• Title/Summary/Keyword: ACUTE TOXICITY

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Association Between Polymorphisms of Dihydrofolate Reductase and Gamma Glutamyl Hydrolase Genes and Toxicity of High Dose Methotrexate in Children with Acute Lymphoblastic Leukemia

  • Koomdee, Napatrupron;Hongeng, Suradej;Apibal, Suntaree;Pakakasama, Samart
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3461-3464
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    • 2012
  • Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

Acute Toxicity of Pentachlorophenol Sodium Salt, Potassium Dichromate, Sodium Azide to Neocaridina denticulata (Pentachlorophenol Sodium Salt, Potassium Dichromate, Sodium Azide에 대한 새뱅이(Neocaridina denticulata) 급성독성)

  • Lee, Jae-Woo;Moon, Ye-Ryeon;Yoon, Jun-Heon;Choi, Kyung-Hee;Han, Jin-Seok;Ryu, Ji-Sung
    • Environmental Analysis Health and Toxicology
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    • v.25 no.3
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    • pp.223-228
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    • 2010
  • Neocaridina denticulata is a small freshwater shrimp indigenous to Korea. As an indigenous species has long-adapted to particular water environments, the species can be a suitable indicator to assess environmental risks caused by hazard chemicals in the particular site. Thus Neocaridina denticulata, a small freshwater shrimp indigenous to Korea, is worth considering for a test species for such purpose. N. denticulata were exposed to pentachlorophenol sodium salt, sodium azide and potassium dichromate using automatic flow-through system for 96 hours. The 96 hr lethal concentrations ($LC_{50}$) of these chemicals were calculated as $0.53{\pm}0.09\;mg/L$, $2.40{\pm}0.61\;mg/L$ and $1.21{\pm}0.09\;mg/L$ respectively and showed relatively small deviation from repetitive test results. When compared with the toxicity values of other species for each chemical, N. denticulata had moderate or high sensitivity to the toxicity of these chemicals. It can be concluded that N. denticulata is a good test species to evaluate acute toxicity of various hazardous chemicals.

Acute/Subacute Toxicity of Nano Calcium (나노 칼슘의 급성/아급성 안전성 평가)

  • Jung, Eun Young;Suh, Hyung Joo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.1
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    • pp.29-34
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    • 2015
  • The objective of this study was to obtain data on the safety-in-use of nano calcium as a dietary supplement by assessing its acute and subacute oral toxicities in female and male Sprague-Dawley rats. A single oral dose of 5,000 mg/kg of nano calcium did not result in mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. For subacute toxicity study, nano calcium was administered orally at a dose of 1,000 mg/kg daily for 14 days. There were no significant differences in organ weights between control and treated groups of both sexes. Hematological analysis and blood chemistry revealed no toxic effects of nano calcium. Pathologically, neither gross abnormalities nor histopathological changes were observed. These results show that nano calcium possesses very low toxicity as indicated in a rat model.

Leaching and Acute Toxicity Test of Steel-making Slags for Media Contact Recycling (제강슬래그의 매체접촉형 재활용에 따른 중금속 용출특성 및 물벼룩 생태독성 평가)

  • Donghyun Kim;Bong Seok Cho;Won Sik Shin
    • Journal of Soil and Groundwater Environment
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    • v.29 no.1
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    • pp.72-83
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    • 2024
  • Most of the slags generated from steel-making industry in Korea are recycled into media-contact aggregates such as fill and cover materials. For their use as media-contact aggregates, the slags must meet not only the waste quality criteria, but also the Daphnia magna acute toxicity test criteria. In this study, Korean Leaching Test ES 06150.e (Korea), Japanese Leaching Test JIS K 0058-1(Japan), Detuch Leaching Test DIN 19529 (Germany), Toxicity Characteristic Leaching Procedure (USA) were conducted for batch leaching test of slags from 6 Korean steel-making companies. In addition, Korean Standard up-flow percolation test (ES 06151.1) mimicking field conditions was conducted to assess the impact of the slag leachate on the surrounding environment indirectly. Heavy metals such as Cr6+ and Zn2+ were detected from both extractant and leachate samples, but all of them did not exceed waste quality criteria of each country. However, Daphnia magna acute toxicity tests using the leachate samples from up-flow percolation test with slag alone and slag/natural soil conditions exceeded ecotoxicity standard (TU=2) due to their high pH (11.3-12.5). After neutralizing the pH of the slag leachate to 6.5~8.5, the Daphnia magna mortality and immobilization were reduced to satisfy ecotoxicity standard. As the reducing pH of slag leachate would be extremely difficult, appropriate recycling management considering the physicochemical characteristics of he slags should be stuided further.

Acute Subcutaneous Toxicity of DWP-311 in Rats (랫드에 대한 DWP-311의 급성피하독성시험)

  • Kwack, Seung-Jun;Kim, Hyung-Sik;Chun, Sun-Ah;Lim, So-Young;Park, Hyun-Sun;Han, Ha-Su;Hong, Chae-Young;Ahn, Mi-Young;Lee, Byung-Mu
    • Toxicological Research
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    • v.14 no.3
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    • pp.411-414
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    • 1998
  • The acute toxicity of DWP-311 was investigated in Sprague-Dawley rats. DWP-311 was subcutaneously administratered at dose levels of 595, 1,070, 1,930, 3,470, and 6,250mg/kg. In this study, we daily examined numbers of deaths, clinical signs, body weights, and pathological examinations for 7 days after administration of DWP-311. The results indicate that DWP-311 did not show any toxic effect in rats and the oral $LD_{50}$ value was over 6,250mg/kg in Sprague-Dawley rats.

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Studies on the Anti-inflammatory and Analgesic Activities of Ohjuksan (오적산(五積散)의 소염(消炎) 진통작용(鎭痛作用)에 관한 연구(硏究))

  • Moon, Young-Hee;Park, Young-Jun
    • Korean Journal of Pharmacognosy
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    • v.25 no.3
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    • pp.258-263
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    • 1994
  • Ohjuksan has been used for the treatment of cold and pantalgia in traditional medicine. The anti-inflammatory activity of the aqueous extract from Ohjuksan (OJSE) was investigated utilizing acetic acid-induced edema and adjuvant arthritis in rats. The effects of this agent on acute toxicity and acetic acid-induced writhing syndrome in mice were also examined. OJSE did not showed acute toxicity at 2400mg/kg (p.o.) and 1200mg/kg(i.p.) body weight. It was also showed to have significant analgesic action on the writhing syndrome in mice induced by 0.7% acetic acid at 300,600mg/kg body weight. It showed anti-inflammatory activity in 5% acetic acid-induced edema and adjuvant arthritis with oral administration in rats and exhibited significant preventive effect on edema at 300 and 600mg/kg(p<0.01). In the method of adjuvant arthritis, orally administered for 19 days, it inhibited the hind paw edema in rats with 300 and 600 mg/kg body weight from 5 th day to 19th day. These results suggest that OJSE had analgesic and anti-inflammatory action.

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Experimental Studies on the Safety of Whangryunhaedok-tang Extract Solution for Herbopuncture (중풍(뇌경색)환자의 한방치료(한약 및 약침요법)에 대한 객관적 지표 및 한방 신약개발에 관한 연구 - 황연해독탕(黃連解毒湯) 약침액(藥鍼液)의 성분분석(成分分析)과 급성독성(急性毒性)에 관한 실험적(實驗的) 연구(硏究) -)

  • Kim, Young-Suk;Kim, Chang-Hwan;Kim, Yong-Suk;Kim, Nam-Jae
    • The Journal of Korean Medicine
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    • v.20 no.2
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    • pp.54-62
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    • 1999
  • This experiment was carried out to study the safe utilization and standardization Whangryunhaedok-tang extract solution for herbopuncture on stroke patients. The test material was manufactured by water-alcohol method. The components of Whangryunhaedok-tang extract solution for herbopuncture were analyzed by HPLC. Mice were used for acute toxicity tests. The results were as follows. 1. In the berberine contents(%) of Whangryunhaedok-tang extract, berberine was 0.25%. 2. There were no abnormal findings in acute toxicity test treated with Whangryunhaedok-tang extract solution for herbopuncture and LD50 was not reached because no experimental animals were found dead throughout the study.

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Antimicrobial Activity and Acute Toxicity of Natural Rutin (천연 Rutin의 항균효과와 급성독성에 미치는 영향)

  • Rym, Kyo-Hwan;Eo, Seong-Kug;Kim, Young-So;Lee, Chong-Kil;Han, Seong-Sun
    • Korean Journal of Pharmacognosy
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    • v.27 no.4
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    • pp.309-315
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    • 1996
  • As part of our search for less toxic antimicrobial agents from natural resources, antimicrobial activity of rutin isolated from Sophora japonica was tested in vitro against four kinds of gram positive bacteria and four kinds of gram negative bacteria by serial broth dilution method. Among eight kinds of bacteria tested, the antimicrobial activity of rutin was the most potent against Mycobacterium smegmatis showing MIC of $375\;{\mu}g/ml$. The acute toxicity of rutin was examined in mice and rats. and $LD_{50}$ value administered intraperitoneally in mice was 650 mg/kg(Confidence limit: 894-1,473 mg/kg). There were no significant changes in serum biochemical values and histopathological changes as compared with those of control after intraperitoneal administration with rutin in rats.

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Acute Toxicity and Tissue Distribution of Cerium Oxide Nanoparticles by a Single Oral Administration in Rats

  • Park, Eun-Jung;Park, Young-Kwon;Park, Kwang-Sik
    • Toxicological Research
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    • v.25 no.2
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    • pp.79-84
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    • 2009
  • Cerium oxide nanoparticles (size: 30 nm) were prepared by the supercritical synthesis method, Acute oral toxicity and tissue distribution of the nanoparticles were evaluated by a single administration in rats. Oral administration of the nanoparticles to the rats did not lead to death when the animals were treated by a dose of 5 g/kg (high dose) as well as 100 mg/kg (low dose). Abnormal clinical signs, changes in serum biochemistry and hematology were not observed in high-dose treated group compared to the vehicle control group. Lesions in liver, lung and kidney were not observed in high-dose treated group by histopathological examination. Tissue distribution analysis in liver, kidney, spleen, lung, testis and brain was performed on day 1, day 7 and day 14 after treatment. The average values of the accumulated cerium oxide nanoparticles were elevated in all tissues but statistical significance was only shown in lung. Low levels of tissue distributions after a single oral administration seem to be the low bioavailability of the nanoparticles.

Acute Oral Toxicity of the Bark of Diospyros kaki in Mice (마우스에 대한 감나무 껍질의 급성경구독성시험)

  • Kim, Ju Hee;Park, Yun Jeong;Jo, Nam Sik;Kim, Dae Keun;Kim, Sang-Hyun;Shin, Tae-Yong
    • Korean Journal of Pharmacognosy
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    • v.45 no.2
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    • pp.181-185
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    • 2014
  • This study was carried out to investigate the acute toxicity of the bark of Diospyros kaki (Ebenaceae) in mice. The aqueous extract of the bark of Diospyros kaki (AEDK) was administered orally at a doses of 5 mg/kg, 50 mg/kg, 300 mg/kg and 2,000 mg/kg. In this study, number of deaths, clinical signs, body weights and pathological examinations were investigated after administration of AEDK. There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and AEDK treated groups in clinical signs, organ weights and gross pathological findings. AEDK did not show any toxic effect in mice.