• Title/Summary/Keyword: Acute toxicity study in mice

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Toxicity Assessment and Establishment Acceptable Daily Intake of Penthiopyrad (펜티오피라드(Penthiopyrad)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Hong, Soon-Sung;Park, Kyung-Hun;Kim, Chan-Sub;Park, Jae-Eup;Hong, Moo-Ki;Im, Moo-Hyeog;Kim, Young-Bum;Han, Bum-Seok;Han, Jeung-Sul
    • The Korean Journal of Pesticide Science
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    • v.14 no.4
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    • pp.478-489
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    • 2010
  • Penthiopyrad is a fungicide agent in types of pyrazole which is showing the effect of prevention in fungal disease and powdery mildew. In order to register this new pesticide, reports of acute toxicity and chronic toxicity by animal study were examined to set acceptable daily intake to evaluate hazards of consumers. Acute toxicity was low in toxic, and it did not have the effect of acute dermal toxicity, acute eye irritation, or skin sensitization. As the result of the study in chronic toxicity, the common effect of chemical appeared in the liver and thyroid which was proven as a toxic effect. Two-generation reproduction toxicity, genotoxicity, and prenatal development toxicity were not proven. As the result of carcinogenic study, increase of thyiroid follicular adenoma in the rat and the frequency of liver hepatocellar adenoma in mice were also increased. However, it was decided that the threshold value on the effect in chemicals could be controlled through study liver enzyme induction. Therefore, the ADI for penthiopyrad is 0.081 mg/kg/ bw/day, based on the NOAEL of 8.10 mg/kg bw/day of twelve-months dogs study and applying an uncertainty factor of 100.

The Characteristics of Antitumor Agent Isolated from Streptomyces sp.409 (Streptomyces sp.409 에서 분리한 항암활성 물질의 특징)

  • 장영수
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.478-487
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    • 2000
  • This study was carried out to find new anti-tumor agent producing microbe and to characterize the anti-tumor agent produced from the microbe. Purified compound that has a high cytotoxicity against tumor cell-lines could be obtained from the broth culture filtrates of Streptomyces sp.409 strain isolated from soil in Korea. The in vitro cytotoxicity the in vivo evaluation of acute toxicity the safety assessment of the anti-tumor compounds and the taxonomic characteristics of the anti-tumor agent were measured. The antitumor compound 1 and 2 were obtained from the broth culture filtrates of Streptomyces sp.409 strain. The cytotoxicity of the compound 1 against tumor cell-line P388D$_1$ showed almost 4.5 times higher than that of adriamycin. However in the cytotoxicity against normal cell line Vero E6, adriamycin showed adversely 4 times higher than the compound 1 ($IC_{50}$/ value: 228.7 $\mu\textrm{g}$/$m\ell$). In comparison study with compound 1 and compound 2 in the in vitro cytotoxin productivity against tumor cell lines, $IC_{50}$/ value of the compound 1 was 0.25 $\mu\textrm{g}$/$m\ell$ in tumor cell line P388D$_1$and 0.53 $\mu\textrm{g}$/$m\ell$ in tumor cell-line L1210, and that of the compound 2 was 7.18 $\mu\textrm{g}$/$m\ell$ and 35.71 $\mu\textrm{g}$/$m\ell$, respectively; LD$_{50}$ value of the compound 1 in the in vivo acute toxicity in mice was 22.62 $\mu\textrm{g}$/kg body weight. These results suggest that compound 1 purified from Streptomyces sp. 409 has anti-tumor activity and will be developed as an anti-tumor drug.g.

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Single-dose Oral Toxicity Study of β-glucosidase 1 (AtBG1) Protein Introduced into Genetically Modified Rapeseed (Brassica napus L.) (GM 유채에 도입된 β-glucosidase 1 (AtBG1)의 단회투여독성시험)

  • Lee, Soonbong;Jeong, Kwangju;Jang, Kyung-Min;Kim, Sung-Gun;Park, Jung-Ho;Kim, Shinje
    • Journal of Life Science
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    • v.27 no.2
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    • pp.194-201
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    • 2017
  • Rapeseed (Brassica napus L.) is an oil crop classified as Brassicaceae, and it is widely grown worldwide. To develop a drought-resistant rapeseed, the ${\beta}$-glucosidase 1 (AtBG1) gene was introduced into rapeseed because drought- and salt-resistance phenotypes were observed when the AtBG1 gene was overexpressed in arabidopsis. Newly developed genetically modified crop must be proved to be safe. Safety assessments are based on the historical usage and scientific reports of a crop. In this study, we examined the potential acute oral toxicity of AtBG1 protein expressed in genetically modified (GM) rapeseed and calculated the minimum lethal dose at 6 weeks in both male and female ICR mice. AtBG1 protein was fed at a dose of 2,000 mg/kg body weight in five male and five female mice according to the marginal capacity concentration of OECD, 2,000 mg/15 ml/kg. Mortalities, clinical findings, and body weight changes were monitored for 14 days after dosing, and postmortem necropsy was performed on day 14. This study showed that no deaths occurred in the test group, and AtBG1 protein did not result in variations in common symptoms, body weight, and postmortem findings between the two groups. This showed that the minimum lethal dose of AtBG1 protein expressed in transgenic rapeseed exceed 2,000 mg/kg body weight in both sexes.

Mouse Single Oral Dose Toxicity Test of Taraxaci Herba Aqueous Extracts (포공영(蒲公英) 추출물의 마우스 단회 경구투여 독성 실험)

  • Gu, Ja-Hwan;Kim, Se-Ran;Lee, Jin-Won;Park, Mee-Yeon;Choi, Hae-Yun;Kim, Jong-Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.4
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    • pp.650-657
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    • 2011
  • The object of this study was to obtain acute information (single oral dose toxicity) of Taraxaci Herba (Dried total parts of Taraxacum platycarpum. H.Dahlstedt (Compositae)), has been traditionally used in Korean medicine for treating various inflammatory diseases. In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 mg/kg according to the recommendation of Korea Food and Drug Administration Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after single oral treatment of Taraxaci Herba aqueous extracts according to KFDA Guidelines with organ weights and histopathological observations of 12 types of principle organs. After single oral treatment of Taraxaci Herba aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. Except for slight soft feces, which were detected in male mice treated with 2,000 mg/kg of Taraxaci Herba aqueous extracts at 1 day after end of treatment. The results obtained in this study suggest that the LD 50 and ALD of Taraxaci Herba aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg that was the highest dose recommended by KFDA and OECD. However, it also observed that the possibility of digestive disorders, like diarrhea when administered over 2,000 mg/kg of Taraxaci Herba aqueous extracts in the present study, but these possibilities of digestive disorders can be disregard in clinical use because they ate transient in the highest dosages male only.

Anxiolytic effect of leaf galls extracts of Pipernigrum Linn. in Swiss Albino mice

  • Rajesh, R;Sathiyanarayanan, L;Arulmozhi, S;Ruby, Ruby
    • Advances in Traditional Medicine
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    • v.9 no.2
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    • pp.142-148
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    • 2009
  • Anxiety disorders are one of the serious problems which need proper therapy devoid of side effects of presently available medicines. The present study evaluates the anxiolytic and sedative activity of leaf galls of Piper nigrum Linn. in Swiss Albino mice. The pet. ether, chloroform, ethyl acetate and ethanol extracts of leaf galls of Piper nigrum Linn were obtained by continuous soxhlet extraction. The prepared extracts were found to be safe up to 2000 mg/kg body weight of mice in the acute toxicity study. Each extract was assessed for anxiolytic activity in Swiss Albino mice by elevated plus Maze, open field test, rota rod test and phenobarbitone induced sleeping time test. In the Elevated Plus Maze test, the pet.ether extract and chloroform extract at a dose of 50 mg/kg b.w. orally, significantly (P < 0.01) increased the number of entries and time spent in open arm comparable with standard diazepam at the dose of 10 mg/kg. b.w. p.o. In the open field test, pet. ether extract (50 mg/kg b.w. p.o.) showed significant increase (P < 0.01) in ambulation and activity in the center. Chloroform extract (50 mg/kg b.w p.o.) was significant (P < 0.05) for both ambulation and center activity. Pet. ether extract (50 mg/kg b.w. p.o) also showed significant activity (P < 0.01) in rota rod test. All the results are comparable with standard diazepam at the dose of 1 mg /kg b.w, p.o. Moreover all the extracts showed significant (P < 0.01) increase in the phenobarbitone induced sleeping time among which pet.ether showed more prominent activity (36%) comparable with control. The results revealed that, the active pet.ether extract and chloroform extract of leaf galls of Piper nigrum Linn is worthwhile to develop the bioactive principle for anxiolytic activity.

Anti-nociceptive, Anti-inflammatory, Mental Effects of Essential Oil from Thymus magnus (섬백리향 정유의 진통, 항염증, 정신적인 작용)

  • Kim, Sun-Min;Suk, Kui-Duk
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.508-516
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    • 2007
  • Thymus magnus is an endemic (Ulleung Island) species in Korea. This plant is used as diaphoretics and carminatives in traditional medicine. In the literature, few scientific assays were realized on this species, such as antibiotic (Streptococcus pneumoniae, Staphylococcus aureus, Salmonella enteritidis, and S. typhimurium) and antifungal activities. In order to clarify whether essential oil of T. magnus have pharmacological effects, anti-inflammatory, sedative, anti-depressant, analgesic, and sleep-prolonged effects were investigated using animal models. From this study, the following conclusions were attained; 1) Essential oil of T. magnus did not show any acute toxicity on mice when orally administered at the dose of 2-3 g/kg body weight. 2) Essential oil of T. magnus possessed strong anti-inflammatory activity, similar to that of a positive control prednisolone. 3) Essential oil of T. magnus had excellent analgesic activity, comparable to that of aspirin. 4) The essential oil of T. magnus possessed strong sleep-prolonged effect on pentobarbital induced-sleep test in mice model. 5) In the hot plate test, the essential oil of T. magnus had moderate effect. 6) And the essential oil of T. magnus had no significant effects in forced-swimming test and open-field test.

The Influence of Methanol Extract of Ulmus davidiana var. japonica Cortex on Gastric Erosion and Ulcer and Paw Edema in Rats (느릅나무 수피 엑스가 흰쥐의 위염, 위궤양 및 발부종에 미치는 영향)

  • 이은방;김옥경;정춘식;정기화
    • YAKHAK HOEJI
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    • v.39 no.6
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    • pp.671-675
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    • 1995
  • The bark of Ulmus davidiana var. japonica(Ulmaceae) has been described in traditional books to have diuretic and laxative actions, to ameliorate edematous disease, and to be used in insomnia and gastointestinal disorders. Thus this study was carried out to elucidate some of the pharmacological activities of the plant extracts. The results obtained in tills experiment indicated that its methanol extract elicited remarkable inhibition of HCI.ethanol induced gastric lesion, Shay ulceration and gastric secretion. However, it showed no anti-inflammatory action. The acute toxicity of the extract was low, that is, the minimum lethal dose was more than 2000 mg/kg by oral administration in mice. The systematic fractionation of the methanol extract by hexane, ether, ethylacetate and butanol resulted in potent prevention of gastric erosion in butanol and water fractions.

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Allergenicity and toxicity evaluation of the PAT protein expressed in herbicide-tolerant genetically modified Zoysia japonica (제초제저항성 GM 잔디에서 발현된 PAT 단백질의 알레르겐 유발 가능성 및 독성 평가)

  • Jeong, Hye-Rin;Sun, Hyeon-Jin;Kang, Ji-Nam;Kang, Hong-Gyu;Lee, Hyo-Yeon
    • Journal of Plant Biotechnology
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    • v.47 no.4
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    • pp.316-323
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    • 2020
  • This study aimed to evaluate the potential allergenicity and oral toxicity of the phosphinothricin acetyltransferase (PAT) protein expressed in Zoysia japonica, a herbicide-tolerant genetically modified (GM) zoysiagrass. In silico analysis of PAT showed no similarities with any known allergenic or toxic proteins, with <35% amino acid sequence homology with known allergens across a length of 80 amino acids and no continuous eight amino acid identity with known allergens. The PAT protein expressed in Z. japonica degraded very rapidly in the simulated gastric fluid in the presence of pepsin, and, no glycosylation of PAT was observed. The oral toxicity test revealed no mortality or toxic effect in mice following PAT administration at 4,000 mg/kg body weight. Our findings indicate that the PAT protein expressed in Zoysia japonica does not exhibit allergenic or toxic properties.

Toxicogenomics Analysis on Thioacetamide-induced Hepatotoxicity in Mice

  • Lim, Jung-Sun;Jeong, Sun-Young;Hwang, Ji-Yoon;Park, Han-Jin;Cho, Jae-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.2 no.2
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    • pp.126-133
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    • 2006
  • Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

The Acute Toxicity of Novel Platinum(II) Complexes

  • Roh, Young-Soo;Lee, Kyung-Tae;Jung, Sae-Young;Jung, Jee-Chang;Chang, Sung-Goo;Park, Byung-Gi;Cho, Dae-Hyun;Kim, Jun-Gyou
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.120-120
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    • 1995
  • This study was conducted to examine novel Pt(II) complexes, (KHPC-002; [Pt(trans-1-dach) (DPPE)]. 2NO$_3$, KHPC-005;[Pt(cis-1-dach)(DPPP)]. 2NO$_3$ and KHPC-006; [Pt(cis-1-dach) (DPPE)]. 2NO$_3$) for their acute toxicities and toxicological profiles in preclinical studies. In male and female mice given a single intraperitoneal administration of KHPC-002, KHPC-005 and LHPC-006, we determined that LD$\_$50/ values of pt(II) complexes were 295.5mg/kg(M), 350.4mg/kg(F);KHPC-002, 158.7mg/kg(M), 157.7mg/kg(F); KHPC-005, 574.8mg/kg(M), 596.5 mg/kg (F); KHPC-006, respectively. In gross and histopathological examination on dead animals, no abnormal changes were observed in any organs.

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