• Toxicological Research
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• v.27 no.3
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• pp.133-135
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• 2011

The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected in the final reports are mainly due to the followings; 1) Inaccurate description or use of NOEL, NOAEL and LOAEL, 2) Insufficient and inappropriate interpretations in findings from toxicity test. This paper is intended to provide the insight into distinguishing NOAEL from NOEL and LOAEL, and into classifying findings from toxicity test. Here, the three step method is newly suggested by applying the weight-based classification to the NOEL, NOAEL and LOAEL based on the findings.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.287.3-288
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• 2002

Previously. we reported a novel polymeric micellar solubilizeI'. Aceporol 330. that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study. we have developed a new micellar solubilizeI, Aceporol 460. that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. (omitted)

• Journal of Pharmacopuncture
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• v.1 no.1
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• pp.103-125
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• 1997

In order to study of safety, Hwanggum(黃芩) aqua-acupuncture was prepared by boiling extract and filtration. This study was performed to determine the toxic effects of graded dose levels and effects of Scutellaria Root after repeated administration(14days). From these results, Hwanggum(黃芩) aqua-acupuncture was quite sag in male and female rats.

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.232-238
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• 1996

The physical dependence potency of DA-5018, a non-narcotic analgesic agent, was tested in mice dosed with 0.5 and 4 mg/kg/day for 2 months and daily increasing doses of 1, 2, 4, 6, 8 and 10 mg/kg over 10 days. Physical dependence was assessed taking natural withdrawal induced morphine-type abstinence (jumping, falling, biting or backward locomotion, rearing etc.) as well as barbiturates-type abstinence (body weight reduction, convulsion, ataxia etc.) into consideration. The results were compared with those after the same daily increasing doses of morphine. DA-5018 did not show evidence of physical dependence liability or abuse potential as measured by morphine-type or barbiturate-type abstinence signs following daily increasing or 2-month repeated administration. On the other hand, daily increasing doses of morphine produced physical dependence and the dependent state disappeared about 6 hours after the start of withdrawal signs. In the single dose suppression test, a single dose of morphine completely suppressed natural withdrawal signs that appeared in morphine-dependent animals. Therefore, these results indicate that DA-5018 does not have abuse potential and physical dependence liability.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.05a
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• pp.54-54
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• 2003

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2007.11a
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• pp.227.1-227.1
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• 2007

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.139-139
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• 2005

• 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.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.449-455
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• 1996

Betaine is one of the major water-soluble components in Lycii Fructus. In the present study the effect of repeated betaine treatment on the hepatotoxicity and the cytochrome P-4 50-dependent enzyme system was examined in adult female rats. Administrations of betaine (100 or 1,000mg/kg/day, ip) to rats repeatedly for 4 or 9 days did not evoke hepatotoxic response as determined by increases in glutamic pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT) activities measured 24 hours following the final dose of betaine. The activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and p-nitrophenol hydroxylase as well as the contents of cytochrome P-450 were determined in hepatic microsomes of rats treated with betaine(1,000mg/kg/day, ip) for 4 or 9 days. Repeated treatment of rats with betaine for a period of 4 days induced a marginal decrease in the contents of cytochrome P-450, but did not influence the activities of p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, or aminopyrine N-demethylase. Extension of the betaine treatment to 9 consecutive days failed to alter the parameters for hepatic drug metabolizing activity determined in the present study. Since repeated large doses of betaine were demonstrated to be tolerated by rats without showing any toxicity or changes in drug metabolizing enzyme activities in the liver, this compound appears to be relatively safe to animals upon long-term ingestion.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.418-424
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• 2012

Repeated stress induces corticosterone release. However, it is not clear that stress results in further elevation of corticosterone levels, and the roles of released corticosterone to aggravate stress-related symptoms are also not clear. This study investigated whether neuronal modulation was induced in the amygdala after two kinds of stress, that is, such as electric shock and corticosterone injection. It was found that stress by electric shock decreased the expression of tyrosine hydoroxylase (TH) in the amygdala while the expression of pERK was increased. However, there is no difference in the expressions of TH and pERK in the frontal cortex compared with those of the control group. The level of corticosterone was significantly increased in the serum after stress. To determine the effect of corticosterone on the induction of anxiety and the expression of TH, the rats received corticosterone (20 mg or 40 mg/kg i.p.) for 1 day, 1 week, 2 weeks and 3 weeks, respectively. The spent time in open arms of the EPM (elevated plus maze) test was significantly decreased after 1 week, 2 weeks and 3 weeks. The time spent in open arms of the EPM test after repeated injections of corticosterone was significantly decreased in a dose-dependent manner. The expression of TH in the amygdala was reduced after following repeated corticosterone treatment for 2 weeks and 3 weeks. Collectively, this study suggests that corticosterone has a major role in the induction of anxiety and the modulation of TH expression, at least, in the amygdala.