• Title/Summary/Keyword: ACUTE TOXICITY

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Effects of Acute Acid Stress on Hatching and Mortality of Hermaphroditic Teleost, Rivulus marmoratus(Cyprinodontiformes; Rivulidae)

  • Kim, Ae-Ri;Lee, Meoung-Sook;Park, Eun-Ho
    • Animal cells and systems
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    • v.7 no.4
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    • pp.345-348
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    • 2003
  • The effects of acute acid stress on hatching success and hatching period of laboratory-reared hermaphroditic fish Rivulus marmoratus were examined. The effects of acute acid toxicity on mortality was also determined in three life stages of this fish. There was a significant negative effect of acid stress on hatching performance in the R. marmoratus embryos. The hatching success was only 5% at pH 3.5 compared to over 78% at pH higher than 4.0. The hatching period was also delayed by low pH treatments. The larval and juvenile stages were more sensitive to acid toxicity on mortality than the adult stage, but larvae and juveniles showed similar sensitivity. The 96-h LC50 value was pH 3.8 in larval and juvenile stages and pH 3.3 in adult stage.

Thirteen-week repeated-dose oral toxicity study of the Modified Wenpitang-Hab-Wulingsan (WHW$^{(R)}$) in Sprague-Dawley rats (WHW$^{(R)}$의 랫드에서의 반복경구투여 독성에 관한 연구)

  • Oh, Tae-Woo;Sang, Bae-Hyo;Yoon, Cheol-Ho;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.43-51
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    • 2010
  • Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

Single and 13-week Repeated Dose Toxicity Study of DA-3002, An Authentic Recombinant Human Growth Hormone (천연형 인성장호르몬 DA-3002의 단회 및 13주 반복투여독성연구)

  • 김옥진;강경구;안병옥;백남기;이순복;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.161-172
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    • 1994
  • This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

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Comparison of Short-Term Toxicity Tests Based on Feeding Behavior and Temperature Control by Ceriodaphnia dubia (Ceriodaphnia dubia의 먹이섭생 기작과 온도조절에 근거한 급성독성조사법의 비교)

  • Park, Jong-Ho;Lee, Sang-Ill;Cho, Young-Oak
    • Journal of Korean Society on Water Environment
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    • v.20 no.1
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    • pp.48-54
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    • 2004
  • Two methods, a Ceriodaphnia algal uptake suppression test (CAUST) and a new toxicity test based on temperature control (TTBTC) which are based on feeding behaviour and temperature control, respectively, were developed and compared for the adoption as the better methodology for short-term toxicity screening. As previously published by Lee et aI., (1997), the CAUST method is based on the feeding behaviour of C. dubia and requires as little as 1 hour of contact time between C. dubia neonates and toxicant. However, even though CAUST requires only 1 hour of contact time, this method still take many hours for the preparation and measurement. Before the test starts, neonate digestive tracts were cleared by feeding yeast to the daphnids, Neonates were then exposed to toxicant, followed by addition of Scenedesmus subspiatus into the bioassay vessels. Daphnids were examined under the bright-field microscope with the presence of algae (indicated by a green colored digestive tract) or the absence of algae. Uptake indicated no toxic effect, whereas, absence of uptake indicated toxic inhibition. Unlike CAUST, the newly developed method (TTBTC) is based on just temperature control for the toxicity test of C. dubia. Initially, neonates are exposed to toxicants while the temperature of water bath containing media increased to $35.5^{\circ}C$. After 1.25 hour of contact time, the number of the daphnids, either live (no toxic effect) or dead (toxic effect), is counted without the aid of any instrument. In both methods, median effective concentrations ($EC_{50}$ values) were computed based on the results over a range of dosed toxicant concentrations. It showed that TTBTC was as sensitive as the standard 48-hour acute bioassay and CAUST. TTBTC and CAUST were much more sensitive than the I-hour I.Q. test and 30-minute Microtox. This study indicates that TTBTC is an easier and more rapid toxicity test than the standard 48-hour acute bioassay and even CAUST.

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.

Toxicological Evaluation of Phytochemical Characterized Aqueous Extract of Wild Dried Lentinus squarrosulus (Mont.) Mushroom in Rats

  • Ugbogu, Eziuche Amadike;Akubugwo, Iroha Emmanuel;Ude, Victor Chibueze;Gilbert, James;Ekeanyanwu, Blessing
    • Toxicological Research
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    • v.35 no.2
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    • pp.181-190
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    • 2019
  • Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

Single Oral Dose Toxicity Test of Fermented Samchulgeonbi-tang Extract in ICR mice (ICR 마우스를 이용한 발효삼출건비탕의 단회투여 독성에 대한 연구)

  • Jung, Young Pil;Yim, Nam-Hui;Kim, Aeyung;Hwang, Youn-Hwan;Park, Hwayong;Ma, Jin Yeul
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.61-65
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    • 2013
  • Objectives : Samchulgeonbi-tang (shenzhujianpi-tang) has been prescribed as one of traditional herbal medicine for treatment of stomach diseases since ancient time in Korea. Samchulgeonbi-tang extract was fermented by Lactobacillus spp. for improving the effect. However, the toxicity and safety of fermented Samchulgeonbi-tang (FS) extract were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of FS extract. Methods : To evaluate the acute toxicity and safety of FS extract, several doses of FS extract, 0, 500, 1000 and 2000 mg/kg, were orally administered to 20 male and 20 female ICR mice, respectively. After treatment with FS extract, we observed mortality, general toxicity, behavior and change of body weight for the 14 days. After 14 days of oral administration, all mice were sacrificed and hematological parameters were analyzed from blood serum. Results : In present study, the toxic signs such as mortality or abnormal behaviors by FS extract were not observed. There are no significant differences between FS-treated group and control group in body weight, organ weights, and hematological parameters. Conclusions : The remarkable adverse effects by FS extract were not observed in ICR mice. Also, any death was not occurred at all treated FS doses, 500, 1000 and 2000 mg/kg. Therefore, the approximate lethal dose (ALD) of FS extract may be more than 2000 mg/kg.

Acute Toxicity and Four-week Intravenous Toxicity Studies of Intralipidos (Intralipidos에 대한 급성독성 및 4주간 정맥 내 반복투여 독성시험)

  • Li, Guang-Xun;Che, Jeong-Hwan;Kang, Byeong-Cheol;Lee, Won-Woo;Ihm, Jong-Hee;Jung, Ji-Yun;Yi, Beoung-Hi;Nam, Jeong-Seok;Park, Jae-Hak;Lee, Yong-Soon
    • Toxicological Research
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    • v.14 no.3
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    • pp.443-452
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    • 1998
  • This sutdy was carried out to investigate the acute toxicity and foru-week intravenous toxicity of the intralipidos in rats and rabbits. The acute toxicity study of Intralipidos was performed in Spragur-Dawley (SD) rats. Intralipidos was administered by intravenous to maximum dose 200 ml/kg. $LD_{50}$ of intralipidos was found 139.5ml/kg and 153.8ml/kg in male female SD rats. Four-week toxicity of intralipidos using New Zealand White Rabbit and SD rats. The Rabbit and Rats were administered by intravenous seven days per week for 28 days, with dosage of 15, 6, 2 ml/kg/day and 20, 6, 2ml/kg/day, respectively. Animals treated with intralipidos did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. They were not significantly different from the control group in urinalysis, ocular examination hematological, serum biochemical value and histopathological examination. Therefore, Intralipidos was not indicated to have any toxic effect in the Rabbits and Rats, when it was administrated by intravenous below the dosage 15ml/kg/day and 20 ml/kg/day for four weeks.

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