• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.18-26
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• 2014

Objectives: This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV) in Sprague-Dawley (SD) rats. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: (1) Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2) The rats in the high-dose group showed no significant changes in weight compared to the control group. (3) No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs), and biochemistry were observed among the recovery groups. (4) No changes in organ weights were observed during the recovery period. (5) Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion: The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.45-50
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• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• The Journal of Internal Korean Medicine
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• v.35 no.3
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• pp.223-243
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• 2014

Objectives: To provide information on the safety of GST (GamiSasangja-tang; CnidiiFructus, Sophora Root, Angelica Gigas Root, Clematidis Radix, Stemonae Radix, Spirodelae Herba), we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of GST in Sprague-Dawley rats. Methods: Female and male rats were treated with GST at oral doses of 1,250, 2,500, and 5000 mg/kg. The GST was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. The rats were then monitored for 4 extra weeks to determine recovery time after the study period. Results: We found no mortality or abnormalities among clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights or histological markers in any of the rats tested. Conclusions: The no-observed adverse effects level (NOAEL) is considered as over 5000 mg/kg for male and female rats.

• Journal of Oriental Neuropsychiatry
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• v.23 no.3
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.27-37
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• 2021

Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery test of standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30 % ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• 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.

• Biomolecules & Therapeutics
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• v.2 no.2
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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.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.132-132
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• 2003

• Toxicological Research
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• v.22 no.2
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• pp.135-144
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• 2006

This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.