• Title/Summary/Keyword: Acute Toxicity Test

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Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract of Wattakaka volubilis in Wistar Female Rats

  • Gopal, Velmani;Agrawal, Nitin;Mandal, Subhash C.
    • Journal of Pharmacopuncture
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    • v.17 no.3
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    • pp.7-15
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    • 2014
  • Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W.) volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from $100-1000{\mu}g/mL$ of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and ${\alpha}$-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract's administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis. Conclusion: These results suggest that petroleum ether extract of W. volubilis has a non-toxic effect in Wistar female rats.

Single Oral Toxicity Study on the Standardized Extract of Salvia miltiorrhiza (단삼 표준화시료의 급성독성에 관한 연구)

  • Chang, Bo-Yoon;Oh, Bo-Ram;Sohn, Dong-Hwan;Kim, Sung-Yeon
    • Korean Journal of Pharmacognosy
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    • v.39 no.4
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    • pp.352-356
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    • 2008
  • Acute toxicity of standardized extract of Salvia miltiorrhiza Bunge was examined using male and female ICR mice. Mice were treated with standardized extract the intragastrically at 5 mg/kg, 50 mg/kg, 500 mg/kg or 2,000 mg/kg and observed for two weeks. At the doses used, no mortality or abnormal clinical signs in animals were shown during at the observation period. Also there was no difference in net body weight gain, gross pathological findings at the terminal sacrifice among the groups mice treated with different doses of the test substance. The results suggested that acute oral toxicity of standardized extract of S. miltiorrhiza in mice is very low at the conditions employed in this study.

Acute and Subacute Toxicity Studies of l-Muscone in Rats (랫드에서 l-muscone의 급성독성 및 아급성독성시험 연구)

  • 오승민;연제덕;남혜윤;박대규;조명행;정규혁
    • Toxicological Research
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    • v.13 no.4
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    • pp.435-447
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    • 1997
  • l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

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Evaluation of Acute Toxicity of Pomace Schisandra chinensis Extracts Using SD-rats (SD-rats를 이용한 오미자박 추출물의 급성경구독성 평가)

  • Seokho, Kim;Bo Ra, Yoo;Young-Suk, Kim;Jong-Min, Lim;Bon-Hwa, Ku;Kyeong Tae, Kwak;Byeong Yeob, Jeon
    • Herbal Formula Science
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    • v.30 no.4
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    • pp.281-291
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    • 2022
  • Objectives : In this study, acute oral toxicity test of pomace Schisandra chinensis extracts was conducted in order to up-cycling to a high value-added industry using by-products discarded in the production process of Schisandra chinensis products and active ingredients such as dibenzocyclooctadiene lignans in Schisandra chinensis. Methods : Pomace Schisandra chinensis extracts were orally administered to SD-rats(female, n=3) without a control group according to the 'OECD guidelines'. After, mortality and clinical signs were observed, and the deceased animals were subjected to an autopsy. In addition, acute oral toxicity test was sequentially performed in step I (300 mg/kg), step II(300 mg/kg), step III(2,000 mg/kg), and step IV(2,000 mg/kg) according to the mortality. Results : There were no abnormalities caused by pomace Schisandra chinensis extracts in step I and step II. However, one animal each died in step III and step IV. In addition, clinical signs(salivation, decrease in food intake, prone position, decrease of locomotor activity, loss of locomotor activity, convulsion, hypothermia, lacrimation, staining around mouth, soiled perineal region, reddish urine, chromaturia, decrease of fecal volume, lying on side, blackish stool, no stool, compound-colored stool, refusal to feed, excitement, hypersensitivity, rigidity, dorsal position, etc.) were observed. But, no clinical signs were observed from 5th day, and experiment animals recovered completely. Conclusions : As a result of this study, pomace Schisandra chinensis extracts may exhibit acute toxicity at concentrations of 2,000 to 5,000 mg/kg, and the GHS classification was designated as 'Category 5'.

Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity

  • Hwang, Eun-Sun;Kim, Gun-Hee
    • Preventive Nutrition and Food Science
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    • v.18 no.2
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    • pp.111-116
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    • 2013
  • Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, ${\alpha}$-cadinol, camphene, pinocarvone, ${\beta}$-caryophyllene, 3-cyclohexen- 1-ol, and ${\gamma}$-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral single gavage administration of C. indicum flower oil. There were no mortality and clinical signs of toxicity at 2,000 mg/kg body weight/day of C. indicum flower oil throughout the 15 day period. Micronucleated erythrocyte cell counts for all treated groups were not significantly different between test and control groups. Levels of 15.63~500 ${\mu}g$ C. indicum flower oil/plate did not induce mutagenicity in S. Typhimurium and E. coli, with or without the introduction of a metabolic activation system. These results indicate that ingesting C. indicum flower oil produces no acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation.

Application of Neutral Red Uptake Assay Using EPC Cells as an Alternative to the Fish Acute Toxicity Test for Pesticide (어류급성독성시험 대체법으로서 잉어표피세포를 이용한 Neutral Red Uptake 분석법 적용)

  • Seo, Ji-Hyun;Park, June-Woo;Lee, Sung-Kyu;Kim, Woo-Keun
    • The Korean Journal of Pesticide Science
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    • v.18 no.1
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    • pp.8-13
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    • 2014
  • This study evaluated in vitro cytotoxicity of 5 pesticides, including 2 herbicides, 2 germicides, and an insecticide, as an alternative to the fish acute toxicity test. The in vitro cytotoxicity was tested using a neutral red uptake (NRU) assay with epithelioma papulosum cyprini (EPC) cells that originated from the epidermal tissue of Cyprinus carpio (common carp). An in vivo fish acute toxicity test was conducted according to OECD Test Guideline No. 203 using Aphyocypris chinensis (Chinese bleak), Oryzias latipes (Japanese medaka), and C. carpio. The results showed that the sensitivity of the cell viability assay for the pesticides was similar to the fish acute test in ranking order despite having approximately 10 times less absolute sensitivity. The $r^2$ correlation values were calculated as 0.38 (p = 0.26), 0.76 (p = 0.05) and 0.90 (p = 0.01) for A. chinensis, O. latipes, and C. carpio, respectively. These results suggested that the potential of EPC cell viability assay as an alternative to the fish acute toxicity test due to their good correlation and NRU assay is expected to serve as a useful tool for predicting acute fish lethality for pesticides if further studies with a large set of pesticides are conducted.

Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats

  • Rojas-Armas, Juan;Arroyo-Acevedo, Jorge;Ortiz-Sanchez, Manuel;Palomino-Pacheco, Miriam;Castro-Luna, Americo;Ramos-Cevallos, Norma;Justil-Guerrero, Hugo;Hilario-Vargas, Julio;Herrera-Calderon, Oscar
    • Toxicological Research
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    • v.35 no.3
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    • pp.225-232
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    • 2019
  • Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

Acute Toxicity of Heavy Metals, Tributyltin, Ammonia and Polycyclic Aromatic Hydrocarbons to Benthic Amphipod Grandidierella japonica

  • Lee, Jung-Suk;Lee, Kyu-Tae;Park, Gyung-Soo
    • Ocean Science Journal
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    • v.40 no.2
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    • pp.61-66
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    • 2005
  • Benthic amphipod, Grandidierella japonica widely inhabits the Korean coastal waters and is developed as a standard test species for sediment toxicity tests. We exposed G. japonica to various pollutants including 4 kinds of inorganic metals (Ag, Cd, Cu and Hg), tributyltin [TBT], ammonia and 7 polycyclic aromatic hydrocarbon (PAH) compounds (acenaphthene, chrysene, fluoranthene, fluorene, naphthalene, phenanthrene and pyrene) to estimate the no observed effect concentration (NOEC) and the median lethal concentration (LC50) of each pollutant during the 96-hour acute exposure. Among all tested pollutants, TBT was most toxic to G. japonica, and Rg was most toxic among inorganic metals. The toxicity of pyrene to G. japonica was greatest among PAH compounds, followed by fluoranthene, phenanathrene, acenaphthene, fluorene and naphthalene. The toxicity of PAH compounds was closely related to their physico-chemical characteristics such as $K_ow$ and water solubility. G. japonica responded adequately to pollutant concentrations and exposure durations, and the sensitivity of G. japonica to various inorganic and organic pollutants was generally comparable to other amphipods used as standard test species in ecotoxicological studies, indicating this species can be applied in the assessment of environments polluted by various harmful substances.

Application of simple and massive purification system of dsRNA in vivo for acute toxicity to Daphnia magna

  • CHOI, Wonkyun;LIM, Hye Song;KIM, Jin;RYU, Sung-Min;LEE, Jung Ro
    • Entomological Research
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    • v.48 no.6
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    • pp.533-539
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    • 2018
  • The RNA interference (RNAi) has been considered as an important genetic tool and applied to develop a new living modified (LM) crop trait which is an improvement of nutrient quality or pest management. The RNAi of DvSnf7 has been used for resistance to LM maize and the Western Corn Rootworm which is a major agricultural pest for the US Corn Belt. Most of the environmental risk assessments (ERA) of double strand RNA (dsRNA) have been performed using in vitro transcript products, and not in vivo expressed product. A large amount of dsRNA was required for the acute toxicity assay of water fleas. Therefore development of massive dsRNA purification techniques is critical. Daphnia, a freshwater microcrustacean, is a model organism for studying cellular and molecular mechanism involved in life history traits and ecotoxicology. In this study, we established the massive dsRNA purification method using Escherichia coli and implemented acute toxicity assays to Daphnia magna. As a result, the present RNase A and DNase I, dsRNA was efficiently purified without any special techniques or equipment. Even though purified dsRNA existed during the acute toxicity test, lethality or abnormal behavior were not observed in D. magna. These results indicated that GFP and DvSnf7 dsRNA were not significantly affected to D. magna due to their lack of sequence matching in its genome. The purification method of dsRNA and the acute toxicity assay of water fleas using purified dsRNA would be suitable for the toxicological studies of LMOs to aquatic non-target organisms.

Acute toxicity test and safety classification for Termitomyces albuminosus containing pharmacologically similar ingredient of Aconitum koreanum (백부자-대체 가능 한약재의 계종버섯에 대한 급성독성시험과 안전성등급화)

  • An, Minji;Park, Yeongchul
    • The Korea Journal of Herbology
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    • v.32 no.4
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    • pp.33-38
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    • 2017
  • Objectives : Termitomyces albuminosus (Berk.) Heim is one of the famous wild edible mushrooms in the southern part of China. It is known that Termitomyces albuminosus, like Aconitum koreanum used in Korean traditional medicine, contains a kind of cerebroside, termitomycesphin, causing a pharmacologic effect on the neuron system. The pharmacologic effect of Termitomyces albuminosus can be used to possibly replace Aconitum koreanum. However, It needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was conducted to obtain acute information of the toxicity of dried-Termitomyces albuminosus powder and to secure its safety in clinical applications. Methods : In order to calculate approximate lethal dose(ALD), test substance was orally administered to male and female SD-rat at dose levels of 5,000 and 0 (vehicle control) mg/kg (body weight). Based on the result of this toxicity, also the estimation of safety classification was calculated using the HED-based (human equivalent dose) MOS (margin of safety). Results : There were no mortalities, test substances treatment-related clinical signs, no changes in the body or organ weights, and no gross or histopathological findings at 14 days after treatment with test substance. Thus, the approximate lethal dose of dried-Termitomyces albuminosus powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the limit dose, 5000 mg/kg, it was estimated that dried-Termitomyces albuminosus powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.