• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.222-227
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• 2002

Although there are a few reports concerning the side effects and toxicity of herbal medicines, there has not yet been any report concerning their causes, mechanisms or prevention. We investigated the internal reports concerning the side effects and toxicity of herbal medicines. In the findings, liver disorder (hepatic injury) was found in 7 cases, kidney disorders (nephropathy) were found in 12 cases, heart disorders were found in 4 cases and mineral-caused diseases were found in 2 cases. Besides, we found the major cause of the side effects and toxicity was drug abuse, such as over-dosage and long term medication. So, we hope this report brings more attention to the safety and toxicity of herbal medicines.

• Journal of Environmental Science International
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• v.20 no.7
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• pp.811-818
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• 2011

Daphnia Magna Stratus has been widely accepted as useful species for estimating the toxicity of chemicals to aquatic invertebrate and recommended as species for the testing chemicals from the international guideline as well as Korean guideline. The study was performed for the acute toxicity test by using water flea(D. Magna) for effluents from several wastewater treatment plants and drainage canals in GyeongBuk area. Five heavy metals, 1,4-Dioxane and Perchlorate were tested. Most Toxicity Units(TU) of Industrial wastewater effluents were less than 1 which means effluent was not toxic to D. Magna. However, effluents containing 1,4-Dioxane and Perchlorate were significantly toxic to D. Magna. Therefore, facilities should reduce the 1,4-dioxane since new regulations will force them after the year of 2011.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.199-208
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• 2000

Objectives : In order to investigate the toxicity of rats after oral administration of Eumcheonyijin-tang extract. Methods : The experimental animals were subdivided into control, short term administration group, and long term administration group. With changes of gross appearance, the histological changes of liver and kidney were observed. Blood chemical indexes used in this study were AST, ALT, total bilirubin, albumin, BUN and creatinine in serum. Results : In the long term administration group, histological changes were detected in the liver as centrolobular disposition of fatty tissue(adipose cell), and in serum test, AST, ALT increased at 21 days after administration group, serum total bilirubin were increased 21, 28 and 35 days after administration group. So it seems to induce toxicity. Kidneys of the long term administration group revealed histological changes : increasing of connective tissue and pyknosis of glomerulus cell were observed at 28 days after administration group, and in serum test, significant changes of albumin, BUN, and creatinine were admitted. So it seems to induce toxicity. Conclusions : In long term administration of Eumcheonyijin-tang toxicity was induced.

• Journal of Environmental Science International
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• v.11 no.9
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• pp.851-855
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• 2002

A comparison of Daphnia magna, Ceriodaphnia dubia and Simocephalus mixtus toxicity test was performed to study the relative sensitivities and discrimination abilities with both pore and elutriate water of Woopo wetland sediments. Sediment risk assessment has been done by standardized preparation method of pore and elutriate water described in the joint US EPA-US Army Crops of Engineers manual. Simocephalus mixtus which was obtained from Woopo wetlands in Korea was cultured and applied to sediment toxicity test. Water quality in Woopo wetland had great site and seasonal variations. S. mixtus was more sensitive than D. magna in heavy metal toxicity test. The toxicity results with S. mixtus reflected the water quality of elutriate and pore water. The results also suggested that S. mixtus could be used as a test organism in estimating potential risk of contaminated sediments.

• Toxicological Research
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• v.19 no.4
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• pp.259-266
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• 2003

Although 'Cinnamon' has been widely used for the food and biophamacy in the world, it's toxicity was not screened completely. Major component of 'cinnamon' is CB-OH and CB-PH. CB-PH has been reported to have antimutagenic effect. To investigate the toxicity of 2-o-Benzoylcinnama-Idehyde (CB-PH), repeated dose (4 weeks) oral toxicity test performed in SD rats. Results of repeated dose oral toxicity tests for 4 weeks (CB-PH; 500, 1000, 2000 mg/kg/day) suggested that the CB-PH treated group showed no significant toxicological findings with body weights, organ weights, hematological and histopathological findings. Therefore, these data indicated that the maximum tolerated dose of CB-PH was 2000 mg above/kg/day in the rats.

• Toxicological Research
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• v.34 no.1
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• Toxicological Research
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• v.28 no.1
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• pp.57-65
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• 2012

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

• Toxicological Research
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• v.23 no.4
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• pp.383-389
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• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3155-3160
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• 2016

Background: L-asparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/T-cell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations. Materials and Methods: In this retrospective, multi-center, observational study, Asian patients ${\geq}18$ years old who received ${\geq}1$ dose of the native E. coli ASNase from 2008 to 2013 were included. Patients were excluded if they did not receive ASNase. Endpoints of this study were development of specific toxicities, whether ASNase was discontinued or re-challenged, and developmentg of recurrent toxicity. All data analyses were performed using SPSS version 20.0. Results: A total of 56 patients were analyzed. Mean (${\pm}SD$) age was 36.2 (${\pm}15.2$) years old, with 62.5% being males, 55.4% with ALL and 28.6% with NK/T-cell lymphoma. Hypersensitivity (12.5%) was associated with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4 toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for non-CNS thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis. Hypersensitivity recurred in the 3 patients who were re-challenged with E. coli ASNase. Conclusions: ASNase is associated with a wide range of toxicities, with hypersensitivity being the most commonly observed among Asian adult patients.

• Toxicological Research
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• v.31 no.2
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• pp.181-189
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• 2015

In recent years, the use of both nano- and micro-sized lanthanum has been increasing in the production of optical glasses, batteries, alloys, etc. However, a hazard assessment has not been performed to determine the degree of toxicity of lanthanum. Therefore, the purpose of this study was to identify the toxicity of both nano- and micro-sized lanthanum oxide in cultured cells and rats. After identifying the size and the morphology of lanthanum oxides, the toxicity of two different sized lanthanum oxides was compared in cultured RAW264.7 cells and A549 cells. The toxicity of the lanthanum oxides was also analyzed using rats. The half maximal inhibitory concentrations of micro-$La_2O_3$ in the RAW264.7 cells, with and without sonication, were 17.3 and 12.7 times higher than those of nano-$La_2O_3$, respectively. Similar to the RAW264.7 cells, the toxicity of nano-$La_2O_3$ was stronger than that of micro-$La_2O_3$ in the A549 cells. We found that nano-$La_2O_3$ was absorbed in the lungs more and was eliminated more slowly than micro-$La_2O_3$. At a dosage that did not affect the body weight, numbers of leukocytes, and concentrations of lactate dehydrogenase and albumin in the bronchoalveolar lavage (BAL) fluids, the weight of the lungs increased. Inflammatory effects on BAL decreased over time, but lung weight increased and the proteinosis of the lung became severe over time. The effects of particle size on the toxicity of lanthanum oxides in rats were less than in the cultured cells. In conclusion, smaller lanthanum oxides were more toxic in the cultured cells, and sonication decreased their size and increased their toxicity. The smaller-sized lanthanum was absorbed more into the lungs and caused more toxicity in the lungs. The histopathological symptoms caused by lanthanum oxide in the lungs did not go away and continued to worsen until 13 weeks after the initial exposure.