• Archives of Pharmacal Research
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• 제26권6호
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• pp.487-492
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• 2003

This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose ($LD_{50$}) and convulsant dose ($CD_{50}$) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher $CD_{50}.{\;}LD_{50}$ and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.

• 대한한방내과학회지
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• 제34권2호
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• pp.155-164
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• 2013

Objectives : This study aimed to evaluate the single oral dose toxicity of Jaeumganghwa-tang (Ziyinjianghuo-tang) and Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acidophyllus in male and female ICR mice. Methods : In this single oral toxicity study, non-fermented and fermented Jaeumganghwa-tang (Ziyinjianghuo-tang) were administered to male and female ICR mice as an oral dose of 500, 1000 and 2000 mg/kg. After single administration, body weight changes, general behavior, adverse effects and mortality were determined for 14 days. Serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There were no mortality or signs of toxicity for 14 days. There were also no significant differences in body weights, organ weights, or serum chemistry values between treatment and control groups. Conclusions : These results indicate that the 50% lethal dose of Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acipophullus may be over 2000 mg/kg. This finding can be expected to provide scientific evidence for the safety of Jaeumganghwa-tang (Ziyinjianghuo-tang) fermented with Lactobacillus acidophyllus.

• 동의생리병리학회지
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• 제27권4호
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• pp.453-459
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• 2013

The objective of this study was to evaluate the single oral dose toxicity of Polygalae Radix (PR) in male and female mice. PR extract (yield = 18.6%) was administered to ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). Animals were monitored for the mortality and the changes in body weight, clinical signs and gross observation during 14 days after dosing. Upon necropsy, organ weight and histopathology of 14 principal organs were examined. It was observed that there were no mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs related to PR extract up to 2,000 mg/kg. Therefore, 50% lethal dose ($LD_{50}$) and approximate LD of PR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg the limited dosages recommended by KFDA Guidelines, respectively.

• Toxicological Research
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• 제28권1호
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• pp.11-18
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• 2012

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

• 한국어병학회지
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• 제21권3호
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• pp.189-199
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• 2008

This paper aims to compare difference with the in an ability of their resistance and survival against in a non-specific defence mechanism of the olive flounder, between the virulent and the avirulent E. tarda strains. The tested E. tarda strains, we divided into the virulent and the avirulent strain groups on the basis of a value of 50% lethal dose (LD50) for the olive flounder weighed 10.3 g in average. The strains of LD50 101.6~104.2 cfu/fish were grouped as virulent strains, such as KE-1, KE-3, KE-5 and FSW910410. The group of avirulent strains as LD50 exceeded 108.7 cfu/fish were included the strains, SU100 and AL92448. A test was conducted to understand the survival ability of each strain in the mucus of the skin and the intestine of olive flounders. The results showed KE-1, KE-3, KE-5 and FSW910410 were highly to survive between 6 hours and 24 hours in intestine. The survival ability in the bile of olive flounder the number of avirulent strains declined during incubation but the virulent strain showed the number of alive bacteria having sustained or increased. In the test for the survival of bacteria in fresh sera of olive flounder, the virulent strains also had tendency to multiply. Concerning the tested bacteria internalization into the head kidney macrophages and the intracellurar replication in the macrophages of olive flounder. The virulent strains exhibited strong internalization, followed high rate replication. According to the results, virulent strains of E. tarda revealed more ability to resist and survive in the face of humoral and cellular defence factors than avirulent strains.

• 한국산업보건학회지
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• 제25권1호
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• pp.58-71
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• 2015

Objectives: The aims of this study were to investigate the classification system of chemical substances in the Occupational Safety and Health Act(OSHA) and Chemical Substances Control Act(CSCA) and to compare several health indices (i.e., Time Weighted Average (TWA), Lethal Dose ($LD_{50}$), and Lethal Concentration ($LC_{50}$) of chemical substances by categories in each law. Methods: The chemicals regulated by each law were classified by the specific categories provided in the respective law; seven categories for OSHA (chemicals with OELs, chemicals prohibited from manufacturing, etc., chemicals requiring approval, chemicals kept below permissible limits, chemicals requiring workplace monitoring, chemicals requiring special management, and chemicals requiring special heath diagnosis) and five categories from the CSCA(poisonous substances, permitted substances, restricted substances, prohibited substances, and substances requiring preparation for accidents). Information on physicochemical properties, health indices including CMR characteristics, $LD_{50}$ and $LD_{50}$ were searched from the homepages of the Korean Occupational and Safety Agency and the National Institute of Environmental Research, etc. Statistical analysis was conducted for comparison between TWA and health index for each category. Results: The number of chemicals based on CAS numbers was different from the numbers of series of chemicals listed in each law because of repeat listings due to different names (e.g., glycol monoethylether vs. 2-ethoxy ethanol) and grouping of different chemicals under the same serial number(i.e., five different benzidine-related chemicals were categorized under one serial number(06-4-13) as prohibited substances under the CSCA). A total of 722 chemicals and 995 chemicals were listed at the OSHA and its sub-regulations and CSCA and its sub-regulations, respectively. Among these, 36.8% based on OSHA chemicals and 26.7% based on CSCA chemicals were regulated simultaneously through both laws. The correlation coefficients between TWA and $LC_{50}$ and between TWA and $LD_{50}$, were 0.641 and 0.506, respectively. The geometric mean values of TWA calculated by each category in both laws have no tendency according to category. The patterns of cumulative graph for TWA, $LD_{50}$, $LC_{50}$ were similar to the chemicals regulated by OHSA and CCSA, but their median values were lower for CCSA regulated chemicals than OSHA regulated chemicals. The GM of carcinogenic chemicals under the OSHA was significantly lower than non-CMR chemicals($2.21mg/m^3$ vs $5.69mg/m^3$, p=0.006), while there was no significant difference in CSCA chemicals($0.85mg/m^3$ vs $1.04mg/m^3$, p=0.448). $LC_{50}$ showed no significant difference between carcinogens, mutagens, reproductive toxic chemicals and non-CMR chemicals in both laws' regulated chemicals, while there was a difference between carcinogens and non-CMR chemicals in $LD_{50}$ of the CSCA. Conclusions: This study found that there was no specific tendency or significant difference in health indicessuch TWA, $LD_{50}$ and $LC_{50}$ in subcategories of chemicals as classified by the Ministry of Labor and Employment and the Ministry of Environment. Considering the background and the purpose of each law, collaboration for harmonization in chemical categorizing and regulation is necessary.

• 대한한의학회지
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• 제32권1호
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• 방사선산업학회지
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• 제10권4호
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• pp.211-217
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• 2016

We examined damages from gamma-irradiaion and determined the optimal gamma-ray dose for mutation breeding in lentil (Lens culinaris L.) bean. Four individual lines (L-C, L-2, L-8 and L-9), that have remarkable adaptability in South Korea were gamma-irradiated at doses of 50, 70, 100, 200, 300, 400, and 500 Gy. The germination rate of seed decreased as the dose increased over 50 Gy in all lines. However, $LD_{50}$ and $RD_{50}$ were different among lines. The median lethal doses($LD_{50}$) were approximately 127 (L-C), 74 (L-2), 95 (L-8), and 144 (L-9) Gy. The median reduction doses($RD_{50}$) for plant height, number of leaves, root length, and flash weight were 156, 176, 150, and 180 Gy for L-C, 253, 198, 127, and 142 Gy for L-2, 188, 175, 200, and 190 Gy for L-8, and 162, 210, 224, and 184 for L-9, respectively. The growth characteristics of the $M_1$ generation decreased as the dose increased over 70 Gy. The optimal doses of gamma irradiation for mutation breeding of lentil were determined to be 70 Gy (L-2, L-8) and 100 Gy (L-C, L-9). We performed the comet assay to observe nuclear DNA damage induced by gamma-irradiation. In comet assay, a clear difference was identified over 100 Gy treatments. With increasing doses of gamma-ray in the range of 50 to 500 Gy, the rate of head DNA was decreased significantly from 97.5% to 81.6%. Tail length was consecutively increased from $1.9{\mu}m$ to $17.4{\mu}m$. Our result provides basic information for construction of mutant pools in lentils.

• 대한약침학회지
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• 제18권4호
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• pp.7-11
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• 2015

Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations $(SDs)={\pm}0.71$; however, clotting was observed in the control group 13.8 s, $SDs={\pm}0.52$. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The $LD_{50}$ of the crude BV was found to be $177.8{\mu}g/mouse$. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase $A_2(PLA_2)$ and melittin, and that can increase the blood clotting times in vitro.

• 한국균학회지
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• 제14권1호
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• pp.61-70
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• 1986

Sterigmatocystin bears a close structural relationship to aflatoxin $B_1$ and is a carcinogenic compound that has been shown to affect various species of experimental animals. Reaction and toxicity of sterigmatocystin in the artificial gastric juice were investigated. Sterigmatocystin was degraded in artificial gastric juice and extracted by the method of A.O.A.C. After cleaned up by silica gel column chromatography, this substance was detected and characterized by thin layer chromatography, UV, IR and mass spectra. It showed $R{\mathcal{f}}$ 0.4 and brick-red color by TLC. Especially, in the mass spectrum of it, fragment peak at m/e 327 was due to the loss of the $-CH_3$ and $-H_2O$, fragment peak at m/e 341 was due to the loss of the $H_2O$ and $-H^+$, and fragment peak at m/e 239 was due to the loss of the 2-chloro-tetrahydrofuran and methyl group from the parent molecule. Therefore, a degraded substance of sterigmatocystin reacted in artificial gastric juice (Sub. K) was estimated with additional formation of hydrochloric acid. In four-day-old chicken embryos, the mean lethal dose $(LD_{50})$ was $140\;{\mu}g/egg$, and 90 to 100% of the embryos were killed with 1 mg/egg. This $LD_{50}$ $140\;{\mu}g/egg$ compared with an $LD_{50}$ $14.69\;{\mu}g/egg$ for sterigmatocystin (acute toxicity) showed the substance to be much less toxic than sterigmatocystin.