• Title/Summary/Keyword: 50% lethal dose

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Acute Toxicity Study of the 2-butoxyethanol by Intratracheal Instillation in Male Sprague-Dawley Rats (수컷 랫드(Sprague-Dawley)에서 2-부톡시에탄올(2-butoxyethanol)의 단회 기도내 투여에 따른 급성 독성시험)

  • Kim, Hyeon-Young;Kim, In-Hyeon;Kim, Min-Seok;Kim, Sung-Hwan;Lee, Kyuhong
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.31 no.4
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    • pp.473-483
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    • 2021
  • Objectives: The present study aimed to evaluate the potential toxicity of 2-butoxyethanol after intratracheal instillation in male rats. Methods: In order to calculate median lethal dose (LD50) of 2-butoxyethanol using Probit analysis with SAS program, the 2-butoxyethanol was administered with dose levels of 0, 101.64, 203.28 and 406.56 mg/kg by once intratracheal instillation to male rats. During the test period, clinical signs, mortality, body weights, organ weights, hematology, and serum biochemistry were examined. At the end of 14 days observation period, all animals were sacrificed and gross finding and histopathological examination were performed. Results: All animals of 406.56 mg/kg group died within 2 weeks after the administration of 2-butoxyethanol. Treatment-related clinical signs, gross observation and histopathological changes (mucous cell hyperplasia, alveolar macrophage aggregation, and hemorrhage) of lung exhibited an increased in 2-butoxyethanol treated groups in a dose dependent manner. However, there were no changes in the organ weights, hematology and serum biochemistry, and histopathology of any other organ except lung. Conclusions: On the basis of the results, it was concluded that a single intratracheal instillation of 2-butoxyethanol in male Sprague-Dawley rats resulted in some adverse effects on mortality, clinical sign, and histopathology in the lung. In the experimental conditions, the LD50 of 2-butoxyethanol was considered to be 287.2 mg/kg and lung was founded to be the target organ of 2-butoxyethanol.

Subchronic Oral Dose Toxicity Study of Enterococcus Faecalis 2001 (EF 2001) in Mice

  • Gu, Yeun-Hwa;Yamasita, Takenori;Kang, Ki-Mun
    • Toxicological Research
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    • v.34 no.1
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    • pp.55-63
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    • 2018
  • As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

Single Dose Oral Toxicity and Genotoxicological Safety Study of Ssanghwa-tang Fermented with Lactobacillus acidophyllus (유산균 발효 쌍화탕에 대한 단회 투여 경구 독성 및 유전 독성 연구)

  • Chung, Tae-Ho;Shim, Ki-Shuk;Kim, Dong-Seon;Lee, Jae-Hoon;Ma, Jin-Yeul
    • The Journal of Korean Medicine
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    • v.32 no.1
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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.

The Attenuation Mechanism and Live Vaccine Potential of a Low-Virulence Edwardsiella ictaluri Strain Obtained by Rifampicin Passaging Culture

  • Shuyi Wang;Jingwen Hao;Jicheng Yang;Qianqian Zhang;Aihua Li
    • Journal of Microbiology and Biotechnology
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    • v.33 no.2
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    • pp.167-179
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    • 2023
  • The rifampicin-resistant strain E9-302 of Edwardsiella ictaluri strain 669 (WT) was generated by continuous passage on BHI agar plates containing increasing concentrations of rifampicin. E9-302 was attenuated significantly by 119 times to zebrafish Danio rerio compared to WT in terms of the 50% lethal dose (LD50). Zebrafish vaccinated with E9-302 via intraperitoneal (IP) injection at a dose of 1 × 103 CFU/fish had relative percentage survival (RPS) rates of 85.7% when challenged with wild-type E. ictaluri via IP 14 days post-vaccination (dpv). After 14 days of primary vaccination with E9-302 via immersion (IM) at a dose of 4 × 107 CFU/ml, a booster IM vaccination with E9-302 at a dose of 2 × 107 CFU/ml exhibited 65.2% RPS against challenge with wild-type E. ictaluri via IP 7 days later. These results indicated that the rifampicin-resistant attenuated strain E9-302 had potential as a live vaccine against E. ictaluri infection. A previously unreported amino acid site change at position 142 of the RNA polymerase (RNAP) β subunit encoded by the gene rpoB associated with rifampicin resistance was identified. Analysis of the whole-genome sequencing results revealed multiple missense mutations in the virulence-related genes esrB and sspH2 in E9-302 compared with WT, and a 189 bp mismatch in one gene, whose coding product was highly homologous to glycosyltransferase family 39 protein. This study preliminarily explored the molecular mechanism underlying the virulence attenuation of rifampicin-resistant strain E9-302 and provided a new target for the subsequent study of the pathogenic mechanism of E. ictaluri.

Proton Beam Sensitivity of Basidiospore and Mycelium in Pleurotus ostreatus (느타리버섯 포자와 균사체의 양성자 빔 조사에 대한 민감도)

  • Kwon, Hye-Jin;Kong, Won-Sik
    • The Korean Journal of Mycology
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    • v.34 no.1
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    • pp.34-38
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    • 2006
  • To assess the effects of proton beam on radiation sensitivity of the basidiospore and mycelium of oyster mushroom (Pleurotus ostreatus), the $D_{10}$ values and $L_{50}$ (lethal 50%) values were analysed. By the proton beam radiation, the survival rate and germination rates increased at the dose of $10\;Gy{\sim}100\;Gy$ and then decreased significantly over 500 Gy. $L_{50}$ values of basidiospore and mycelium of Pleurotus ostreatus were over 500 Gy and 400 Gy, respectively. $D_{10}$ values were calculated from linear regression formulae ($D_{10}\;=\;-1/slope(b)$, y = a + bx) as 750 Gy and 1,250 Gy, respectively. Based on our experiment, the optimum dose of proton beam as a mutation source would be between from 500 Gy to 750 Gy for basidiospores and from 400 Gy to 1000 Gy for mycelium of oyster mushroom.

Single dose toxicity study of Jengjengamiyjintang in rats (정전가미이진탕(正傳加味二陳湯)의 랫드에서의 단회투여독성시험(單回投與毒性試驗))

  • Kim Sang-Chan;Kwon Young-Kyu;Byun Jun-Seok;Kim Han-Kyun;Byun Sung-Hui
    • Herbal Formula Science
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    • v.10 no.2
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    • pp.73-83
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    • 2002
  • The single dose toxicity of Jengjengamiyjintang, a herbal drug for duodenal ulcer was evaluated in male and female Sprague-Dawley (SD) rats. Jengjengamiyjintang was once administered to both sexes of rats at the dose levels of 2000, 1000, 500, 250 and 125mg/kg for oral route according to KFDA guidelines for single dose toxicity test (1999-61). In addition, vehicle control group was added in order to compare clinical signs, body weight changes and abnormal necropsy findings. After single administration, clinical signs were observed every twice a day for 14 days and body weights were measured 5 times including initial measurement on day 0. When observation period was over, the animals were sacrificed and macroscopic examination of major organs was conducted. Neither significant clinical signs nor death after administration was observed during the observation periods except for soft feces or diarrhea that were restricted to Day 1 of 2000 and 1000mg/kg-dosing groups. Although some accidental findings such as gross and histopathological changes of lung that were demonstrated in some animals of all experimental groups including vehicle control group, no abnormal necropsy findings and changes of body weight were observed at terminal necropsy in both sexes. From these results, it is considered that $LD_{50}$ of Jengjengamiyjintang is over 2000mg/kg in oral administration in both sexes of rats and approximated lethal dose was considered over 2000mg/kg.

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Effect of Sublethal Doses of Imidacloprid on the Green Peach Aphid, Myzus persicae (Imidacloprid의 아치사량이 복숭아혹진딧물의 생물적 특성에 미치는 영향)

  • Choi, Byeong-Ryeol;Lee, Si-Woo;Song, Yoo-Han;Yoo, Jai-Ki;Chung, Bu-Keun
    • The Korean Journal of Pesticide Science
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    • v.9 no.4
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    • pp.374-379
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    • 2005
  • Sublethal dose effect of imidacloprid on green peach aphid (Myzus persicae) was investigated. Nymphs of green peach aphid newly produced were counted on 4 days after sub-lethal dose treatment of imidacloprid. Numbers of nymph were not significantly different between $LC_1$ treatment and untreated control. Their numbers of nymph were 8.8 and 12.7 at $LC_1$ and untreated control, respectively. When they were tented at $LC_{10}$, $LC_{30}$ and $LC_{50}$. their numbers of newly produced nymph were 6.0, 5.1 and 3.9 and reduction rates were 52.7%, 59.8% and 69.3% at each treatment compare to untreated control. Reduction rates of newly laid nymph were proportional to the concentrations of imidacloprid treated. Repellent effect of aphid to imidacloprid was bigger in dipping than in watering method. Secretion amount had negative correlation with imidacloprid concentration in dipping method and suppression of secretion went up to 96%. In watering method, amount of secretion did not show any difference between insecticide concentration, but suppression, compared to untreated control, was over 97%.

Radiosensitivity of Lentil Bean (Lens culinaris L.) to Gamma-irradiation (감마선 조사가 렌틸(Lens culinaris L.)의 감수성에 미치는 영향)

  • Lee, Min-kyu;Ryu, Jaihyunk;Jeong, Sang Wook;Kim, Jin-Baek;Kang, Si-Yong;Kwon, Soon-Jae
    • Journal of Radiation Industry
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    • v.10 no.4
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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.

Changes in Glucose Concentrations and Activities of Cholinesterase in Serum, Brain and Spinal cord in Mice following Orally Administration of Parathion (Parathion을 경구투여한 Mouse의 체내 Cholinesterase 활성도 및 Glucose함량 조사)

  • 도재철;이창우;차우양;손재권;정종식
    • Korean Journal of Veterinary Service
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    • v.15 no.1
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    • pp.58-66
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    • 1992
  • The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

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The Influences of Extremely Low Frequency Magnetic Fields on Drug-Induced Convulsion in Mouse

  • Sung, Ji-Hyun;Jeong, Ji-Hoon;Kim, Jeong-Soo;Choi, Tai-Sik;Park, Joon-Hong;Kang, Hee-Yun;Kim, Young-Sil;Kim, Dong-Suk;Sohn, Uy-Dong
    • Archives of Pharmacal Research
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    • v.26 no.6
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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.