• Toxicological Research
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• 제17권1호
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• pp.17-25
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for sterilization of food was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on peri- and postnatal developmental toxicity in rats. Either EO gas fumigated or gamma-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 16 to postnatal day 21. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. No treatment related changes in food consumption, body/organ weight and lactation of dams were observed. Also, no F1 fetuses in external abnormality, physical development, reflex/sensory junctions and behavioral development were found. The results of this study showed that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the peri- and postnatal development of rats.

• 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.

• 대한예방한의학회지
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• 제12권2호
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• pp.27-35
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• 2008

Purpose : The experiments was undertaken to evaluate the effects of Ojeoksan-herbal medicine, in rats' fetus Methods : Female Sprague-Dawley rats were orally administered with the Ojeoksan 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. Results : Neonatal body weight and number of fetus of Ojeoksan group were increased to that of control group. The fetuses of dams treated with Ojeoksan didn't showed external malformation. Vertebral and sternal skeletal variations were observed in Ojeoksan administered group, but compared to the control, those skeletal variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumber, sacral and caudal Conclusion : From these results, it can be concluded that Ojeoksan showed no toxicity effects on number of live fetuses. There were no significant changes in skeletal variations were showed in vertebrate and sternum, Ojeoksan weren't shown significant changes in bone malformation. We need more precise study to investigate the mechanism of early or late resorption by the herbal medicines such as Ojeoksan.

• 한국환경보건학회지
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• 제34권2호
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• pp.161-169
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• 2008

This study evaluates the protective effects of Korean garlic juice against the toxicity of methyl mercuric chloride (MMC) in relation to fetal ossification in pregnant Fischer 344 rats. This study has as its basis, both theory and data that neutral amino acids in garlic juice have protective effects against mercury poisoning. Pregnant rats were dosed in various combination with 20 mg MMC/kg body wt. and 0.5 or 1.0 garlic juice/kg body wt. on the 7th day of gestation. Fetuses were extracted from the dams on 20th day of gestation, and the fetal bones were stained and measured. The results obtained are as follows: 1. Fetal body weights, body lengths, and head length were significantly decreased by as much as 23.5%, 21.3%, 15.5% respectively in 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were almost similar to the controls. 2. The ossification centers were significantly decreased by as much as 35.1% in pelvic phalanges, 53.5% in pectoral phalanges, 74.1% in ternebrae, 76.2% in tail in 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were significantly increased by as much as $81.2{\sim}88.7%$ and $94.8{\sim}98.9%$ of controls. 3. The ossified pectoral girdles were significantly decreased by as much as 66.6% in clavicle, and in other areas $74.2{\sim}87.4%$ in the 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were significantly increased by as much as $81.2{\sim}88.7%$ and $94.8{\sim}98.9%$ of the controls. 4. The ossified pelvic girdles were significantly decreased by as much as 57.1% and 56.1% in two ischium, $67.2{\sim}81.7%$ in metacarpals in the 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were significantly increased by as much as $67.0{\sim}85.6%$ and $90.1{\sim}98.7%$ of the controls. 5. The ossified terenebrae were unchanged or significantly decreased; 0.0% in 5th, 54.1% in 1st, 83.9% in 2nd, 75.0% in 3rd, 72.7% in 4th, 79.8% in 6th of 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were significantly increased by as much as $29.5{\sim}55.1%$ and $54.5{\sim}84.0%$ of the controls. 6. The ossified ribs were significantly decreased by as much as $8.3{\sim}18.0%$ in 20 mg/wt kg methyl mercuric chloride groups (p<0.05). But in the garlic treated groups, they were significantly increased by as much as $87.1{\sim}93.5%$ and $96.3{\sim}99.7%$ of the controls. In conclusion, Korean garlic juice significantly protected against the toxicity of MMC in relation to the fetal ossification in pregnant rats.

• 약학회지
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• 제42권5호
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• pp.534-539
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• 1998

Effect of recombinant human epidermal growth factor (rhEGF, DWP401) on fetal external, visceral and skeletal malformation during organogenesis was examined. Pregnant Sprauge-Daw ley rats were administered with 0.2, 1 and 5mg/kg/day subcutaneously on gestation day 6 through 16. Dams were sacrified at 20th day of gestation. Materal body weight, food consumption and clinical observation were not changed. Significant dose-dependent increase of relative and absolute liver weight were observed in the treatment group, whereas other organ weights were not changed. Placental weight of 1 and 5mg/kg/day group and number of resorption in 5mg/kg/day treatment group were significantly increased. External and visceral malformation of fetuses were not observed with treatment. However, skeletal variations(increase of asymmetry sternebrae, decrease of dumb-bell and asymmetry sternbrae at 5mg/kg/day, and fused stemebrae at 5mg/kg/day) were observed. These results showed that rhEGF (DWP401) may not have embryo and/or fetal developmental toxicity effect in rats.

• 대한약침학회지
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• 제23권3호
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• pp.165-172
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• 2020

Objectives: In the past few years, herbal medicines have gained popularity over synthetic drugs because of their natural source and minimal side effects which has led to a tremendous growth of phytopharmaceuticals usage. With the development of nanotechnology, it provides alternative approaches to overcome several limitations using nano-formulations. In spite of considerable quantity of antianemic preparations with different iron forms available, currently additives are used and represented in modern pharmaceutical market. Iron deficiency anemia is a major global public health problem which particularly affects pregnant women, children and elderly persons. The situation is complicated because of disadvantages and drug side effects from existing antianemic medicines. There is a great demand for the development of new antianemic preparations. Green synthesis of iron oxide nanoparticles, possess high potential in this field. Methods: Our study focuses on developing green synthesis of iron oxide nanoparticles (IONPs) of 10-50 nm with spherical shape where different dosages were used -1 mg/kg, 10 mg/kg and 100 mg/kg for exposure in Wistar albino female rats for 28 days. The toxicity was assessed using various parameters such as measurements of the rat body and organ mass, hematology, biochemical evaluation and histopathological examinations. Results: No significant differences were observed in body and organ weights. Hematological indices also indicated no significant differences whereas biochemical factors showed increase in levels of direct bilirubin and globulin of medium as well as high dose and SGPT levels were increased only in high dose. The major organs (heart, kidney and liver) showed histopathological alterations in 10 and 100 mg/kg whereas brain showed only in 100 mg/kg. Conclusion: The toxicity of IONPs was found to be more significant when the concentration was increased; however, low doses can be used for further investigation as an antianemic preparation.

• Toxicological Research
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• 제29권1호
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Journal of Ginseng Research
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• 제26권3호
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• pp.139-144
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• 2002

수태는 많은 신체적인 기능들의 높은 에너지 요구 및 산소요구량 증가로 인하여 생리적인 변화를 수반한다. 때문에 산소 섭취량 및 이용이 증가하여 산화적인 스트레스의 증가를 기대할 수 있다. 수태중에 발생되는 free radical에 대하여 홍삼사포닌 투여가 간 항산화효소의 활성에 미치는 영향을 연구하였다. 수태중에 superoxide dismutase(SOD)의 활성은 전반적으로 감소하는 경향을 나타냈으며, 사포닌 투여군은 대조군에 비하여 유의한 변화가 관찰되지 않았다. 그리고 glutathione peroxidase(GPX) , gluthatione reductase (GRD)와 catalase의 활성도는 수태중에 감소하는 경향을 나타냈으며, 반면에 사포닌 투여군은 대조군 비하여 GRD 및 catalase의 활성도에 유의한 변화를 나타냈다. 사포닌 투여군의 GPX의 활성도는 대조군에 비하여 감소하는 경향이 다소 적게 나타났다. 수태중 대조군의 glutathione-S-transferase (GST) 활성도는 항상성을 유지하기 위해 증가하는 경향을 나타냈으며, 사포닌 투여군도 대조군에 비하여 이 효소의 활성도가 더욱 증가하는 경향을 나타냈다. 분만 후 대조군 및 사포닌 투여군은 정상수준으로 회복되었다. 수태와 같은 생체변화에도 불구하고 수태한 흰쥐의 간 항산화 효소활성에 대한 사포닌의 영향은 산소독성에 대하여 모체간을 보호해주는 생리적 항상성의 적응메카니즘에 의하여 조절되는 것으로 보인다.

• 대한수의학회지
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• 제34권3호
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• pp.601-607
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• 1994

This study was carried out to investigate the potential of phenol to induce embryotoxicity in the Sprague-Dawley rat. Seventy mated rats were distributed among three treated troups, a vehicle control group and a negative control group. Phenol was at dose levels of 20, 60 and 180mg/kg/day adminsistered by gavage to pregnant rats three times per day from days 7 to 12 of gestation. All dams were subjected to the caesarean section on day 20 of gestation. At 120mg/kg, dams exhibited decreased locomotivity. In addition, both weight reduction and retarded ossification of fetuses were observed. There were no signs of maternal toxicity or embryotoxicity at 20 and 60mg/kg. The results show that phenol induces fetal growth retardation at maternally subtoxic dose in rats.

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