• Title/Summary/Keyword: Acute and repeated toxicity

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Inhalation Toxicity of 1-Bromoprpane (1-BP)

  • Kim, Hyeon-Yeong;Lee, Jun-Yeon;Lim, Cheol-Hong;Chung, Yong-Hyun;Han, Jung-Hee;Jeong, Jae-Hwang;Lee, Sung-Bae;Jhoon, Yoon-Sook;Lee, Yong-Muk
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.126-126
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    • 2001
  • The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ;(omitted)

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Toxicity Screening of Single Dose of Inorganic and Organic Arsenics on Hematological and Serum Biochemical Parameters in Male Cynomolgus Monkeys

  • Kim, Choong-Yong;Han, Kang-Hyun;Heo, Jeong-Doo;Han, Eui-Sik;Yum, Young-Na;Lee, Jin-Young;Park, Kyung-Su;Im, Ruth;Choi, Seong-Jin;Park, Jung-Duck
    • Toxicological Research
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    • v.24 no.3
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    • pp.219-225
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    • 2008
  • A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys(Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

The Evaluation of the Acute Toxicity and Safety of Verbenalin in ICR Mice

  • Hyejeong, Shin;Yigun, Lim;Jisu, Ha;Gabsik, Yang;Taehan, Yook
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.310-316
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    • 2022
  • Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study. Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted. Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group. Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

Alteration in Response to Chemicals Induced by Physical Exercise (육체운동에 의해 유발되는 화학물질에 대한 반응성의 변화)

  • 김영철
    • Toxicological Research
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    • v.18 no.3
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    • pp.215-226
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    • 2002
  • Acute or repeated physical exercise affects a large number of physiological parameters including hemodynamics, respiration, pH, temperature, gastrointestinal function and biotransformation, which determine the pharmacokinetics of drugs and chemicals. The rate and the amount of a chemical reaching the active site are altered by physical exercise, which results in significant changes in pharmacolosical/toxicological activity of the chemical. This aspect of physical exercise has vast implication in therapeutics and in safety evaluation, particularly for chemicals that have a low margin of safety. However there appears to be a wide inter- and intraindividual variation in the effects of physical exercise depend-ing on the duration, intensity and type of exercise, and also on the properties of each chemical. It is suggested that more studies need to be done to determine which factor(s) plays a major role in the disposition of chemicals in human/animals performing physical exercise. Certain chemicals induce severe toxicity due to metabolic conversion to reactive intermediate metabolites. it is suggested that repeated exercise may enhance the free radical scavenging system by increasing the activity of antioxidant enzymes. This area of research remain to be explored to elucidate the interaction of exercise and chemical on the antioxidant system.

Methylene Blue (메틸렌 블루)

  • You, Ji-Young
    • Journal of The Korean Society of Clinical Toxicology
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    • v.8 no.1
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    • pp.1-6
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    • 2010
  • Methylene blue is a very effective reducer of drug-induced methemoglobinemia. It has dose-dependent oxidation or reduction properties. In most cases, a dose of 1 to 2 mg/kg IV given over 5 minutes and immediately followed by a 15- to 30-mL fluid flush to minimize the local pain is both effective and relatively safe. The onset of action is quite rapid, and the effects are usually seen within 30 minutes. The dose may be repeated after 30 to 60 minutes and then every 2 to 4 hours as needed. The total dose should not exceed 7 mg/kg as a single dose or 15 mg/kg within 24 hours. Repeated treatment may be needed for treating compounds that have prolonged elimination or those compounds that undergo enterohepatic recirculation (e.g., dapsone). Methylene blue can cause dose-related toxicity. At high doses, methylene blue can also induce an acute hemolytic anemia and rebound methemoglobinemia. The reasons for treatment failure with methylene blue include ineffective GI decontamination, the existence of other forms of hemoglobin (e.g., sulfhemoglobin), a low or high dose of methylene blue and the toxicokinetics of some agents, such as aniline, benzocaine or dapsone.

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Successful Treatment of Infantile Fibrosarcoma Spinal Metastasis by Chemotherapy and Stereotactic Hypofractionated Radiotherapy

  • Lo, Cheng-Hsiang;Cheng, Shin-Nan;Lin, Kuen-Tze;Jen, Yee-Min
    • Journal of Korean Neurosurgical Society
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    • v.54 no.6
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    • pp.528-531
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    • 2013
  • We report a case of infantile fibrosarcoma in an 8-month-old boy manifested as a right-sided lower leg mass. Repeated local recurrence and distant metastasis were noted during the following three-year period. Whole body fluoro-deoxyglucose positron emission tomography scan revealed an asymptomatic metastasis involving the fourth lumbar vertebrae. The patient received chemotherapy (VAC regimen) with Cyberknife$^{(R)}$ stereotactic hypofractionated radiotherapy (26 Gy; 4 fractions). This treatment reduced tumor size by 23% without acute radiation toxicity even after 33 months. This case suggests that combining chemotherapy and this form of radiotherapy may be safe and effective against childhood spinal metastasis.

Study on the Toxicity of Jihwangbakhotang in Rats (지황백호탕(地黃白虎楊)의 독성효과(毒性效果)에 관(關)한 연구(硏究))

  • Na, Dal-Rye;Kim, Kyung-Yo;Lee, Jong-Duck
    • Journal of Sasang Constitutional Medicine
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    • v.9 no.2
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    • pp.203-225
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    • 1997
  • Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.

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Toxicity Assessment and Establishment Acceptable Daily Intake of Pyrimisulfan (피리미설판(Pyrimisulfan)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Park, Kyung-Hun;Park, Jae-Eup;Kwack, Seung-Jon;Kim, Young-Bum;Han, Bum-Seok;Son, Woo-Chen
    • The Korean Journal of Pesticide Science
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    • v.15 no.2
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    • pp.208-217
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    • 2011
  • Pyrimisulfan is a herbicide. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and also to determine its acceptable daily intake. Pyrimisulfan was excreted mostly by feces. It has low acute oral toxicity while it has no dermal, ocular irritation and skin sensitization (As the result of subchronic and chronic toxicity and carcinogenicity showed changes of hematology and liver.). Two-generation reproduction toxicity, genotoxicity, carcinogenicity and prenatal development toxicity were not proven. Therefore, the ADI for Pyrimisulfan is 0.1 mg/kg/ bw/day, based on the NOAEL of 10 mg/kg/ bw/day of 90-days repeated dose oral toxicity study in dogs while applying an uncertainty factor of 100.

Initial Risk Assessment of Disodium Disulphite in OECD High Production Volume Chemical Program

  • Sanghwan Song;Park, Yoonho;Park, Hye-Youn;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • v.18 no.1
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    • pp.23-29
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    • 2002
  • Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

Pharmacological Studies on Powdered Whole Part of Unossified Antler (분말녹용의 약물활성 연구(I))

  • Shin, Kuk-Hyun;Lee, Eun-Bang;Kim, Jea-Hyun;Chung, Myong-Sook;Cho, Sung-Ig
    • Korean Journal of Pharmacognosy
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    • v.20 no.3
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    • pp.180-187
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    • 1989
  • Systematic pharmacological studies on powdered whole part of unossified antler obtained from Cervus nippon Temminck var. mantchuricus have been carried out in mice and rats. Powdered antler, with a single oral administration, showed a very weak acute and subacute toxicity; its MLD being >5g/kg orally in mice. On daily oral treatments of the antler for 14 days, it did not cause any significant differences in body weight gain, various organ weights and serum transaminase activities compared to those of the control rats. Powdered antler, with a single oral administration, showed a remarkable analgesic activity as evaluated by writhing syndrome and tail-pressure test, a weak CNS depressant activity as well as a weak immunopotentiating action as evaluated by carbon clearance test in mice. Powdered antler, with repeated treatments, showed a moderate antifatigue effect against immobilized stress and showed significant increases in both adrenal weight and its ascorbic acid content in rats, suggesting that the mode of antifatigue effect of antler is related to adrenal and its components.

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