• Title/Summary/Keyword: 13-week repeated dose toxicity

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Safety Evaluation of Korean Mistletoe Extract (한국산 겨우살이 추출물의 안전성 평가)

  • Kim, Inbo;Jeong, Ju-Seong;Yoon, Taek Joon;Kim, Jong Bae
    • The Korean Journal of Food And Nutrition
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    • v.26 no.3
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    • pp.383-390
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    • 2013
  • Mistlero C was shown to be non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test and a combined in vivo mammalian erythrocyte micronucleus test. In a bacterial reverse mutation assay, no significant increases in the number of revertant colonies, compared to the negative control, was detected in $5,000{\mu}g/plate$ of Mistlero C. In addition, with Mistlero C, no changes were shown in the number of micronucleated polychromatic erythrocytes (MNPCE) among 2,000 polychromatic erythrocytes compared to the negative control. Mistlero C was administered orally in rats to investigate acute toxicity. The $LD_{50}$ values in rats were above 2,000 mg/kg. In a repeated dose, 13-week, oral toxicity study conducted in rats, no compound-related adverse effects were shown at doses of Mistlero C of up to 1,000 mg/kg body weight/day. The results of these studies support the safe use of Mistlero C in food for human consumption.

Effect of Lead on Ultrastructure and Enzyme Activities in Mouse Liver and Kidney (납(Pb)이 생쥐 간과 신장의 미세구조 및 몇가지 효소 활성에 미치는 영향)

  • Lee, S.I.;Yoo, C.K.;Choe, R.S.
    • Applied Microscopy
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    • v.15 no.1
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    • pp.13-30
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    • 1985
  • This study was undertaken to investigate the effect of lead on organisms. Mice received 15mg or 30mg of lead acetate per kg body weight every day for 1, 2 or 3 weeks, and the livers and kidneys were removed 24h after repeated injections. The livers and kidneys were used as sources for measurement of enzyme activities and for observation of alterations in ultrastructure. It was observed that body weights of mice treated with lead acetate were decreased when compared with those before treatment. This decrease in body weight was proportional to dose. The enzyme activities of succinate and malate dehydrogenases of experimental group that was treated with lead acetate for 1 week were nearly unchanged when compared with controls, but the enzyme activities of experimental group that was treated with lead acetate for 2 or 3 weeks were lower than those of controls. Changes in the enzyme activities were dependent on, but were not proportional to dose. Histologic examination of livers and kidneys after lead treatment showed that lead compound was accumulated and damaged in nucleus and mitochondria mainly. It was also observed that intranuclear inclusion bodies were formed only in epithelial cell of kidney proximal tubule after lead treatment. The overall changes in the ultrastructure were much greater in the livers than in the kidneys. From the above results, it nay be possible to conclude that the lead results in the decrease in body weight, reduction in the succinate dehydrogenate and malate dehydrogenase activities, and damages in the ultrastructure of kidney and liver in mouse. The presence of intranuclear inclusion bodies only in the kidney implies that these bodies protect the kidney from lead toxicity to some extent.

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Toxicity Studies of DA-l25, an Anthracycline Antitumor Antibiotic : Intravenous Repeated Doses for 26 Weeks in Beagle Dogs (Anthracycline계 항암성 항생물질 DA-125의 Beagle dog에 대한 26주 반복정맥투여독성시험)

  • 차신우;박종일;정태천;신호철;하창수;김형진;양중익;한상섭;노정구
    • Biomolecules & Therapeutics
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    • v.4 no.2
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    • pp.127-137
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    • 1996
  • This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

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