropsy findings of dams. No gross, skeletal and visceral abnormalities was observed in F1 fetuses from dams treated with DDB-S. F1 offsprings did not show any treatment-related difference in growth, reflex, behaviour and reproductive performance. At caesarean section of F1 dams, no growth retardation and gross abnormality was observed in F2 fetuses. In conclusion, DDB-S did not show any potential teratogenic effect in rats.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.691-700
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• 2008

One suggested mechanism underlying copper (Cu) deficiency teratogenicity is a low availability of nitric oxide (NO), signaling molecule which is essential in developmental processes. Increased superoxide anions secondary to decreased activities of Cu-zinc superoxide dismutase (Cu-Zn SOD) in Cu deficiency can interact with NO to form peroxynitrite, which can nitrate proteins at tyrosine residues. In addition, peroxynitrite formation can limit NO bioavailability. We previously reported low NO availability and increased protein nitration in Cu deficient (Cu-) embryos. In the current study, we tested whether Cu deficiency alters downstream signaling of NO by assessing cyclic GMP (cGMP) and phosphorylated vasodilator-stimulating phosphoprotein (VASP) levels, and whether NO supplementation can affect these targets as well as protein nitration. Gestation day 8.5 embryos from Cu adequate (Cu+) or Cu- dams were collected and cultured in either Cu+ or Cu- media for 48 hr. A subset of embryos was cultured in Cu- media supplemented with a NO donor (DETA/NONOate; 20 ${\mu}M$) and/or Cu-Zn SOD. Cu-/Cu- embryos showed a higher incidence of embryonic and yolk sac abnormalities, low NO availability, blunted dose-response in NO concentrations to increasing doses of acetylcholine, low mRNA expression of endothelial nitric oxide synthase (eNOS), increased levels of 3-nitrotyrosine (3-NT) compared to Cu+/Cu+ controls. cGMP concentrations tended to be low in Cu-/Cu- embryos, and they were significantly lower in Cu-/Cu- yolk sacs than in controls. Levels of phosphorylated VASP at serine 239 (P-VASP) were similar in all groups. NO donor supplementation to the Cu- media ameliorated embryonic and yolk sac abnormalities, and resulted in increased levels of cGMP without altering levels of P-VASP and 3-NT. Taken together, these data support the concept that Cu deficiency limits NO availability and alters NO/cGMP-dependent signaling in Cu- embryos and yolk sacs, which contributes to Cu deficiency-induced abnormal development.

• 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.

• Korean Journal of Environmental Biology
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• v.39 no.3
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• pp.311-318
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• 2021

In this experiment, we investigated the toxicity of tebuconazole (fungicide) using domestic frog embryos, along the FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol. Bufo gargarizans, Hyla japonica, and Pelophylax nigromaculatus embryos were incubated, and investigation of the tebuconazole effect was performed by the probit analysis. As a result, depending on the concentrations of tebuconazole, the mortality and malformation rates were increased and larval body length was decreased. The teratogenic concentrations (EC₅₀) of tebuconazole were 34.4mg L^-1, 10.6mg L^-1, and 14.9mg L^-1, respectively, and the embryo lethal concentrations(LC₅₀) of tebuconazole were 74.7 mg L^-1, 38.5 mg L^-1, and 39.1 mg L^-1, respectively. The teratogenic index (TI) valuesof tebuconazole were 2.19, 3.58, and 2.65; thus, it showed teratogenicity in embryonic development of these three frogs. These results revealed that in this experiment, tebuconazole suppressed the development of embryos at a relatively low concentration. In addition, mortality, malformation ratios, malformation patterns, and growth rates were similar to the results from the other assay systems. Therefore, tebuconazole was thought to have an effect on the embryo development of domestic frogs. In future, it will be necessary to identify species specificity in order to the clarify the causes of differences in mortality, malformation rate, and malformation patterns depending on the species.

• Journal of Life Science
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• v.33 no.6
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• pp.490-497
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• 2023

Pregnant women may need to take medications to treat preexisting diseases or diseases that develop during pregnancy. However, some drugs may be fetotoxic and lead to, for example, teratogenicity and growth retardation. Predicting the fetotoxicity of drugs is thus important for the health of the mother and fetus. The fetotoxicity of many drugs has not been established because various challenges hinder the ability of researchers to determine their fetotoxicity. The need exists for in silico-based fetotoxicity assessment models, as they can modernize the testing paradigm, improve predictability, and reduce the use of animals and the costs of fetotoxicity testing. In this study, we collected data on the fetotoxicity of drugs and constructed fetotoxicity prediction models based on various machine learning algorithms. We optimized the models for more precise predictions by tuning the hyperparameters. We then performed quantitative performance evaluations. The results indicated that the constructed machine learning-based models had high performance (AUROC >0.85, AUPR >0.9) in fetotoxicity prediction. We also analyzed the feature importance of our model's predictions, which could be leveraged to identify the specific features of drugs that are strongly associated with fetotoxicity. The proposed model can be used to prescreen drugs and drug candidates at a lower cost and in less time. It provides a predictive score for fetotoxicity risk, which may be beneficial in the design of studies on fetotoxicity in human pregnancy.

• Korean Journal of Ecology and Environment
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• v.36 no.1 s.102
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• pp.83-94
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• 2003

Concentrated releases of zinc into water usually results from discharges associated with industrial purpose. The released zinc into soil is corroded and released into water. In aquatic environment, exess zinc is toxic to the organisms and causes the growth inhibition and malformation of them as a heavy metal. In this study, excess zinc toxicity was tested by FETAX (frog embryo teratogenetic assay with Xenopus)as in vivo system. Xenopus embryos at st.9 were exposed to $100{\sim}900\;{\mu}M$ of zinc for 7 days and 81% of individuals were survived in 100 ${\mu}M$, and 25% were survived in 1000M of zinc solution. In external malformations, swelled belly and intestinal dysplasia were common, and all of tested individuals showed these malformations in 200 ${\mu}M$ or higher concentration of zinc. In 400 ${\mu}M$ or higher concentration, all of tested tadpoles showed faded heart. Also, hypo-pigmentation, lens hernia and loose digestive track were very frequently found in 100 ${\mu}M$ of zinc. The histological study with paraffin section of zinc treated tadpoles showed following abnormalities; regeneration of photoreceptor on retina, reduced vitreous chamber in eye, reduction of red blood cells in heart, abnormal liver, swelling of pronephric cell, muscle dysplasia and palatal papilloma. These abnormalities may be caused by the degeneration of mitochondria, inhibition of cell adhesion, and the formation of leghemoglobin by zinc due to the substitution of $Ca^{2+}$ by $Zn^{2+}$. The body length was reduced due to the excess zinc. From a statistical result, body lengths of 300 ${\mu}M$ or higher concentrative g개ups was significantly reduced comparing that of control group. Recently, many spontaneous malformations and reduction of amphibians are reported, From the results of present study, excess zinc mi호t be a factor of amphibian reduction, and the control of zinc discharges is very important.

• Korean Journal of Biological Psychiatry
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• v.14 no.2
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• pp.91-98
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• 2007

Objectives : Considering the impact of depressive illness on physical and mental health of both mother and fetus, specification of a treatment algorithm for depressive disorder during pregnancy is legitimated. This article provides a systemic review of treatments for depressive disorder during pregnancy and lactation. Methods : According to the search strategy of the Clinical Research Center for Depression of Korean Health 21 R & D Project, PubMed and EMBASE were searched using terms with regard to the treatment of depressive disorders during pregnancy and lactation. Reference lists of related reviews and studies were searched. In addition, relevant practice guidelines were searched using the PubMed. All identified clinical literatures were reviewed and summarized in a narrative manner. Results : Pharmacotherapy during pregnancy and lactation requires a comprehensive assessment of the risks and benefits of treatment for both mother and fetus or neonate. Recently, there is growing evidence that the use of tricyclic and selective serotonin reuptake inhibitors during pregnancy and lactation does not result in increased risks of teratogenicity. Treatment strategies are described according to the point of time of pregnancy or lactation. FDA categories for antidepressants during pregnancy and lactation are described. In addition, issues regarding to the electroconvulsive therapy and psychosocial treatment are discussed. Conclusion : The treatment option for depressive disorders during pregnancy and lactation depends on the severity of depressive illnesses of the individual patient. For mild to moderate depression, the non-pharmacological treatment should be considered first. For moderate to severe depression, pharmacotherapy should be administered in addition to the psychosocial treatment. ECT is recommended for depressive disorder of severe intensity. As the research knowledge is limited, the recommendations should based on the best judgement of psychiatrists.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.2
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• pp.111-118
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• 2016

Acne vulgaris is a chronic inflammatory condition characterized by comedo, papule, cyst, nodule and postinflammatory hyperpigmentation. Meanwhile, it is also induced by adverse event of drugs. Among them, acneiform folliculitis is a side effect of epidermal growth factor receptor (EGFR) inhibitor, which is an anticancer agent, and its incidence may occur in upward of 75 ~ 100% of cases. The main method of acne vulgaris treatment is oral antibiotics, retinoids, topical medication and so on. However, it is limitation that teratogenicity caused by retinoids and antibiotic resistance increased by using antibiotics. In this study, we aimed to evaluate the clinical efficacy and safety of topical recombinant human (rh) EGF in treating facial acne vulgaris. Twenty three Koreans (age: 10 ~ 29 years) with mild to moderate acne vulgar participated in the study and applied topical rhEGF cream (trouble control EGF) with 3 products (trouble control clarifying cleansing foam, trouble control all-clear filling toner, redroll calming moisture) on their face twice daily for four weeks. Several assessment methods were applied: Acne lesion counts score by investigator's global assessment, efficacy and satisfaction score by subjects. Skin sebum output level, hydration level and redness level were also measured at each visit. At the final visit, skin sebum level, transepidermal water loss, skin redness statistically decreased and acne lesions (comedone, papule) were statistically reduced. No severe side effects were observed during the study. In conclusion, topical rhEGF seems to be an effective and safe adjuvant treatment option for mild acne vulgaris.