• Toxicological Research
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• 제13권4호
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• pp.423-433
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• 1997

The acute and subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (new DDB), hepatitis therapeutics, were investigated in SD rats. In the acute toxicity study, body weights and clinical signs were observed for 7 days after the intravenous injection of new DDB at doses of 140, 182, 236, 307 and 400 mg/kg(r=1.3). Death. Severe convulsion, tremor and decrease motor activity were observed in almost treated groups (except the 140 mg/kg treated group). Changes of body weight in treated groups were not significantly different from control group. Autopsy of survived animals revealed no abnormal gross findings related to new DDB. As a results, the $LD_{50}$ values of new DDB were 244.1 mg/kg for male and 232.5 mg/kg for female. In subacute toxicity study, body weights and clinical signs were observed after intravenous injection of new DDB at doses of 57, 75 and 100 mg/kg/day for 28 days. Death, decrease motor activity and tremor were observed above 75 mg/kg treated groups. Statistically significant changes were observed in hematological and biochemical parameters of new DDB-treated groups; however, these changes were within normal range and had no relationship with dosage. Several abnormal findings were observed in microscopic examination of tissue; however, these findings were not caused by new DDB but environmental factor. The no toxic dose level of new DDB were estimated to be 57 mg/kg/day in this study.

• Toxicological Research
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• 제16권3호
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• pp.239-253
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• 2000

This study was carried out to evaluate the three months subacute intravenous toxicity of water soluble dimethyl dimethoxy biphenylate derivative (DDB-S), a newly formulated therapeutic agent for hepatitis, in Beagle dogs. Groups of 12 male and 12 female dogs were given different dosage of DDB-S, 10 mg/kg/day (high dose group), 5 mg/kg/day (middle dose group), 2.5 mg/kg/day (low dose group) and 0 mg/kg/day (control group) for three months by intravenous route. 1n the three months intravenous toxicity study, there were neither dead animals nor significant changes of body weights during the experimental period. 1n addition to, no significant DDB-S related changes were found in clinical signs, urinalysis and other findings. Statistical changes were observed in hematological. biochemical, partial thromboplastin time (PIT) and organ weight parameters of treated groups. However, these alteration had no relationship with dosage. No histopathological lesions were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in Beagle dogs might be over 10 mg/kg/day in this study.

• Toxicological Research
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• 제16권2호
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• pp.151-161
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• 2000

The Three months subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (DDB-S), newly formulated therapeutic agent for hepatitis, was invesgated in SD rats. The body weight and clinical signs were observed after intravenous injection of DDBs at doses of 57, 75 and 100 mg/kg/day for three months. Decrease in motor activity and tremor were observed above 75mg/kg treated groups. Statistically significant changes at serum biochemical analysis were found in some group, how-ever, those changes were within the normal range and had no relationship with dosage. There was no abnormal morphological and pathological findings in relation to DDB-S treatment. The no observable adverse effect level of DDB-S in rats was estimated to be 57 mg/kg/day in this study.

• 대한약침학회지
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• 제6권2호
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• pp.7-27
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• 2003

Objective : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled) in mice and rats. Method : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture caused negligible toxicity, and had anti-tumor effects in mice.

• Toxicological Research
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• 제12권2호
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• pp.309-318
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• 1996

This study was conducted to investigate the subacute intravenous toxicity of rHu-EPO in Sprague-Dawley rats. rHu-EPO was daily administered to male and female rats for 30 days with different dose levels(100, 500, 2,500 unit/ kg). After the administration period of 30 days, 5 males and 5females rats per each dose group were assigned for recovery period of additional 30 days. There were no clinical signs compared with control group but slight decrease in spontaneous motor activities and locomotions were observed at high dose groups of males and females. In males, feed consumption was reduced at 500 unit/kg and body weight gain was retarded. In the administration sites of tail, focal congestion was observed in a few animals treated with rHu-EPO. No deaths were occurred during the course of study. In hematological examination. a significant increase of hemoglobin and hematocrit was observed in the males and females rats receiving high dose of rHu-EPO. rHu-EPO administration for 30 days showed a marked decrease in glucose concentration. At the highest dose groups, there was a significant incerase in the weights of spleens in both sexes. but this was considered to be related to its pharmacological activity. These results indicate that rHu-EPO does not induce any significant toxic effect on Sprague-Dawley rats for 30 days.

• 생명과학회지
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• 제23권11호
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• pp.1388-1396
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• 2013

본 연구는 인공재배 상황버섯 자실체 추출물인 금사목질진흙버섯 자실체 추출물의 mouse sarcoma cells인 S-180 세포에 대한 정맥 투여 시 항암 효과와 급성독성 및 4주 아 급성 독성에 대한 보고이다. 금사목질진흙버섯 자실체 추출물의 항암효과는 250 mg/kg에서 대조군 대비 42.7%의 크기로 가장 높은 효과를 나타내었으며, 농도 의존적인 경향을 나타내었다. 급성 독성에서는 $LD_{50}$치가 632.84 mg/kg (♂)과 814.48 mg/kg (♀)로 나타났으며, 이자와 장기의 무게비가 증가하는 현상이 나타나, 영향이 있는 것으로 추측되었다. 4주 아 급성 독성 시험에서 $LD_{50}$치는 355.41 mg/kg (♂)과 383.53 mg/kg (♀)로 나타났으며, 특히 250 mg/kg 투여군에서는 간의 무게 비가 2배 정도 증가하는 현상과 황색 반점이 나타났다. 특히 125 mg/kg 이상 투여군에서는 점프 능력과 민첩성 등의 운동 능력이 현저히 증가되는 현상이 관찰되었으며, 이에 대한 정확한 메카니즘은 확인할 수 없었다. 이상의 결과를 바탕으로 금사목질진흙버섯 자실체 추출물에 대한 표준물질 정제 과정을 통한 작용기전과 운동능력 향상에 대한 실험 등이 추가된다면 유효 농도에서 독성이 낮으면서도 암을 제어할 수 있는 새로운 천연물 신약의 후보 물질로 이용될 가능성이 있는 것으로 판단된다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.169-169
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• 2001

This study was designed to evaluate an acute and subacute intravenous dose toxicity of a new cephalosporin antibiotic agent, IDC-7181 in 7-week-old Sprague-Dawley rats. IDC-7181 was intravenously injected to rats at dose levels of 0, 3.2, 16, 80, 400 and 2, 000 mg/kg/day for single dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4 week-repeated dose toxicity study. All rats survived throughout the study periods.(omitted)

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.182-190
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• 1998

DA-3585 is a recombinant human erythropoietin produced by Dong-A pharmaceutical Co. Ltd. using recombinant DNA technique. Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. In this study, we examined acute and subacute toxicity of DA-3585 in rats. DA-3585 was intravenously administered to rats at dose levels of 0, 6,250, 12,500 and 25,000 lU/kg for single dose toxicity study and at dose levels of 0,100,500 and 2,500IU/kg daily for 4 week-repeated dose toxicity study. In the single dose toxicity study, there were no death, clinical signs and changes in body weight gain related to the treatment. Necropsy revealed no evidence of toxicity related to DA-3585, In the repeated dose toxicity study, all the rats survived throughout the study. There were no treatment-related changes in clinical signs, food and water intake, and body weight. Hematological examination showed increases in the number of erythrocytes, hemoglobin concentration, hematocrit value and mean corpuscular volume, and decrease in the number of platelet in 500 and 2,500 lU/kg dosed groups. Extramedullary hematopoiesis in the spleen and erythroid hyperplasia in the bone marrow were noted as treatment-related histological changes. Toxicologically significant changes were not observed in blood biochemistry, urinalysis, organ weights and in any other examinations. The treatment-related changes observed in this study were hematological or histological changes associated with pharmacological effects of DA-3585. On the basis of the results of this study, LD5n value of DA-3585 was above 25,000 lU/kg and the no-observed-adverse-effect-level was estimated to be 100 lU/kg.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.49-54
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• 2004

The present study was conducted to investigate the potential subacute toxicity of CKD-602 by a 5-day repeated intravenous administration in Sprague-Dawley rats. CKD-602 was administered intravenously to male rats at dose levels of 0, 0.08, 0.2, and 0.5 mg/kg for 5 days. Studies included general observation, body weight changes, ophthalmoscopic examination, hematology, se겨m biochemistry, gross findings at necropsy and organ weight measurement. There were no deaths in any treatment group and treatment related clinical sign was depilation in the 0.5 mg/kg groups. The decrease or suppression of body weight was also observed dose-dependently in all treatment groups. Decreased leukocyte in all treatment groups, decreased platelet in the above 0.2 mg/kg groups and increase in the serum levels of total cholesterol in the 0.5 mg/kg group were considered as a treatment related toxic effects. Decreased weight of thymus in all treatment groups anti decreased weight of spleen in the above 0.2 mg/kg group were observed. The intravenous administration of CKD-602 caused depilation and decreased weight and had toxic effect on the leukocyte, platelet, spleen and thymus. In the condition of this study, the target organs were spleen and thymus and the toxic effect level was determined to be 0.2 mg/kg, but no-observed-adverse-effect level (NOAEL) was considered to be lower than 0.08 mg/kg.

• Toxicological Research
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• 제14권3호
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• pp.435-441
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• 1998

Alginase$Alginase^{ⓡ}$ (Arginine esterase) is one of the snake venoms which is mainly consisted of arginine esterase and acts as a thrombus -forming inhibitor/thrombus-lysin. These present studies were performed to investigate of the acute and subacute toxicity of the Alginase$Alginase^{ⓡ}$ in rats. In acute toxicity study, rats were single administered intravenously with dosages of 0.001, 0.01. 0.1, 1 and 10U/kg B.W. and examined the number of death, clinical sign, body weight and pathological change for 7days after administration of Alginase$Alginase^{ⓡ}$. At maximum dose level (10U/kg B.W.), Alginase$Alginase^{ⓡ}$ induced symptoms of shock with cyanosis and dyspnea. But these symptoms dissappeared after 30~50 minutes and we could not find any other toxic effect in rats. Therefore, $LD_{50}$ Value of Alginase was over 10U/kg B.W. in rats. In four-week intravenous toxicity study of Alginase$Alginase^{ⓡ}$, rats were administered intravenously seven days per week for 28 days, with dosages of 0, 0.0125, 0.125 and 1.25U/kg B.W./day, respectively. Alginase$Alginase^{ⓡ}$ did not caused any death and showed any clinical signs in rats. No significant Alginase$Alginase^{ⓡ}$ -related changes were found in feed uptake, water consumption, hematology, serum biochemistry, urinalysis, ocular examination, organ weight and histopathological examination. From the results, Alginase$Alginase^{ⓡ}$ seems not to have any toxic effect in rats when it were given daily intravenous injections below the dosage 1.25U/kg B.W./day for four weeks.