• Title/Summary/Keyword: relative toxicity

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Single and 28-day repeated dose toxicity studies of botulinum toxin type A in mice and rats (마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험)

  • Jeon, Tae-Won;Kim, Ji-Young;Hyun, Sun-Hee;Kim, Nam-Hee;Lee, Sang-Kyu;Kim, Chun-Hwa;Woo, Hee-Dong;Yang, Gi-Hyeok;Jung, Hyun-Ho;Jeong, Tae-Cheon
    • Korean Journal of Veterinary Research
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    • v.43 no.1
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    • pp.57-66
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    • 2003
  • Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

Cardiac Toxicity in Patients with Antidepressant Intoxication (항우울제 중독환자의 심장독성에 관한 연구)

  • Park, Jung-Taek;Choi, Se-Min;Oh, Young-Min;Oh, Joo-Suk;Kyoung, Yeon-Young;Cho, Hang-Joo;Choi, Kyoung-Ho
    • Journal of The Korean Society of Clinical Toxicology
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    • v.8 no.2
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    • pp.97-105
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    • 2010
  • Purpose: Although cardiac toxicity is a key parameter of significant toxicity, in antidepressant intoxication, there are few studies on the cardiac toxicity of serotonin reuptake inhibitor and the intoxication with the new generation of antidepressants. The aim of this study is to investigate the relative cardiac toxicity of serotonin reuptake inhibitor and intoxication with the new generation of antidepressants as compared with that of tricyclic antidepressant intoxication. Methods: We retrospectively reviewed the medical records of 109 antidepressant intoxicated patients who visited the Emergency Department from January, 2005 to December, 2009 to collect and analyze the demographic and clinical data. Sixteen patients were excluded. The enrolled seventy eight patients were classified into three groups: the tricyclic antidepressant group (TCA) (n=32), the selective serotonin reuptake inhibitor subgroup (SSRI) (n=28) and the new generation antidepressant subgroup (NGA) (n=18). Results: The demographic and clinical data of the SSRI and NGA groups were not significantly different from that of the TCA group. The QRS duration of the SSRI subgroup ($86.4{\pm}12.0$ msec) and the NGA subgroup ($91.8{\pm}11.9$ msec) was not significantly different from that of the TCA group ($90.0{\pm}13.5msec$) (p=0.598). The QTc interval of the SSRI group ($444.5{\pm}33.5msec$) and the NGA group ($434.9{\pm}35.9msec$) (p=0.260) were not significantly different from that of the TCA group ($431.2{\pm}44.1msec$) (p=0.287). Conclusion: Intoxication with SSRI and the new generation antidepressants seemed to show significant cardiac toxicity, like what is seen in tricyclic antidepressant intoxication. Clinicians must pay attention to SSRI and new generation antidepressant intoxication.

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Experimental Study on Brownian Coagulation in the Transition Regime (전이영역에서의 Brown 응집에 관한 실험적 연구)

  • Kim Dae-Seong;Lee Gyu-Won
    • Proceedings of the Korea Air Pollution Research Association Conference
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    • 2003.05b
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    • pp.355-356
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    • 2003
  • Coagulation is a process whereby particles collide with one another due to their relative motion, and adhere to form large particles. Coagulation caused by the random Brownian motion of particles is called Brownian coagulation. Many properties, such as light scattering, electrostatic charges, toxicity, as well as physical processes, including diffusion, condensation and thermophoresis depend strongly on their size distribution. Therefore, Brownian coagulation is substantially important in atmospheric science, combustion technology, inhalation toxicology and nuclear safety analysis. (omitted)

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Relative toxicites of aflatoxins for the risk assessment

  • Kim, Jae-Hyun;Kim, Tae-Myoung;Lee, Sook-Jin;Park, Cheol-Beom;Hong, Jin-Tae;Yoo, Hwan-Soo;Kang, Jong-Koo;Kim, Dae-Joong;Yun, Young-Won
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.58-58
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    • 2003
  • Aflatoxins are metabolites of fungi Aspergillus spp. that world-widely contaminate diverse foodstuffs including com and peanuts. It is well known that aflatoxins are highly mutagenic, carcinogenic and possibly teratogenic. Although aflatoxins have received the great attention among the various mycotoxins due to their potent hepatocarcinogenicity in certain species, it is extremely crucial to elucidate the relative toxicity and carcinogenicity of the types (B$_1$, B$_2$, G$_1$ and G$_2$) of aflatoxins for the risk assessment.(omitted)

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Feasibility Study of Docetaxel and Cyclophosphamide Six- Cycle Therapy as Adjuvant Chemotherapy for Japanese Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients

  • Abe, Hajime;Mori, Tsuyoshi;Kawai, Yuki;Tomida, Kaori;Kubota, Yoshihiro;Umeda, Tomoko;Tani, Tohru
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4835-4838
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    • 2013
  • Background: We compared treatment completion rates and safety of docetaxel and cyclophosphamide sixcycle therapy (TC6) with docetaxel followed by 5FU, epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Materials and Methods: We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer patients. The primary endpoint of this trial was toxicity. As second endpoints, the treatment completion rate and relative dose intensity were evaluated. Results: The TC6 and T-FEC group consisted of 22 and 21 patients, respectively. Concerning hematological toxicity, grade 3 or higher adverse reactions included neutropenia and febrile neutropenia. As non-hematological adverse events, exanthema and peripheral neuropathy were frequently reported in the TC6 group, whereas more patients of the T-FEC group reported nausea and vomiting. In TC6, the treatment completion rate was 86.4% and the relative dose intensity of docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively. Conclusions: These results suggest that TC6 is tolerable in Japanese, and that this regimen can also be performed in outpatient clinics. However, with the TC6 regimen, the compliance was slightly lower than with the T-FEC regimen, and supportive therapy needs to be managed appropriately.

An Adaptedness Assessment for Beach Nourishment Utilization of Dredged Materials in Hwasun-Port (화순항내 준설토사의 양빈재 유효활용을 위한 적합성 평가)

  • Choi, Jin-Hwan;Lee, Sang-Houck
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.4
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    • pp.2940-2944
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    • 2015
  • Dredged materials for effective use in Hwasun-port pollution analysis, Ni(nickel) in excess of the standard showed that the whole point. However, according to the revised standards effective utilization exceeds the reference value, even if no anthropogenic sources Pearl ratio less than 10% of the average weight of the ecotoxicological tests have passed, and if so it can be used to beach nourishment. Therefore, the average weight ratio of pearl and ecotoxicological tests were conducted by marine environment official test method. Mud to 5.37% of the average weight ratio lower than the reference value of 10% that was investigated. Ecotoxicity test using bioluminescent bacteria relative luminescence inhibition in the 0 to 9.13% with no toxicity was determined using benthic amphipods in the control and the test sample relative to the average survival rate is 0% with no toxicity was determined. Therefore, the revised effective use meets all the criteria that can be used to beach nourishment, so that the suitability was assessed.

Single and Four-Week Repeated Oral Toxicity Study of Antidiabetic Herb Extract Microcapsule in Sprague-Dawley Rats (항당뇨 한약추출고형물의 Sprague-Dawley 랫드를 이용한 단회 및 4주 반복투여 독성시험)

  • Kim, Young-Chul;Kim, Hye-Jeong;Kong, Min-Kyu;Lim, Ae-Kyoung;Kwon, Mi-Hwa;Kim, Kil-Soo;Lee, Gee-Dong
    • Toxicological Research
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    • v.23 no.1
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    • pp.87-96
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    • 2007
  • Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

4-week dose range finding toxicity test of Magnoliae Flos extract in Sprague-Dawley rats (Sprague-Dawley 랫드를 이용한 신이 추출물의 4주 반복 용량 결정 독성시험)

  • Park, Ju-Hyoung;Ahn, Eun-Kyung;Park, Kitae;Hwang, Min Hee;Cho, Young-Rak;Lee, Dong-Ryung;Choi, Bong-Keun;Oh, Joa Sub
    • Journal of Applied Biological Chemistry
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    • v.65 no.1
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    • pp.43-48
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    • 2022
  • Medicinal herb demonstrated in many pharmacological effects and recognized to be safe has been used for a long time. However, side effects including safety of medicinal herb have not been identified yet. The aim of the study was to estimate safety evaluation of Magnoliae Flos used for the treatment of pain, rhinitis, and pneumonia in Korea, China and Japan through four-week dose range finding toxicity test in male and female Sprague-Dawley rats. Magnoliae Flos was orally administered to male and female SD rats once a day for 28 days at 1,500 and 3,000 mg/kg. The safety evaluation was determined to examine clinical signs, mortality, body weight, food intake, hematology, serum biochemistry and relative organ weights and there were no significant changes related toxicity. Consequently, these findings indicates that Magnoliae Flos did not show any side effects including toxicity in dose range finding toxicity test and the no observed adverse effect level for Magnoliae Flos was estimated as more than 3,000 mg/kg.

Affirmative Effect of Hwaweo-jeon (Huayu-jian) in Osteoblast Cells and Tibia Fracture-induced Mice (화어전(化瘀煎)이 조골세포 및 경골골절 유발 생쥐의 골유합에 미치는 영향)

  • Lee, Soo-Hwan;Parichuk, Kira;Cha, Yun-yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.1
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    • pp.13-29
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    • 2020
  • Objectives This study was performed to decide the bone union effect of Hwaweo-jeon on tibia fractured mice. Methods In this study, laboratory experiments were implemented by the stage of in vitro and in vivo. In in vitro, MC3T3-E1 cells were treated with various concentration of Hwaweo-jeon extract (HWJ). To investigate effect of HWJ for osteoblast, relative mRNA expression of 5 substances (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], osteocalcin [OCN], osterix [OSX] and collagen type II alpha 1 chain [Col2a1]) was used as a marker of osteogenesis. In order to determine HWJ's effect for fracture healing, relative gene expression level of ALP, Runx2, OCN, OSX and Col2a1 were used to find out the influence to osteoblast. Furthermore, receptor activator of nuclear factor kappa-B ligand and osteoprotegerin relative mRNA expression were used to estimate the impact to osteoclast. Also, X-ray was used for the purpose of identifying bone union in tibia-fracture mouse model. Results In in vitro experiment, most part of relative mRNA expression were increased compared to control group. In in vivo and in vitro experiment, HWJ induced osteoblast activitation by verifying relative mRNA expression of 5 substances. And in vivo experiment, we can also identify that HWJ triggered osteoclast activation during early stage of tibia fracture. Furthermore, X-ray pictures show noticeable recovery of tibia fracture. Conclusions HWJ extract promotes bone union by facilitating the osteoblast. But, HWJ may occur liver & kidney toxicity over specific concentration. Therefore, when HWJ is applied to human body, doctors have to follow up the liver function test & renal function test of patient.

Chlorella vulgaris Has Preventive Effect on Cadmium Induced Liver Damage in Rats

  • Shim, Jae-Young;Om, Ae-Son
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.138-143
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    • 2008
  • We investigated if Chlorella vulgaris (CV) has protective effects on cadmium (Cd) induced liver damage in male Sprague-Dawley (SD) rats. Forty rats, aged 5 weeks old and weighed 90-110g, were divided into a control (with Cd free water), 50 ppm of $CdCl_2$ in drinking water treated groups (Chlorella 0% diet group (Cd/CV0%), Chlorella 5% diet group (Cd/CV5%) or Chlorella 10% diet group (Cd/CV10%). All the rats had freely access to water and diet for 8 weeks. The results show that body weight gain and relative liver weight had significantly lower in Cd/CV0%-treated group than in Cd/CV-treated groups. Hepatic Cd contents showed significantly less by feeding CV (P<0.05). Cd/CV0%-treated rats had significantly (P<0.05) higher hepatic T-MTs, and Cd-MTs concentrations, compared to Cd/CV5% or Cd/CV10% treated rats. The MT I/II mRNA was expressed in the liver of all experimental rats. Its expression was more increased in Cd/CV5%- or Cd/CV10%-treated rats, compared to control and Cd-treated rats. Thus, this study suggested that CV would have a protective effect on Cd-treated liver injury by the reduction of Cd concentrations and stimulation of Cd-MT binds in the liver. However, more studies are needed to identify the proper mechanism of CV and liver toxicity.