• Toxicological Research
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• v.18 no.4
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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.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.61-68
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• 2008

In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

• Toxicological Research
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• v.23 no.4
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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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• v.21 no.3
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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.

• Korean Journal of Veterinary Research
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• v.43 no.1
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• pp.57-66
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• 2003

Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

• Toxicological Research
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• v.20 no.4
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• pp.349-357
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• 2004

This study was performed to evaluate repeated-dose toxicities of CONP01 in Sprague-Dawley rats. CONP01, a new antiarthritic agent was administered orally to rats at dose levels of 0, 125, 500 and 2,000 mg/kg/day for 4 weeks. In present study, there were no dose response changes in mortality, clinical signs, body weight changes, food and water consumption, ophthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with CONP01. Gross and histopathological findings revealed no evidence of specific toxicity related to CONP01. These result suggest that no observed adverse effect level (NOAEL) of CONP01 may be over 2,000 mg/kg in rats.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.111-121
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• 2010

In order to investigate the preliminary repeat oral dose toxicity and to determine the highest dosage for further 4-week repeated dose toxicity test, Low Molecular Weight Fucoidan (LMF) has been showed various pharmacological effects, was orally administered to female and male rats, once a day for 14 days at dose levels of 2,000, 1,000, 500 and 0 (vehicle control) mg/kg (body weights) in a volume of 10 ml/kg. The mortality and changes on the body weights, clinical signs, hematology, serum biochemistry and gross observations were monitored with organ weight and histopathology of principle organs. As the results of 14-day repeated oral treatment of LMF, no LMF treatment related mortalities were detected up to 2,000 mg/kg in both male and female rats, respectively. In addition, no noticeable changes on the body weight and clinical signs were detected except for significant decreases on the body weights and gains restricted to male 2,000 mg/kg treated groups as compared with male vehicle control. No meaningful changes on the organ weights, hematological, serum biochemistrical, gross and histopathological findings were observed. Therefore the highest dosage in the 4-week repeated dose toxicity test is suggested as 2,000 mg/kg in both female and male rats, respectively.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.171-171
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• 2002

This study was carried out by an Korean GLP laboratory to assess the combined repeated dose, reproduction and developmental toxicity of benzoyl peroxide for OECD SIDS(Screening Information Data Set) program. Male and female Sprague Dawley rats were exposed to benzoyl peroxide at levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for male and for 41-51 days for female.(omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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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)

• 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.