• Toxicological Research
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• 제17권2호
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• pp.107-114
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• 2001

This study was designed to evaluate a repeated oral dose toxicity of a new hepatotherapeutic agent GODEX in Sprague-Dawley rats. Male and female rats were orally administered with dosages of 500, 100, 20, and 0 /kg/day of GODEX daily for 4 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with GODEX. Gross and histopathological findings revealed no evidence of specific toxicity related to GODEX. These indicate that GODEX may have no side effects and its oral maximum tolerated dose value may be over 500 mg/kg in rats.

• Toxicological Research
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• 제21권3호
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• pp.263-269
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• 2005

This study was performed to investigate repeated-dose toxicities of Clean natural, a new disinfectant, in Sprague-Dawley(SD) rats. In the 4-week repeated oral toxicity study, Clean Natural was orally administered once daily via gavage to male and female rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg body weight for 4-weeks. There were no deaths and clinical signs during the dosing period. In both sexes, there were no statistically significant differences between the administered and control groups in urinalysis indicators and hematological parameters. In serum biochemistry, aspartate aminotransferase(AST) was significantly decreased and sodium content was increased in the 2,000 mg/kg male group, while chlorine was significantly decreased in the 2,000 mg/kg female group. Also, albumin, total cholesterol and total bilirubin were significantly increased in the 2,000 mg/kg male and female group. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver was observed in the 2,000 mg/kg male and female groups. And pigmentation in the spleen was observed in the 2,000 mg/kg male group. In conclusion, four-week repeated oral dose of Clean Natural to rats did not cause apparent toxicological change at the dose less than 2,000 mg/kg body weight. Thus it is suggested that no-observed adverse-effect level(NOAEL) for Clean Natural in rats was considered to be 1,000 mg/kg/day.

• 생약학회지
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• 제50권3호
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• pp.205-218
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• 2019

This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.

• Toxicological Research
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• 제23권4호
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• pp.405-413
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• 2007

This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

• Toxicological Research
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• 제18권4호
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• pp.375-384
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• 2002

Repeated-dose toxicity of hyrubicin ID6105, a novel anthrarycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 week. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However body weight gain of both male and female rats treated with a high dose (l.0 mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoietic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that Long-term administration of ID6105 at high doses over 0.2 mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.96-96
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• 2004

• 대한약침학회지
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• 제13권4호
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• pp.5-41
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• 2010

Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56mg/kg body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7. The proper high dosage of Sweet BV for the thirteen week repeated test in Beagle dogs may be 0.28mg/kg in one time. Conclusion: Above findings suggest that Sweet BV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Toxicological Research
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• 제15권1호
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• pp.9-17
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• 1999

This study was performed to evaluate the subacute toxicity of CJ-50002 (Vibrio Vaccine) in SPF Spraqur-Dawley (SD) rats. Vibrio vaccine was administered orally at a dose level of high (167mg/kg/day), medium (16.7mg/kg/day), and low (16.7mg/kg/day) once a day and repeated fro 4 weeks. Ten males and female rats were assigned to each group. After 4 week administration, no significant dose-dependent changes in body weight, water and food consumption rate or organ weight were noted dependent changes in body weight, water and food consumption rate or organ weight were noted among 4 groups. Urinanalysis, hematology, and serum chemistry, also fail to detect any dose-related change among 4 groups tested. During necropsy and histopathological examination, no specific toxicity related to treated material was found. The result of this study demonstrated that vibrio vaccine when administered orally for 4 weeks at a high dose of 167mg/kg/day, no dose-related toxicity was found in treated make and female rats.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• 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.