• Toxicological Research
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• v.20 no.2
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• pp.123-129
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• 2004

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

• Toxicological Research
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• v.31 no.1
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• pp.77-88
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• 2015

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.12-22
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• 1997

Intravenous and oral acute toxicity tests in ICR mice and SD rats and percutaneous acute toxicity tests in SD rats and NZW rabbits were conducted to evaluate the toxicity of DA-5018 and DA-5018 cream, respectively Clinical signs observed in mice and rats after the administration of DA-5018 were similar regardless of administration route. The observed clinical signs were jumping, wild running, lacrimation, ataxia, reddening of extremities and ears, ventral or lateral recumbency, respiratory distress, cyanosis, convulsion and death. Pulmonary enlargement and hemorrhage were observed in the animals died immediately after the dosing of DA-5018. At terminal necropsy, pulmonary enlargement and hemorrhage, corneal opacity and focal scabbing and depilation around nose were seen. LD$_{50}$ Values of DA-5018 are 11.5 mg/kg (mice, male), 12.6 mg/kg (mice, female), 88.3 mg/kg (rat, male) and 73.2 mg/kg (rat, female) in oral toxicity tests and 11.0 mg/kg (mice, male), 18.7 mg/kg (mice, female), 0.12 mg/kg (rat, male) and 0.32 mg/kg (rat, female) in i.v. toxicity tests. In the percutaneous acute toxicity tests of DA-5018 cream, no deaths occured in all the tested groups during 14-day observation period. There were also no abnormalities in the general conditions, body weight changes and on necropsy findings in all groups. LD$_{50}$ values of 0.1 ~0.9% DA-5018 creams in male and female rats and rabbits are >2000 mg/kg./kg.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.261-271
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• 1996

It has been reported that G009, polysaccharide isolated from Ganoderma lucidum IY009 has various pharmacological effects, such as antinflamatory, antiviral, anticarcinogenic and immunmodulation effects. The purpose of this study was to determine the subacute toxicity of orally administered G009 in Sprague-Dawley rats. Groups of 40 male and 40 female rats were gavaged with 0, 500, 1,000 or 2,000 mg/kg/day for 30 days. No drug-related deaths and clinical morbidities were resulted. There was no drug-related effect on the body weight gain, food consumption and water consumption. Statistically significant changes were observed in several hematological and biochemical parameters of G009-treated groups; however, most of these changes were within normal range and had no relationship to dosage. Urinalysis and bone marrow biopsy showed no remarkable changes in all treated groups. Gross necropsy and hisopathology revealed no evidence of specific toxicity related to G009. Our data indicate that no-observed effect level of G009 is estimated to be above 2,000 mg/kg/day in rats.

• Nutrition Research and Practice
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• v.11 no.6
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• pp.452-460
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• 2017

BACKGROUD/OBJECTIVES: Turanose, ${\alpha}$-D-glucosyl-($1{\rightarrow}3$)-${\alpha}$-D-fructose, is a sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose, acute and subchronic oral toxicity studies were conducted with ICR mice. MATERIALS AND METHODS: For the acute oral toxicity study, turanose was administered as a single oral dose [10 g/kg body weight (b.w.)]. In the subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg b.w. doses of turanose daily for 13 weeks. RESULTS: No signs of acute toxicity, including abnormal behavior, adverse effect, or mortality, were observed over the 14-day study period. In addition, no changes in body weight or food consumption were observed and the median lethal dose (LD50) for oral intake of turanose was determined to be greater than 10 g/kg b.w. General clinical behavior, changes in body weight and food consumption, absolute and relative organ weights, and mortality were not affected in any of the treatment group for 13 weeks. These doses also did not affect the macroscopic pathology, histology, hematology, and blood biochemical analysis of the mice examined. CONCLUSION: No toxicity was observed in the acute and 13-week subchronic oral toxicology studies that were conducted with ICR mice. Furthermore, the no-observed-adverse-effect level is greater than 7 g/kg/day for both male and female ICR mice.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.195-202
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• 2003

Chitosan is known to have antibacterial, antitumorogenic, hypolipidemic and immunopotentiating activities, hence finding diverse uses as a component in varying functional foodstuffs. However, some investigators reported it caused mineral absoiption inhibition and excess coagulation. From the chemical viewpoint, conventional chitosans are high-molecule polymers lacking water solubility, which could be related with their possible toxicity. A newly developed low- molecule water soluble chitosan is thought to have low toxicity compared to conventional chitosans. But no investigation was carried out to evaluate its toxicity. In this study, a 28-day subacute oral toxicity study of the water-soluble chitosan was performed in Sprague-Dawley rats of both sexes. Each 36 male and female rats were orally administered with 500, 1,000 and 2,000 mg/kg/day for 28 consecutive days, respectively. Clinical parameters (growth rate, feed and water consumption, daily inspection, urine analysis) during the 28 days indicated the water-soluble chitosan did not induce any abnonnal changes. There were no abnormal findings due to the administration of the test substance in gross and microscopic findings. We had not found alteration in absolute and relative organ weight between the control and treated groups, with only exception in the liver but lacking dose-dependency. The results of hematology and serum biochemistry examination revealed that no treatment related changes were between control and all dose groups. In conclusion, it was suggested that subacute toxicity of the water-soluble chitosan was low and the no-observed adverse effect level was considered to be over 2,000 mg/kg in rats.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.11 no.3
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• pp.198-205
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• 2001

Many reactive dyes have been used in occupational settings without knowing their toxicity and health hazard information. To investigate the toxicity of reactive dye, C.I.No. Reactive Red 195 was exposed to male and female Sprague Dawley rats by inhalation for 28 days. The rats were exposed C.I.No. Reactive Red 195 for 6 hrs per day and 5days per week. The concentrations for the inhalation exposure were 0, 10, 40 and $160mg/m^3$. After 4 weeks of exposure, rats were examined for exposure related changes through pathology, blood biochemistry and hematology. There were no dose related changes including clinical signs, body weight and relative organ weight changes, hematological and biochemical and histopathological findings. The results indicate that no observed adverse effect level (NOAEL) of 28 days inhalatrion toxicity test for C.I.No. Reactive Red 195 was $160mg/m^3$.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.251-261
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• 1993

The subacute toxicity of combined antibiotics, SP-102 (Sulbactam.Piperacilline), was examined in S.D.rats. Four groups of rats were administered intraperitoneally with 0, 512, 1280 and 3200 mg/kg/day of SP-102 for 30 days. Hain clinical sign related to the compound was soft stool. The body weight gain was slightly decreased in male rats treated with 1280, 3200 mg/kg and in female rats treated with 1280 mg/kg of SP-102. Water consumption was significantly increased in rats administered with SP-102. There were no dose-related changes of urinalysis, biochemical examination and hematological findings in all the groups treated with SP-102. Gross necropsy and histopathology revealed no evidence of specific toxicity related to SP-102. Our data indicate that no-observed effect level of SP-102 is below 512 mg/kg in male and female rats. Maximum tolerated dose of SP-102 was estimated to be above 3200 ma/kg in this study.

• Toxicological Research
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• v.11 no.1
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• pp.147-155
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• 1995

HRccine was administered subcutaneously for 4 weeks to rabbits at dose levels of 300, 60 and 12 times the expected clinical dose to evaluate the subacute toxicity. There were no effects in clinical signs, body weight changes, food consumption, water consumption, urinalysis and blood biochemistry in any animals tested. In hematological examinations, decrease of lymphocyte counts and increase of platelet counts were observed in the medium- and high-dose treated groups. Absolute weights of thymus were tending to decrease, but no pathological changes were observed in microscopic examinations. The no-effect dose in subacute toxicity study of rabbits was considered to be 300 times the expected clinical dose.