• Title/Summary/Keyword: Sub-chronic toxicity

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Ecotoxicity Evaluation of PFCs using Marine Invertebrate, Sea Urchin (Mesocentrotus nudus) (둥근성게(Mesocentrotus nudus)를 이용한 과불화화합물의 생태독성평가)

  • Choi, Hoon;Lee, Ju-Wook;Lee, Seung-Min;Jeon, Hyung-Ju;Heo, Seung;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.80-87
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    • 2021
  • In this study, the toxic effects of PFOA and PFOS potassium salt on Mesocentrotus nudus using 10 min-fertilization rate and 48 h-normal embryogenesis were confirmed through the calculation of toxicity values such as Non-observed effective concentration, Low-observed effective concentration, and 50% of effective concentration. The case of 10 min-fertilization rate and 48 h-normal embryogenesis showed the concentration-dependent reduction pattern when exposed to PFOA and PFOS potassium salt, in tested concentration, respectively. The EC50 values of 10 min-fertilization rates for PFOA and PFOS potassium salt were 1346.43 mg/l and 536.18 mg/l, respectively, and the EC50 values of 48 h-normal embryogenesis were 42.67 mg/l and 17.81 mg/l, respectively. Both toxicity test methods showed high toxicity sensitivity to PFOS potassium salt. Recent studies have shown that the concentration of PFOA and PFOS in the marine environment has continuously decreased, and it is not enough to show acute toxicity to sea urchin. However, PFOA and PFOS have a very long half-life and can accumulate throughout the life of marine life, so it is still observed at a high concentration in shellfish. Therefore, a study on chronic toxicity through the whole-life cycle of marine organisms in coastal environments should be needed.

LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice

  • Boo, Hye-Jin;Park, So Jung;Noh, Myungkyung;Min, Hye-Young;Jeong, Lak Shin;Lee, Ho-Young
    • Biomolecules & Therapeutics
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    • v.28 no.3
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    • pp.250-258
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    • 2020
  • Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A3 receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A3 receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

Chronic Toxicity of a Combined Preparation of Ticlopidine and Ginkgo Biloba Extract (EGb 761) Orally Administered to Rats for 13 Consecutive Weeks

  • Kim, Sang K.;Kim, Sung Y.;Yoon, Mi Y.;Oh, Soo J.;Kim, Hye S.;Lee, Ja Y.;Kang, Sung A.;Lee, Kyung H.;Kim, Young C.
    • Toxicological Research
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    • v.16 no.4
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    • pp.293-301
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    • 2000
  • Toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance intragastrically at a dose of 0 mg/kg, 17 mg/kg, 52 mg/kg or 156 mg/kg for 91 consecutive days. No death or abnormal clinical sign was observed throughout the administration period. There was no difference in body weight gain, food intake or water consumption among different dose groups. Test sub-stance-related differences were not observed in urinalysis. In hematological results mean corpuscular hemoglobin (MCH) of low and high dose male group was increased. Prothrombin time of medium and high dose female group was decreased. A significant increase in serum total cholesterol was observed in both sexes of rats treated with a daily dose of 156 mg/kg, but all the other values obtained in serum chemistry appeared to be within normal ranges. A dose dependent increase in the relative liver and kidney weights was observed in both male and female rats. There were no gross pathological findings at terminal sacrifice. Microscopic histopathological examination did not show any lesion associated with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be greater than 17 mg/kg/day, but less than 52 mg/kg/day.

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Pharmacological and Toxicological review of Yukmijihwang-tang(Hwan) (육미지황탕(환)의 약리와 독성에 대한 문헌고찰)

  • Park, Yeong-Chul;Kim, Jong-Bong;Kook, Yoon-Boom;Lee, Sun-Dong
    • Herbal Formula Science
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    • v.20 no.1
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    • pp.13-24
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    • 2012
  • Objectives : Yukmijihwang-tang(Wan), a well-known formula for invigorating yin-particular kidney yin, was first recorded in "Xiao er Yao Zheng Zhi Jue", consisting of Radix Rehmanniae Preparata, Fructus Macrocarpii, Rhizoma Dioscoreae Oppositae, Poria, Rhizoma Alismatis and Cortex Moutan Radicis with dose proportion of 8:4:4:3:3:3. Although clinical trials have been lacking, various pharmacological actions for Yukmijihwang-tang has been identified newly using animal models. In addition, it was reported that Yukmijihwang-tang increases structural chromosome aberrations significantly in Chinese hamster lung cells. In this article, it is purposed that new studies for pharmacology and toxicology of Yukmijihwang-tang are reviewed. Insight into new studies of Yukmijihwang-tang at the cellular and animal levels will enhance our understanding of Yukmijihwang-tang against various diseases will provide new tools to diagnose and treat patients. Methods : Recent researches for Yukmijihwang-tang were reviewed and summarized in terms of pharmacological action and toxicity. All sources for review were based on recent studies loaded on data base of web sites such as Science Direct and National Center for Biotechnology Information. Results and Conclusions : Recently, reports showed that YMJ had antiaging effects, antioxidant and free radical scavenging activities, anti-renal hypertension and prevented tumors, and diabetes mellitus. However, there is little information on its safety except general toxicity, acute and sub-chronic oral toxicity, or genotoxicity. In addition, clinical trial for Yukmijihwang-tang was limited even though Yukmijihwang-tang has been used extensively in Korean traditional medicine. Thus, further studies are necessary to focus on safety evaluation and clinical trial for Yukmijihwang-tang.

The analysis of present condition and the method of medical treatment studies on Scolopendrid Herbal Acupuncture (오공약침(蜈蚣藥鍼)에 대한 연구현황분석(硏究現況分析)과 치료법(治療法)에 관한 연구(硏究))

  • Kim, Sung-Chul
    • Journal of Pharmacopuncture
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    • v.9 no.2
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    • pp.113-127
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    • 2006
  • Objectives : We review a result of studies until the present and suggest the method of medical treatment for the clinical treatment of Scolopendrid Herbalacupuncture. Methods : We analysis the paper of the bibliographic studies, the experiment studies and the clinical studies from 2001 developed Scolopendrid Herbalacupuncture and grope for the course of studies. Results : 1. Scolopendrid Herbalacupuncture is proved the clinical safety by the aninmal and human tests. 2. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition 3. Scolopendrid Herbalacupuncture has been a fine effect to the entrapment neuropathy and inflammatory. 4. Scolopendrid Herbalacupuncture was thought effective on a acute phase and to the excessive symptoms. The Sub-chronic toxicity experiment observing the response after hypodermic medication over 90 days, The Genetic-mutagenic toxity experiment and the clinical effect studies are necessary.

Therapeutic Effect of the GODEX on the Liver Chirrosis Induced by CCl4 and Ethanol in the Rat (사염화탄소와 에탄올에 의해 유발된 랫드의 간경변에서 GODEX (Hepadif-S capsule)의 치료 효과)

  • 신지순;정은용;이민호;강종구
    • Biomolecules & Therapeutics
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    • v.10 no.3
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    • pp.202-207
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    • 2002
  • The hepato-protective activity of the GODEX (Hepadif-s capsule) has been studied in the rats against $CCl_4$-ethanol induced liver toxicity. The rats were oral1y treated with $CCl_4$ (corn oil/ $CCl_4$ 1:1, 1 mg/kg). And one week passes, $CCl_4$(0.4 mg/kg) administered two times a week for 7 weeks. The drugs have been administered every two days for 4 weeks after $CCl_4$ injection. The experimental groups have consisted of the GODEX (250 mg/kg), Hepadif (200 mg/kg), DDB complex (DDB 50 mg/kg and garlic oil powder 50 mg/kg), DDB (50 mg/kg), and vehicle control respectively. There was a significant decrement on the serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in all treated groups. Specially, ALT level of GODEX and Hepadif only treated groups was decreased c1early. Also, serum albumin level was significantly enhanced in GODEX treated group compared with control and DDB treated groups. In histological results, hepatocellular vacuolar degeneration, lobular restructure and necrosis of bile duct were severely showed in control. But other treated groups showed centerilobular degeneration and mild hyper-plasia. Hepadif or DDB has a effects of the recovery on serum parameters and structure ill liver injury. When it was compared GODEX to Hepadif alone or DDB complex or DDB, it suggested to have the best activity of the liver recovery.

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.

Marine Ecotoxicological Evaluation on HNS Spill Accident : Nitric Acid Spill Case Study (HNS 유출사고가 해양생물에 미치는 생물독성 영향평가 : HNO3 유출사고 대상)

  • Kim, Tae-Won;Kim, Young Ryun;Jo, So Eun;Son, Min Ho;Lee, Moonjin;Oh, Sangwoo
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.21 no.6
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    • pp.655-661
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    • 2015
  • This study intends to evaluate the effect of nitric acid($HNO_3$) spill accidents on the marine ecosystem, while $HNO_3$ is known as one of the typical HNS. For this purpose, we performed (1) the growth inhibition test by using phytoplankton(Skeletonema costatum), (2) acute and chronic toxicity test by using invertebrate(Brachionus plicatilis and Monocorphium acherusicum), (3) fish(Cyprinodon variegatus) and (4) bacteria(Vibrio fischeri). In these tests, we observed the (1) pH changes induced by the nitric acid spill and (2) changes in nitrate($NO_3$) concentration disassociated from nitric acid after the accident, respectively. The toxicity test result on pH changes induced by $HNO_3$ shows that the no observed effect concentration(NOEC), lowest observed effect concentration(LOEC) and 50 % effect concentration($72h-EC_{50}$) values of M. acherusicum are pH 7 (0.3 mM), pH 5(1.1 mM) and pH 5.2(1.4 mM), respectively, indicating that M. acherusicum is the most sensitive species. The chronic toxicity test (population growth rate test) on $NO_3{^-}$ of B. plicatilis show that the NOEC, LOEC and $96h-EC_{50}$ are 5.9 mM, 11.8 mM and 32.6 mM, respectively, indicating that B. plicatilis is the most sensitive species. In conclusion, toxic effecst on the marine organism caused by the nitric acid spill accident is determined to be so slightly except for the most adjacent area of the ship in pH scale and such concentration of nitrate, to the extent of directly influencing the survival and reproduction of the marine organism, is determined practically not to be applicable in the typical accidents in the sea.

Lead Poisoning: Historical Aspects of a Paradigmatic "Occupational and Environmental Disease"

  • Riva, Michele Augusto;Lafranconi, Alessandra;D'orso, Marco Italo;Cesana, Giancarlo
    • Safety and Health at Work
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    • v.3 no.1
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    • pp.11-16
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    • 2012
  • Lead poisoning is one of the earliest identified and most known occupational disease. Its acute effects have been recognized from antiquity when this condition principally afflicted manual workers and slaves, actually scarcely considered by the medicine of that time. The Industrial Revolution caused an epidemic of metal intoxication, urging scientists and physician of that period to study and identify specific symptoms and organ alterations related to chronic lead poisoning. During the 20th century, the acknowledgment of occupational and environmental toxicity of lead fostered public awareness and legislation to protect health. More recently, the identification of sub-clinical effects have greatly modified the concept of lead poisoning and the approaches of medicine towards this condition. Nowadays, lead poisoning is rarely seen in developed countries, but it still represents a major environmental problem in certain areas. Consequently, it may appear as a paradigm of "occupational and environmental disease," and the history of this condition seems to parallel the historical development of modern "Occupational and Environmental Health" as a more complete medical discipline.

Evaluation of analgesic and antiinflammatory activity of Ophiorrhiza nicobarica, an ethnomedicine from Nicobar Islands, India

  • Chattopadhyay, Debprasad;Das, Sonali;Mandal, Asit Baran;Arunachalam, G;Bhattacharya, SK
    • Advances in Traditional Medicine
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    • v.7 no.4
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    • pp.395-408
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    • 2007
  • This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.