• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.120-120
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• 2002

This study was designed to evaluate a repeated intravenous toxicity of a novel cephalosporin antibiotic, IDC7181, in Beagle dogs. Four groups, each consisting of 3 male and 3 female dogs (one year old, body weight 8 - 10 kg), were intravenously administered with IDC7181 at dose levels of 0 (vehicle control), 10, 50 or 250 mg/kg/day, respectively, for 28 days.(omitted)

• Toxicological Research
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• v.20 no.4
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• pp.375-380
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• 2004

The toxicity of CKD-602 was investigated at doses of 0, 3, 9, and 27 mg/kg in rats, by administering the same total dose over 24-hr continuous infusion or bolus injection. CKD-602 treatment caused gastrointestinal symptoms such as diarrhea, soft stool, and soiled perineal region. It also decreased body weight at doses of 9 and 27 mg/kg in a dose-dependant manner. At 3 mg/ kg, clinical signs and body weight decrease were more severe in the infusion group than in the bolus group. In the bolus group, mortalities were 0/8, 0/8, 1/8, and 3/8 at 0, 3, 9, and 27 mg/kg, respectively, whereas those were 0/8, 1/8, 8/8, and 8/8 in the infusion group. $LD_{50}$ values were 36.25 mg/kg for bolus and 3.50 mg/kg for infusion, respectively. This finding indicates that the toxic potency of CKD-602 by continuous infusion is about 10 times higher than by bolus injection. Our findings suggest that the toxic effects of CKD-602 are dependant upon the duration of intravenous administration.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.170-170
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• 2001

This study was designed to evaluate a repeated intravenous dose toxicity of a new anticancer agent, SB extracted from Pulsatilla korean Nakai in Beagle dogs. Animals were intravenously injected with dosages of 0, 0.062, 0.25, and 1 mg/kg of SB everyday for 13 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumptions, opthalmoscopy, and urine analysis. There were somewhat significant differences compared with control group in organ weight, biochemical examination, and hematology findings of animals treated with SB. However, these changes were not dose-related changes. Gross and histopathological findings revealed no evidence of specific toxicity related to SB. These indicate that intraveous maximum tolerated dose value of SB may be over 1mg/kg in rats.

• Toxicological Research
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• v.12 no.2
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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.

• Journal of Pharmacopuncture
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• v.19 no.2
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• pp.155-162
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• 2016

Objectives: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single-dose test with sprague-dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. Results: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. Conclusion: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal.

• YAKHAK HOEJI
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• v.57 no.4
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• pp.282-288
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• 2013

Zinc oxide nanoparticles (ZnONPs) are widely used in a variety of products and cosmetic products including paper, paints, plastics and sunscreen. However, information on the safety of ZnONPs are not enough and many publications suggest possible toxic effects on environmental and human health. Furthermore, physico-chemical characteristics of nanoparticles makes it hard to test toxicity using the test guidelines of chemicals adopted by regulatory bodies. In this study, stability of ZnONPs was investigated using different types of isotonic solution, which is important in the toxicity study of intravenous route. Precipitation, aggregation, size, zeta potential and morphology of ZnONPs were evaluated with different times and concentrations. Precipitation of ZnONPs were observed in ionic isotonic solution including phosphate-buffered saline, Kreb's-Ringer solution, physiological salt solution and cell culture media of DMEM (Dulbecco's Modified Eagle's Medium) with 10% fetal bovine serum. On the other hand, they were stable without precipitation in non-ionic isotonic solution such as 5% glucose and 2% glycerol, respectively, which are biocompatible for intravenous injection. The average size of ZnONPs in 5% glucose and 2% glycerol was stably maintained, which is less than 30 nm and very similar as that in water dispersion of ZnONPs, provided by the manufacturer. The stability was maintained during the experimental period of 5 days and diluted state up to 15,000 ppm. These data suggest that 5% glucose and 2% glycerol solution can be used for the vehicles of ZnONPs in the toxicity study of intravenous injection route.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.42-50
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• 2015

Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

• 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.

• 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.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.74-79
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• 2012

Citrate-capped silver nanoparticles (AgNPs) are widely used in industry, consumer products and medical appliances. However, information on the toxicity, environmental fate and toxicokinetics are not enough. In this study, stability of citrate-capped AgNPs was investigated using different types of isotonic solution, which is important in the toxicokinetic study by the exposure route of intravenous injection. Size, morphology, zeta potential and ion formation were investigated in isotonic solutions for the physico-chemical characterization of AgNPs. Aggregation and precipitation of AgNPs were observed in saline or phosphate-buffered saline while they were stable without precipitation in 2% glycerol of isotonic solution. The average size of AgNPs in 2% glycerol was 6~10 nm, which was almost same as that in water-based suspension of AgNPs. Zeta potential was ranged from -30 mV to -60 mV, which was in the range of original stock AgNPs. The stability was maintained during the whole experimental period of 48 hours. Furthermore, the stability was not changed in different temperature (10~36$^{\circ}C$) and at different concentrations (10~1,000 ppm). The osmolarity of the AgNPs suspension was $299{\pm}1$ mOsm/kg which was in isotonic range. These data suggest that AgNPs in 2% glycerol solution can be used for the preparations of intravenous injection for toxicokinetic study without undesired disturbance of blood isotonicity.