• 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.

• Toxicological Research
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• v.11 no.2
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• pp.267-271
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• 1995

A single large dose of ethanol as well as chronic ethanol consumption produces alcoholic fatty liver in human and experimental animals. We examined the effects of YH439, a potential hepatoprotective agent, on alcoholic fatty liver generation in adult female rats. In rats treated with YH439 (250 mg/kg, po) 4 hr prior to a single dose of ethanol (6 g/kg, po), a significant decrease in hepatic triglyceride accumulation was observed. YH439 also has an inhibitory effect on hepatic triglyceride and cholesterol accumulation induced by repeated ethanol treatments for one week. Because it has been known that induction of alcoholic fatty liver is associated with lipid peroxidation and/or hepatic glutathione depression, the effect of YH439 on these parameters was determined in the livers of rats treated with ethanol. Coadministration with YH439 inhibited MDA formation and gIutathione depression induced by acute or repeated ethanol administration. In order to determine the effect of YH439 on ethanol metabolism in vivo, disappearance of ethanol from blood was measured. In rats treated with a single dose of ethanol (6 g/kg, po), the ethanol concentration in blood reached a peak approximately 120 min following the treatment which declined linearly for 18 hrs. YH439 had no effect on the decline of blood ethanol concentration regardless of the dose of ethanol given to rats. These results in this study suggest that YH439 has an inhibitory effect on fatty liver generation induced by acute or repeated ethanol consumption through a mechanism not directly related to the rate of ethanol metabolism in vivo.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.150-150
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.170-170
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.171-171
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• 2002

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.96-96
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• 2004

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.133-134
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• 2004

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.181.2-182
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• 2003

Single and 28-day repeated dose toxicity studies of botulinum toxin type A(BTA) were carried out in ICR mice and SD rats. respectively. In the single dose toxicity study. BTA was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89, 133 and 200 ng/kg. All animals died from 59 ng/kg. Some clinical signs were observed in most of both sexes from 59 ng/kg, but no signs were seen in all animals at 40 ng/kg. (omitted)

• Journal of The Korean Society of Clinical Toxicology
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• v.8 no.1
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• pp.1-6
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• 2010

Methylene blue is a very effective reducer of drug-induced methemoglobinemia. It has dose-dependent oxidation or reduction properties. In most cases, a dose of 1 to 2 mg/kg IV given over 5 minutes and immediately followed by a 15- to 30-mL fluid flush to minimize the local pain is both effective and relatively safe. The onset of action is quite rapid, and the effects are usually seen within 30 minutes. The dose may be repeated after 30 to 60 minutes and then every 2 to 4 hours as needed. The total dose should not exceed 7 mg/kg as a single dose or 15 mg/kg within 24 hours. Repeated treatment may be needed for treating compounds that have prolonged elimination or those compounds that undergo enterohepatic recirculation (e.g., dapsone). Methylene blue can cause dose-related toxicity. At high doses, methylene blue can also induce an acute hemolytic anemia and rebound methemoglobinemia. The reasons for treatment failure with methylene blue include ineffective GI decontamination, the existence of other forms of hemoglobin (e.g., sulfhemoglobin), a low or high dose of methylene blue and the toxicokinetics of some agents, such as aniline, benzocaine or dapsone.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.40-45
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• 2008

The objective of this study was to investigate the single dose and 2-week repeated dose toxicity of Aceporol 330 in ICR mice following single intravenous administration and to compare its toxicity with a commercially available solubilizer of paclitaxel, Cremophor EL. In single dose toxicity test, $LD_{50}$ of Aceporol 330 in mice was estimated to be greater than maximum applicable dose, 4 ml/kg. However, $LD_{50}$ of Cremophor EL in male mice was determined to be 4 ml/kg. Maximum tolerated dose (MTD) of males and females in Aceporol 330-treated group and MTD of females in Cremophor EL-treated group were 3 ml/kg. MTD of males in Cremophor EL-treated group was less than 3 ml/kg. Characteristic toxic symptoms, and hematological and blood chemical changes were not observed after single dose and repeated dose of Aceporol 330 or Cremophor EL. No histopathological abnormalities were found in organs of all animal groups. Based on the linear pharmacokinetic property of paclitaxel and the higher $LD_{50}$ in mice, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.