• Toxicological Research
• /
• 제11권1호
• /
• pp.81-89
• /
• 1995

A teratogenicity study of KTC-1, a new semisynthetic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 7, 21, and 63 mg/kg/day were administered to darns orally gayage from day 7 to day 17 of gestation. Two-third of dams per group were subjected to cesarean section on day 21 of pregnancy for examination of their fetuses, and the remaining one-third of darns per group were allowed to deliver naturally for postnatal examination of their offspring. At 21 mg/kg/day, an increase in the skeletal variations of F1 fetuses and a decrease in the body weight of F1 offspring were seen. At 63 mg/kg/day, a loss in body weight was observed in darns. An increase in fetal death rate, a decrease in litter size and body weight, and an increase in the incidence of visceral malforrnations and skeletal variations were found in F1 fetuses. In particular, lumar rib occurred at an incidence of 31%. In addition, an increase in the dead newborns at birth and neonatal deaths during the lactation period, a loss in body weight, and a decrease in spleen weight were observed in F1 offspring. There were no signs of maternal toxicity or embryotoxicity at 7 mg/kg/day. The results suggest that the no-effect dose level(NOEL)for dams is 21 mg/kg/day, and NOELs for F1 fetuses and offspring are 7 mg/kg/day.

• Biomolecules & Therapeutics
• /
• 제9권4호
• /
• pp.311-317
• /
• 2001

YHB6211, a newly developed recombinant human granulocyte colonystimulating factor, was administered at dose levels of 0, 3, 15, and 75 $\mu$g/kg/day intravenously to the pregnant New Zealand White rabbits (20 rabbits per group) during the organogenetic period, days 6 to 18 of gestation. All dams were subjected to Caesarian section on day 28 of gestation and their fetuses were examined for external, visceral, and skeletal abnormalities. No abnormalities in clinical signs, body weight changes, gross findings, mortality, and external appearance were found in all dams and fetuses exposed to 0, 3, and 15 $\mu$g/kg/day of YHB6211. However, in the group treated with 75 $\mu\textrm{g}$/kg/day of YHB6211, maternal body and uterine weights, fetal body weights and length, and the number of live fetuses were significantly decreased and further fetal mortality was remarkably increased. It is suggested that YHB6211 may have no side effect up to the dose level of 15 $\mu$g/kg/day, and there would be no teratogenicity for fetuses of rabbits up to 75 $\mu\textrm{g}$/kg/day even if it may have some toxic effects over 75$\mu\textrm{g}$/kg/day for dams and fetuses of rabbits.

• 대한예방한의학회지
• /
• 제10권2호
• /
• pp.31-49
• /
• 2006

This study was undertaken to investigate the effects of Gyoaesamultang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Gyoaesamultang at dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately, live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of Gyoaesamultang treated group has a tendency to increase compared to that of control group. There were no significant difference in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Gyoaesamultang administered group showed lower early resorption rate than the control group. Neonatal body weight and number of fetus of Gyoaesamultang group were increased to that of control group. The fetuses of dams treated with Gyoaesamultang didn't showed external malformation. Vertebral and sternal variations were observed in Gyoaesamultang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses treated with Gyoaesamultang showed significant difference in the number of caudal vertebra(P<0.01). From these results, it can be concluded that Gyoaesamultang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Gyoaesamultang were shown insignificant changes in bone malformation.

• 대한예방한의학회지
• /
• 제14권2호
• /
• pp.91-104
• /
• 2010

The experiments were undertaken to evaluate the effects of herbal medicine, Bojungiggitang and Gwibitang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Bojungiggitang and Gwibitang at dose of 5ml/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and the internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weights of Bojungiggitang and Gwibitang treated group has a tendency to increase compared to that of control group. There were no significant differences in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation and live fetuses. But Bojungiggitang and Gwibitang administered group showed higher implantation rate than the control group. Also, Bojungiggitang and Gwibitang administered groups showed lower early resorption rate than the control group. And Gwibitang had the higher value in all the other groups in all items. From the sex ratio, the number of females were larger than the number of males in the control group, and more males than females in Gwibitang administered group. Neonatal body weight and the number of fetus of Bojungiggitang and Gwibitang group were higher than that of control group. The fetuses of dams treated with Bojungiggitang and Gwibitang did not show external malformation. Vertebral and sternal variations were observed in Bojungiggitang and Gwibitang administered group compared to the control group. Those variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumbar, sacral and caudal vertebras. From these results, it can be concluded that Bojungiggitang and Gwibitang showed no toxic effects on maternal body weight and the number of live fetuses. There were no significant changes in organ weight, hematological data, and reproductive organs. Although skeletal variations were shown in vertebra and sternum, Bojungiggitang, Gwibitang were shown insignificant changes in bone malformation.

• 한국환경보건학회지
• /
• 제32권4호
• /
• pp.342-352
• /
• 2006

The experiments was undertaken to evaluate the effects of herbal medicine, Dalsaengtang, in pregnant rats and fetuses. Female Sprague-Dawley rats were orally administered with the Dalsaengtang at dose of 5 mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of dalsaengtang treated group has a tendency to increase compared to that of control group. The relative liver and kidney weights of dalsaengtang treated group were also increased to that of control group. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Dalsaengtang administered group showed lower early resorption rate than the control group. From the sex ratio, number of females, bigger than number of males in the control group, and more males than females in Dalsaengtang administered group. Neonatal body weight and number of fetus of Dalsaengtang group were increased to that of control group. The fetuses of dams treated with Dalsaengtang didn't showed external malformation. Vertebral and sternal variations were observed in Dalsaengtang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses showed significant difference in the number of caudal vertebra (P<0.01). From these results, it can be concluded that Dalsaengtang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Dalsaengtang did not shown significant changes in bone malformation.

• 한국환경보건학회지
• /
• 제40권4호
• /
• pp.279-293
• /
• 2014

Objectives: Children are more susceptible to heavy metal toxicity than adults. The purpose of this study was to evaluate heavy metal concentrations in the blood of Korean preschoolers and investigate the association between metals in blood and related factors. Methods: A total of 512 subjects from 36 to 83 months of age were sampled. A questionnaire survey was performed and the levels of lead, mercury and cadmium were measured in the blood samples of all subjects. Their parents were interviewed in order to obtain information on basic characteristics, dietary patterns, socio-economic factors, and indoor/outdoor environment of the preschoolers. Multiple linear regression was used to analyze the association between the above factors and lead, mercury or cadmium concentrations. Results: The geometric mean concentrations of lead, mercury and cadmium in the blood were $1.45{\pm}1.58{\mu}g/dL$, $2.14{\pm}1.74{\mu}g/dL$ and $0.23{\pm}1.91{\mu}g/dL$, respectively. Results from multiple linear regression analysis showed that blood lead levels were associated with birth weight and paternal smoking status. Daily mercury intake from food and maternal education were also shown to influence mercury concentrations in blood. Also, blood cadmium concentrations were associated with maternal age and having a bus garage near the place of residence. Conclusion: This study suggests that smoking status, dietary patterns and the environmental status near the residence should be considered as important factors for preventable sources of heavy metal exposure in preschoolers.

• Toxicological Research
• /
• 제21권4호
• /
• pp.325-332
• /
• 2005

The developmental toxicity of water extract of licorice (Glycyrrhiza glabra) was evaluated in rats. Licorice extract (500, 1,000 or 2,000 mg/kg) was dissolved in drinking water and orally administered to male rats from 9 weeks before mating to the day of copulation, and to females from 2 weeks before mating to gestational day 19. On gestational day 20, the animals were sacrificed for Cesarian section, and maternal and fetal abnormalities were examined. Licorice extract neither induce clinical signs, nor affect the body weight gain, feed and water intake, estrous cycle, copulation and fertility rates, blood $17\beta-estradiol$ level and organ weights of dams. Also, the implantation and development including body weights, absorption and death of embryos and fetuses were not influenced by in utero exposure to licorice. In addition, there were no increases in external, visceral and skeletal abnormalities of fetuses. Taken together, it is suggested that no observed adverse effect level of licorice extract is higher than 2,000 mg/kg, and that long-term in utero exposure to licorice might not cause developmental toxicities of embryos and fetuses.

• 한국환경보건학회:학술대회논문집
• /
• 한국환경보건학회 2005년도 국제학술대회
• /
• pp.73-83
• /
• 2005

Higher methylmercury (MeHg) accumulation and susceptibility to toxicity in the fetus than in the mother at parturition is well known. However, the difference in MeHg exposure to fetus and offspring throughout gestation and suckling is not well established. In the human, the effects of MeHg exposure on pregnant and breast-feeding women remain an important issue for elucidation, especially those of continuous uptake in high-fish-consumption populations. The purpose of this paper was to evaluate the difference in MeHg exposure to fetus and offspring throughout gestation and lactation using our recent animal and human studies data. In the animal study, adult female rats were given a diet containing 5 ${\mu}$g/g Hg (as MeHg) for 8 weeks. Then they were mated and subsequently given the same diet throughout gestation and suckling. On embryonic days 18, 20, 22 and at parturition, the concentrations of Hg in the brains of fetus were approximately 1.5-2.0 times higher than those in the mothers. However, during the suckling period Hg concentrations in the brain rapidly declined to about 1/10 of that during late pregnancy. Hg concentrations in blood also decreased rapidly after birth. In human study, Hg concentrations in red blood cells (RBCs-Hg) in 16 pairs of maternal and umbilical cord blood samples were compared at birth and 3 months of age after parturition. RBCs-Hg concentration in the umbilical cords was about 1.6 times higher than those in the mothers at parturition. However, all the infants showed declines in Hg concentrations throughout the breast-feeding period. The Hg concentration in RBCs-Hg at 3 months of age was about half that at birth. Both the animal and human studies indicated that MeHg exposure to the fetus might be especially high but it dramatically decreases during the suckling period. Therefore, close attention should be paid to the gestation rather than the breast-feeding period to avoid the risk of MeHg to human infants.

• Journal of Nutrition and Health
• /
• 제30권10호
• /
• pp.1195-1202
• /
• 1997

Iodine-rich seaweed soup has been traditionally supplied to postpartum women in Korea. This dietary habit might introduce over-intake of iodine above the recommended requirements, and might provoke postpartum thyroid dysfunction. Although the response to excess iodine intake is highly variable, goiter, hyperthyroidism, hypothyroidism, and thyroiditis could follow the daily intake of 1,500$\mu\textrm{g}$ of iodine. A few studies are available concerning iodine toxicity in Korea. The purpose of this study was to investigate the relationships between the dietary intake of iodine and thyroid function change as well as the incidence of postpartum thyroiditis. One hundred and thirty-seven postpartum women who had experienced normal deliveries were studied. Dietary intake of iodine and excretion concentration of iodine in breast milk and maternal urine were measured . Serum T$_3$, T$_4$, TSH, anti-thyroglobulin antibody, and anti-microsomal antibody were anlayzed 1 week before delivery and 1, 6, 12, and24 weeks after delivery. Iodine intake was analyzed by one-to-one interviews using 24-hr recall and a food frequncy questionnaire. The result showed that the intake of dietary iodine before delivery and 1 and24 weeks after delivery were 483$\mu\textrm{g}$/day, 3367$\mu\textrm{g}$/day, and 1069$\mu\textrm{g}$/day, respectively. The concentration of iodine in urine at the first week after delivery was 63$\mu\textrm{g}$/dL, and 23.9$\mu\textrm{g}$/dL in breast milk . The levels of serum T$_3$ and T$_4$ before delivery were 2.01ng/mL and 11.49$\mu\textrm{g}$U/dL, respectively, showing that the levels were gradually dropping to normal values after delivery. Positive serum anti-thyroglobulin antibody and anti-microsomal antibody appeared in 3 cases. After a 24 week follow-up period , 6 women(10.3%) experienced cases of postpartum thyroiditis, 5 of which were cases of hyperthyroidism and one of which was a case of hypothyroidism. These figures of postpartum thyroiditis are similar to those of other countries.

• Toxicological Research
• /
• 제29권1호
• /
• pp.27-34
• /
• 2013

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.