• Title/Summary/Keyword: embryo and fetal developmental toxicity

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Developmental and reproductive toxicity assessment in rats with KGC-HJ3, Korean Red Ginseng with Angelica gigas and Deer antlers

  • Lee, Jinsoo;Jeong, Ji-Seong;Cho, Kyung-Jin;Moon, Kyeong-Nang;Kim, Sang Yun;Han, Byungcheol;Kim, Yong-Soon;Jeong, Eun Ju;Chung, Moon-Koo;Yu, Wook-Joon
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.242-251
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    • 2019
  • Background: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. Methods: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. Results and conclusion: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

Embryo and Fetal Developmental toxicity Study on Recombinant Human Epidermal Growth Factor (rhEGF) in Rats (재조합 인간상피세포 성장인자(rhEGF, DWP401)의 배${\cdot}$태자발달 독성 연구)

  • Park, Kui-Le;Han, Soon-Young;Shin, Jae-Ho;Lee, Yoo-Mie;Park, Hee-Jung;Jang, Seung-Jae
    • YAKHAK HOEJI
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    • v.42 no.5
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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.

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Assessment of Embryotoxicity of 2-Bromopropane in ICR Mice

  • Kim, Jong-Choon;Shin, Dong-Ho;Kim, Sung-Ho;Oh, Ki-Seok;Kim, Hyeon-Yeong;Her, Jeong-Doo;Jiang, Cheng-Zhe;Chung, Moon-Koo
    • 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.

Effects of 00 Hz Horizontally Polarized Magnetic Fields on Embryo-fetal Development in SD Rats (SD 랫드의 배 .태자발생에 대한 60 Hz 수평자계의 영향)

  • 정문구;김종춘;명성호;김상범;이동일
    • Toxicological Research
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    • v.17 no.4
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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.

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Embryo and Fetal Developmental Toxicity Study on Gamma-Irradiated Korean Ginseng in Rats (방사선 조사 인삼이 랫드의 기형유발에 미치는 영향에 관한 연구)

  • 박귀례;신재호;김판기;이유미;장성재
    • Toxicological Research
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    • v.17 no.1
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    • pp.27-32
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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 food treatment 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 embryo and fetal developmental toxicity effects in rats. Either EO gas fumigated or $\gamma$-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 7 to 17. 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, food consumption and body/organ weight. No treatment related changes in implantation ratio, litter size, sex ratio and body/organ weight of fetuses were observed. Also, no F1fetuses with external, visceral, head and skeletal mal-formation were observed. The results of this study showed that $\gamma$-irradiated ginseng, up to 30 kGy, has no adverse effects on fetal development of rats.

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Embryo lethality and teratogenicity of 2-Bromopropane in the Sprague-Dawley rat (Sprague-Dawley 랫드에서 2-Bromopropane의 배자치사 및 최기형성 효과)

  • Kim, Jong-Choon;Oh, Ki-Seok;Shin, Dong-Ho;Kim, Sung-Ho;Kim, Hyeon-Yeong;Yun, Hyo-In;Jiang, Cheng-Zhe;Heo, Jeong-Doo;Chung, Moon-Koo
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.657-666
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    • 2003
  • 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 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

Effects of Exposure Period on the Developmental Toxicity of 2-Bromopropane in Sprague-Dawley Rats

  • Shin, In-Sik;Lee, Jong-Chan;Kim, Kang-Hyeon;Ahn, Tai-Hwan;Bae, Chun-Sik;Moon, Chang-Jong;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Jong-Choon
    • 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.

Teratogenicity Evaluation of 2-Bromopropane Using Rat Whole Embryo Culture (랫드 전배아배양법을 이용한 2-Bromopropane의 최기형성 평가)

  • Kim Jong-Choon;Shin Dong-Ho;Kim Sung-Ho;Yang Young-Soo;Oh Ki-Seok;Jiang Cheng-Zhe;Chung Moon-Koo
    • Toxicological Research
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    • v.22 no.2
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    • pp.127-133
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    • 2006
  • Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.

Embryo-Fetal Developmental Toxicity Study of Methoxycinnamidopropyl Polysilsesquioxane (Methoxycinnamidopropyl Polysilsesquioxane의 랫드를 이용한 배.태자 발생독성 연구)

  • Hong, Jeong-Sup;Lim, Jeong-Hyeon;Kim, Kang-Hyun;Park, Myeong-Kyu;Jo, Ki-Yeon;Park, Gil-Jong;Jung, Taek-Kyu;Kim, Ja-Young;Yoon, Kyung-Sup
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.3
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    • pp.247-256
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    • 2011
  • Existing organic UV protection materials seem to be problematic due to their penetration and irritation to skin. Inorganic UV protection materials are also at issue for safety of their nano-type transformation. Therefore, the recent studies of UV protection materials have been focused not only on the effectiveness but also on their safety. One of the UV protection materials in study which have higher safety is the organic-inorganic conjugation type UV protection material. Previously, we have reported the manufacturing process, physical property and UV protection efficiency of methoxychinnamidoprophy poloysilsesquixan as a new cross-linked polymer type UV protection material. In this study, we have evaluated the effect of the methoxychinnamidoprophy poloysilsesquixan on embryo-fetal development in SD rats. This study is expected to show some definite information related to the effect on pregnancy or embryo-fetal abnormality in case of the clinical exposure of the methoxychinnamidoprophy poloysilsesquixan.