• Title/Summary/Keyword: Fetal toxicity

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Male Reproductive Toxicity of DA-125, a New Anthracycline Anticancer Agent, in Rats (수컷랫드에 있어서 새로운 안트라사이클린계 항암제 DA-125의 생식독성 연구)

  • 김종춘;김갑호;신호철;정문구
    • Toxicological Research
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    • v.14 no.2
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    • pp.193-203
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    • 1998
  • The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.

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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.

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.

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.

Evaluation of Maternal Toxicity in Rats Exposed to Multi-Wall Carbon Nanotubes during Pregnancy

  • Lim, Jeong-Hyeon;Kim, Sung-Hwan;Lee, In-Chul;Moon, Chang-Jong;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Hyoung-Chin;Kim, Jong-Choon
    • Environmental Analysis Health and Toxicology
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    • v.26
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    • pp.6.1-6.8
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    • 2011
  • Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results: All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions: The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

The Screening Condition for the Immune Regulatory Responsor Using Mouse Fetal Thymic Organ Culture (쥐의 태아 흉선 조직 배양을 이용한 면역조절제 검색방법 확립)

  • Lee, Seung-Gak;Song, Min-Dong;Lee, Kwang-Ho
    • Korean Journal of Pharmacognosy
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    • v.28 no.4
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    • pp.286-292
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    • 1997
  • We studied the screening condition for immune regulatory responsor. We focused on the T-lymphocytes leer this purpose. Mouse fetal thymic organ culture (FTOC) system and flow cytometric analysis were mainly used in this experiment. Even if FTOC is carried out in vivo condition, the pattern of thymic development in the condition of FTOC is similar to that of in vivo condition. In this regard, FTOC system might be very powerful tool to screen the immune regulator, especially concerning on T cells. To establish the optimum condition of FTOC to screen the Immune regulator, we focused on the optimum amount of dose and culture period. The cell number and surface antigens on T cells were also analysed by using hemacytometer and flow cytometer. To monitor the differentiation event, anti-CD3, anti-CD4 and anti-CD8 antibodies were used. Alkoxyglycerol and Phellodendri Cortex were used fur positive and negative control, respectively. Astragalus membranceus was used as test sample. From our analysis, we reached to conclusions that the best dose of extract is $50\;{\mu}g/ml$ of culture medium, the best culture period is for 9 days, and ethanol used as solvent has no toxicity to FTOC.

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Embryotoxicity and Toxicokinetics of the Antimalarial Artesunate in Rats

  • Chung, Moon-Koo;Yu, Wook-Joon;Lee, Jin-Soo;Lee, Jong-Hwa
    • Toxicological Research
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    • v.29 no.1
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    • pp.27-34
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    • 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.

Fetal growth retardation induced by flupyrazofos, a new organophosphorus insecticide, in rats.

  • Chung, Moon-Koo;Kim, Jong-Choon;Han, Sang-Seop
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.122-122
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    • 2001
  • Flupyrazofos is a new type of pyrazole organophosporus insecticide, which has a high activity against the diamond-back moth (Plutella xylostella). The potential of this agent to induce developmental toxicity was investigated in the Sprague-Dawley rat.(omitted)

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PRE- AND POSTNATAL TOXICITY EVALUATION OF 60 Hz HORIZONTALLY POLARIZED MAGNETIC FIELDS IN RATS

  • Chung, Moon-Koo;Kim, Jong-Choon;Myung, Sung-Ho;Han, Sang-Seop
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.133-133
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    • 2002
  • Recently, there is an increasing nationwide concern in Korea that exposure to electric and magnetic fields (MF) in the home environment may not be safe in humans. We previously demonstrated that exposure of MF during the entire period of pregnancy did not induce any adverse effects on both pregnant dams and embryo-fetal development in rats.(omitted)

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