• Title/Summary/Keyword: 13 weeks repeated dose toxicity

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A 4-Week, Repeated, Intravenous Dose, Toxicity Test of Mountain Ginseng Pharmacopuncture in Sprague-Dawley Rats

  • Lee, Kwangho;Yu, Junsang;Sun, Seungho;Kwon, Kirok;Lim, Chungsan
    • Journal of Pharmacopuncture
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    • v.17 no.4
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    • pp.27-35
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    • 2014
  • Objectives: Mountain ginseng pharmacopuncture (MGP) is a pharmacopuncture made by distilling extract from mountain cultivated ginseng or mountain wild ginseng. This pharmacopuncture is injected intravenously, which is a quick, lossless way of strongly tonifying Qi function. The present study was undertaken to evaluate a 4-week, repeated, intravenous injection, toxicity test of MGP in Sprague-Dawley (SD) rats. Methods: Twenty male and female 6-week-old SD rats were used as subjects. We divided the SD rats into 4 groups: the high-dosage (10 mL/kg), medium-dosage (5 mL/kg), low-dosage (2.5 mL/kg) and control (normal saline) groups. MGP or normal saline was injected intravenously into the caudal vein of the rats once daily for 4 weeks. Clinical signs, body weights, and food consumption were monitored during the observation period, and hematology, serum biochemistry, organ weight, necropsy, and histological examinations were conducted once the observations had been completed. Results: No mortality was observed in any of the groups during the observation period. No changes due to MGP were observed in the experimental groups regarding clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weight and necropsy. No histological changes due to MGP were observed in any of the male or female rats in the high-dosage group. Conclusion: During this 4-week, repeated, intravenous injection, toxicity test of MGP in SD rats, no toxic changes due to MGP were observed in any of the male or female rats in the high-dosage group. Thus, we suggest that the high and the low doses in a 13-week, repeated test should be 10 mL/kg and 2.5 mL/kg, respectively.

13 Weeks Repeated-Dose Toxicity Studies of the Siho(Bupleuri Radix) in Rats

  • Myung Sil Hwang;Dong Han Shin;Young Na Yum;Jin Hong Ahn;Jun Chul Park;Ji Sun Lee;Yun Jin Park;Ji On Kim;Shin Hee Kim
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.55-55
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    • 2003
  • The Bupleuri Radix, called as "Siho" in Korea has been widely used in Korea, China, and Japan as Traditional Herbal Medicine since ancient times and currently. Although saikosaponins isolated from the Bupleuri Radix had metabolic and anti-inflammatory action, it's toxicity was not screened completely. Recently, many herbal medicines are imported from China but safety of these was not evaluated. (omitted) (omitted)

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Thirteen-week Repeated Oral Dose Toxicity Study of WK-38 in Rats (랫트에서 WK-38에 대한 13주 반복경구투여 독성에 관한 연구)

  • Chang, Bo-Yoon;Kim, Yoon-Chul;Kang, Dae-Gill;Lee, Ho-Sub;Kim, Sung-Yeon
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.169-176
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    • 2008
  • The subcronic toxicity of WK-38, a herbal preparation for the atherosclerosis, was examined in male and female Sprague-Dawley rats. WK-38 is composed of Rhei Rhizoma, Magonoliae Cortx, Moutan Cortex Radicis. Rats were treated with the test substance at a dose of 5 mg/kg, 50 mg/kg and 500 mg/kg intragastrically for 13 weeks. Control rats were treated with vehicle only. No death and abnormal clinical signs were observed throughout the administration period. Also there was no difference in net body weight gain, food and water consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of the WK-38. Hematological findings and biochemical examination revealed no evidence of specific toxicity related to WK-38. The results suggested that under the condition employed in this study no observation effect level (NOEL) of WK-38 would be 500 mg/kg/day.

Subacute Toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in rats (랫드에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 아급성독성시험에 관한 연구)

  • Kim, Hyoung-Ook;Kang, Kyung-Sun;Shin, Dong-Jin;Cho, Jae-Jin;Kim, Bae-Hwan;Seo, Kwang-Won;Nam, Ki-Hoan;Lee, Yong-Soon
    • Toxicological Research
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    • v.8 no.2
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    • pp.217-233
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    • 1992
  • This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

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Study on the Acute and Sub-Acute Inhalation Toxicity of 1-Bromopropane in SD Rats (Rat를 이용 1-Bromopropane의 급성 및 아급성 흡입독성 연구)

  • Kim, Hyeon-Yeong;Jeong, Jae-Hwang;Chung, Yong-Hyun;Lee, Yong-Muk;Sur, Gil-Soo
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.8 no.2
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    • pp.272-288
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    • 1998
  • The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ; 1. The median lethal concentration($LC_{50}$) was estimated 14,374 ppm(confidence limit 95% ; 13,624~15,596 ppm) in acute inhalation. Abnormal clinical signs related to the 1-BP were not observed with the acute inhalation dose. Gross findings of necropsy revealed no evidence of specific toxicity related to the 1-BP. 2. By sub-acute inhalation the body weights of male and female were significantly reduced(p<0.001) by the dose of 1,800 ppm compared with control group, while the relative weights of liver were significantly increased(p<0.001) in both sexes. However there were no significant variation in food consumption, urine biochemistry, hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-BP were not shown. No toxicologic lesions were observed by the histopathological test.

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Thirteen Weeks Repeated Oral Dose Toxicity Study of Oplopanax elatus (Nakai) Nakai Hydrothermal Extract Powder in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 땃두릅나무 열수추출물 분말의 13주 반복 경구투여 독성에 관한 연구)

  • Yoo, Nam Ho;Kwon, Yongsoo;Chun, Hyeon Soo;An, Kyu Sup;Kim, Hye Jin;Ryu, Hyeon Yeol;Lee, So Min;Song, Kyung Seuk;Park, Byung Jun;Kim, Myong Jo
    • Korean Journal of Pharmacognosy
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    • v.50 no.4
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    • pp.260-271
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    • 2019
  • This study aimed to evaluate the safety of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder. It was conducted using male and female Sprague-Dawley (SD) rats. The test group was established with dose of 500 (low-dosage group), 1,000 (medium- dosage group), and 2,000 (high- dosage group) mg/day. These are investigated that number of dead animals, general symptoms, weight changes, food consumption, ophthalmological examination, urinalysis, urine volume, hematological values, plasma coagulation time values, serum biochemical values, absolute organ weight, relative organ weight and histopathological finding during the experiment. As a result of the above, toxicological changes were not observed. Therefore, the non-toxic content of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder is determined to be 2,000 mg/kg/day, and target organ was not observed.

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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A 90-day Safety Study (Repeated-Dose Oral Toxicity Study) of Genetically Modified ${\beta}$-Carotene Biofortified rice in Sprague-Dawley Rats (SD 랫드에서 베타카로틴강화미의 90일 반복투여 경구독성시험)

  • Park, Soo-Jin;Jeong, Mi-Hye;Lee, Si-Myoung;Kim, Mi-Kyoung;Park, Kyung-Hun;Park, Jae-Yup
    • The Korean Journal of Pesticide Science
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    • v.15 no.3
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    • pp.278-288
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    • 2011
  • This study was conducted to evaluate the safety of ${\beta}$-carotene biofortified rice, a genetically modified organism (GMO) developed by Rural Development Administration. ${\beta}$-carotene biofortified rice were exposed on Sprague-Dawley rats for 13 weeks. All rats survived until the end of the exposure period. There were no biologically significant differences in body weight, feed and water consumption, weight gains and feed efficiency. There were no clinical signs of toxicity attributable to exposure to GM rice. Mild decreases in AST, ALT, TG levels were observed in Group II (25% GM rice (w/w) and Group III (50% GM rice (w/w), both in females and males. Results of histopathological changes treated with the ${\beta}$-carotene biofortified rice had no significant differences between the control and treatment groups. Based on these results, we deemed that genetically modified ${\beta}$-carotene biofortified rice was as safe as conventional rice.

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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