• Toxicological Research
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• v.23 no.2
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• pp.151-158
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• 2007

tert-Butyl acetate is an organic solvent used for coatings, industrial cleaning, and surface treatment applications. This study investigated the potential adverse effects of tert-butyl acetate on pregnant dams and embryo-fetal development after maternal exposure on gestational days 6 through 19 in rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 500, 1,000, 1,500, and 2,000 mg/kg/day. All dams were subjected to a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 2,000 mg/kg, treatment-related clinical signs, including piloerection, abnormal gait, decreased locomotor activity, loss of fur, reddish tear, anorexia, nasal discharge, vocalization and coma, were observed in a dose-dependent manner. All dams died between the 2nd day and 5th day of treatment due to a severe systemic toxicity. At 1,500 mg/kg, minimal maternal toxicity including an increase in the incidence of decreased locomotor activity and loss of fur, and an increase in the weights of adrenal glands and liver was observed. On the contrary, no significant adverse effect on the embryo-fetal development was detected. There were no adverse effects on either pregnant dams or embryo-fetal development at <1,000 mg/kg. These results show that a 14-day repeated oral dose of tert-butyl acetate in rats caused a minimal maternal toxicity including increases in the incidence of clinical signs and the weights of adrenal glands and liver, but no embryotoxicity and teratogenicity at 1,500 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of tert-butyl acetate is estimated to be 1,000 mg/kg per day for dams and 1,500 mg/kg per day for embryo-fetal development.

• Toxicological Research
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• v.24 no.4
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.113-117
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• 2001

The screening of various molecular descriptors for predicting carcinogenic, mutagenic and teratogenic activities of chlorinated aliphatic compounds as drinking water disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The present work embodies the study of relationship between molecular descriptors and toxicity parameters of the genotoxicity endpoints for the screening of relevant molecular descriptors. The toxicity Indices for 29 compounds constituting the testing set were computed by the PASS program and active values were chosen. We investigate feasibility of screening descriptors and of their applications among different genotoxic endpoints. The correlation to teratogenicity of all 29 compounds was significantly improved when the same analysis was done with 20 alkanes only without alkene compounds. The HOMO (highest occupied molecular orbital) energy and number of Cl parameters were dominantly contributed.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.149-155
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• 1996

Doctors who treat pregnant women ore usually cautious in writing their prescription for the drugs. The problem of which psychotropic medications ore sale during pregnancy seems to remain unsolved for many years. Although the rate of absorption is reduced due to a reduced rate of gastric emptying, the extent of absorption of drug is generally unchanged during pregnancy. Plasma volume and total body water increase during pregnancy. There is suggestion that drug metabolizing activity may be increased in pregnancy. Since the pregnancy increase the glomerular filtration rate significantly, drugs mainly eliminated by renal excretion will be cleared more quickly. Factors contributing to the potential teratogenecity of a drug include the type of compound, dose and duration of use, developmental stage of fetus at the time of exposure, and the effect of the drug on fetal pharmacokinetics. All major classes of psychotropic agents should be assumed to diffuse readily across the placenta to the fetus and to be present in some quantity in the breast milk. To decide when and how to start the drug treatment depends on an assessment of the risks related both with and without drug treatment of psychiatric disorders.

• Toxicological Research
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• v.11 no.1
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• pp.37-42
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• 1995

Effect of cadmium on the early amphibian development was analyzed through FETAX (Frog Embryo Teratogenesis Assay: Xenopus). Embryos manifested concentration-dependent mortality and realformations; shortage of anterior-posterior axis gut realformation, ocular anomalies, bent notochord, misshapen dorsal fin, and derreal blisters. The treatment with 1.5ppm cadmium solution caused 100% mortality and concentration of lppm did not kill the embryos that caused 100% anomaly. The teratogenic index (TI = LC50 /EC50) was 2.8 indicating that $CdCl_2$ is teratogenic for Xenopus laevis. Embryos that were pulsetreated with at early to late blastula stage (St. 3-9) and mid to late blastula stage (St. 6-10) showed relatively strong resistance to cadmium, but the embryos treated at gastrula stage (St. 10-13) showed high mortality. And the embryos treated at tailbud stage (after St. 25) showed highest mortality of any other early stages. Effects of temperature were studied through pulse- treatment during gastrula stage at $20^{\circ}C$ and $30^{\circ}C$. The embryos treated with 7.5ppm at $30^{\circ}C$ and 15ppm at $20^{\circ}C$ caused 100% mortality respectively, indicating that higher temperature had more severe toxic effect. One of the most peculiar effect of cadmium at gastrulation was distortion of the tail. The probable cause of toxic effect of Cd was discussed.

• Toxicological Research
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• v.3 no.1
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• pp.45-53
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• 1987

A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.68-72
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• 2014

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with $K_m$ of $168{\mu}M$ and $371{\mu}M$ in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [$^3H$]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [$^3H$]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.

• 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.

• 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.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.821-831
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• 1994

Phenytoin(PHT), a commonly prescribed anticonvulsant, has been known as a teratogen in experimental animals and human. However, PHT has strain-specific teratogenic effects for mice and human. Dimethyl sulfoxids(DMSO) has been known to antagonize the teratogenic effects of secalonic acid D, a toxic mold metabolite that has similar teratogenic effects to PHT. Therefore, this study was performed to examine the embryopathic effects of PHT in terms of treatment period and the antiteratogenic effect of DMSO in ICR mice. PHT(75mg/kg, BW) was administered intrapetitoneally on day 10, 10-11 and 10-12 of gestation with or without DMSO(2ml/kg, BW), and the fetal malformation was observed on day 18. Major malformation of fetuses treated with PHT on day 10, 10-11 and 10-12 of gestation was cleft palate, and the percentages of fetus with cleft palate were 14.5%, 31.7% and 51.7%, respectively. Also, there was a significant decrease of cleft palate from 51.7% in PHT alone group to 30.8% in PHT plus DMSO group. Our findings suggest that cleft palate is one of major malformation by PHT treatment in ICR mouse and DMSO has strong antiteratogenic effect.