• 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.

• 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.

• Journal of Pharmacopuncture
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• v.25 no.1
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• pp.46-51
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• 2022

Objectives: This study was performed to evaluate the skin irritation toxicity of processed sulfur. Methods: All experiments were conducted at Medvill (Korea), an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate skin irritation toxicity of processed sulfur, we divided the back of six rabbits into two control sites and two test sites. One of each of the two control and test sites was then designated abraded sites and intact sites. In test sites, 0.5 g of processed sulfur was applied to the back of the rabbit for 24 hours, and in control sites, 0.5 g of sterile distilled water was applied in the same way. We observed and evaluated mortality, weight, general symptoms, and skin irritation toxicity. This study was conducted with the approval of the Animal Ethics Committee (Approval number: IAC2020-1549). Results: In all experiments, no dead animals were observed. In all cases, skin coloration was observed at 24 hours after processed sulfur administration. This coloration lasted up to 48 hours and is believed to be the effect of the administration of test substances. Weight measurement indicated that weight was lost 72 hours after administration in three cases, but this is considered an accidental weight change. Normal weight gain was observed in the remaining subjects. In all animals, no skin irritation toxicity was observed, and the primary irritation index (P.I.I) was calculated as 0.0 according to Draize's evaluation method. Conclusion: The above findings suggest that it is relatively safe to apply a processed sulfur to the skin. Further research on this topic is needed to provide more specific evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1545-1549
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• 2014

Background: Published studies on clinical outcome of helical tomotherapy for lung cancer are limited. The purpose of this study was to evaluate clinical outcomes and treatment-related toxicity in inoperable non-small cell lung cancer (NSCLC) patients treated with helical tomotherapy in Korea. Materials and Methods: Twenty-seven patients with NSCLC were included in this retrospective study. Radiotherapy was performed using helical tomotherapy with a daily dose of 2.1-3 Gy delivered at 5 fractions per week resulting in a total dose of 62.5-69.3 Gy. We assessed radiation-related lung and esophageal toxicity, and analyzed overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and prognostic factors for overall survival. Results: The median follow-up period was 28.9 months (range, 10.1-69.4). The median overall survival time was 28.9 months, and 1-, 2-, and 3-year overall survival rates were 96.2%, 92.0%, and 60.0%. The median locoregional recurrence-free survival time was 24.3 months, and 1-, 2-, and 3-year locoregional recurrence-free survival rates were 85.2%, 64.5%, and 50.3%. The median distant metastasis-free survival time was 26.7 months, and 1-, 2-, and 3-year distant metastasis-free survival rates were 92.3%, 83.9%, and 65.3%, respectively. Gross tumor volume was the most significant prognostic factor for overall survival. No grade 4 or more toxicity was observed. Conclusions: Helical tomotherapy in patients with inoperable NSCLC resulted in high survival rates with an acceptable level of toxicity, suggesting it is an effective treatment option in patients with medically inoperable NSCLC.

• Journal of Pharmacopuncture
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• v.17 no.3
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• pp.7-15
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• 2014

Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W.) volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from $100-1000{\mu}g/mL$ of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and ${\alpha}$-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract's administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis. Conclusion: These results suggest that petroleum ether extract of W. volubilis has a non-toxic effect in Wistar female rats.

• Environmental Analysis Health and Toxicology
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• v.23 no.4
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• pp.267-276
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• 2008

Acute and chronic toxicities of sediment elutriate and surface water samples collected at Lake Shihwa were evaluated using standard toxicity testing organisms including Vibrio fischeri, Daphnia magna and Moina macrocopa. Acute exposure resulted in toxic effects in all surface water or sediment elutriate samples, except for those collected from the reed swamp and Okgu stream. The rainy season influenced the toxicity of the water samples, presumably either by dilution of point discharge or through introduction of non-point source contaminants through runoff. In the sediment, elutriate and surface water samples, copper was detected above potentially lethal concentration, which may in part explain the observed toxicity. Considering acute toxicities of the surface water streams that direct to the Lake Shihwa, efforts should be warranted to control and reduce discharge of point and non-point sources along Lake Shihwa.

• Toxicological Research
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• v.18 no.1
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• pp.1-11
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• 2002

3-Monochloro-1,2-propanediol(3-MCPD) is currently being a matter of concern because of its toxicity. 3-MCPD produced during the acid hydrolysis of soybean products has been reported to be mutagenic, neurotoxic, nephrotoxic and spermatotoxic. Howerer, the carcinogenicity of 3-MCPD is a controversial issue over the past several decades. 3-MCPD characteristically showed a variety of toxicities in reproductive system such as, decrease in sperm number and sperm motility, infertility, loss of sperm function, and weight decrease in ovary. Due to the toxicity of 3-MCPD, exposure to 3-MCPD has been proposed to be reduced to as low a level as technologically feasible. 3-MCPD can be detected in soy sauce or non-soy sauce products. The legal limit for 3-MCPD this year has been suggested to be 20 ppb（$\mu\textrm{g}$/kg）in the European Community. In Korea, the permissible level of 3-MCPD is expected to be 0.3 ppm. In this study, 3-MCPD was toxicologically evaluated in terms of risk assessment in humans.

• YAKHAK HOEJI
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• v.39 no.4
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• pp.450-460
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• 1995

The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.

• Journal of Food Hygiene and Safety
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• v.9 no.3
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• pp.111-116
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• 1994

The acute toxicity of orally administered Yan-Sheng health liquid (YSHL), water extracts from twelve Chinese drugs (Cervi Cornu, Lonicerae Flos, Foeniculi Fructus, Glycyrrhizae Radix, Liriopis Tuber, Raphani Semen, Bombyx, Ginseng Radix alba, Cinnamomi loureirii Cortex, Epimedii Herba, Zingiberis Rhizoma, Lycii Fructus) was evaluated in male and female Sprague-Dawley rats and ICR mice. Rats and mice aging 5 weeks were gavaged with 0, 2.0, 3.0, 4.4, 6.7, 10.0, 66.7, or 100.0 ml/kg of YSHL. No animal died by oral treatment and no toxic symptom was observed in the treated animals during 5 days. The body weight of the treated animals was not significantly different from the controls. The results of macroscopic examination on the organs of the treated animals revealed no abnormal findings. Therefore, it was concluded that YSHL was practically non-toxic when it was orally administered to rats and mice, and its LD50 was suspected to be greater than 100 ml/kg in rats and mice.

• Natural Product Sciences
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• v.17 no.4
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• pp.291-295
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• 2011

The present investigation evaluated the safety of the methanol extract from the fruit body of Phellinus pini Ames (PPA) by determining its potential toxicity after a subacute administration in rats. The extract was orally administered in doses of 1 g/kg, 2 g/kg, and 4 g/kg daily for 14 days to rats. Body weight, biochemical, and hematological parameters were determined at the end of 14 days of daily administration. The no-observed adverse effect levels (NOAEL) of the extract were 4 g/kg, when given by gavage routes. Daily oral administration of PPA extract for up to 14 days did not result in the death of significant changes in the body weight, hematological, and mainly biological parameters. In biological analysis, some significant changes occurred, including triglyceride and blood urea nitrogen (BUN), indicating that the PPA extract has liver and kidney-modulating activity. The PPA extract was found to be low or non-toxic in rats.