• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3973-3976
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• 2012

Background: The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. Materials and Methods: For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). Results: Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8.20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). Conclusions: Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

• 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.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.10
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• pp.1406-1413
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• 2016

This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

• Journal of Veterinary Clinics
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• v.38 no.1
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• pp.7-15
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• 2021

Kyungokgo-gamibang, Kyungokgo with Iksuyongjingo and Sparassis crispa, is a traditional Korean medicine used for restorative effects. This study aimed to evaluate the safety of Kyungokgo-gamibang in healthy beagle dogs. In the single-dose oral toxicity study, three beagle dogs were orally administered 2,000, 1,000, and 500 mg/kg of Kyungokgo-gamibang and were observed for 14 days. In the repeated-dose oral toxicity study, nine healthy dogs were orally administered 0.2g/kg of Kyungokgo-gamibang (n = 3, low-dose group), 1 g/kg of Kyungokgo-gamibang (n = 3, high-dose group), or normal saline (n = 3, control group) twice a day for 8 weeks. The hematological, serum biochemical, urine, protein, and lipid profiles were evaluated to investigate the adverse effects of the Kyungokgo-gamibang. During the study period, the dogs demonstrated no clinical signs and the hematological, serum biochemical, urine, protein, and lipid analyses revealed unremarkable findings. The study results suggest that Kyungokgo-gamibang can be safely administered to dogs without any adverse effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1324-1330
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• 2009

Lindera obtusiloba Blume (LO), which is widely distributed in Korea, Japan and China, has traditionally been used as a popular folk medicine for the treatment of fever, abdominal pain, bruise and extravation. The purpose of this study was to examine the toxicities of the single and 14-day repeated doses in Sprague-Dawley rats orally administrated with LO at doses of 0, 500, 1000, 2000 (14-day repeated toxicity test) and 5000 (single toxicity test) mg (dry weight)/kg of body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or organ weight among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally administered LO and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no evidences of histopathological alteration as well as abnormal gross finding mediated by single and 14 days treatments with LO. These results suggest that no observed adverse effect level (NOAEL) of the oral application of LO was considered to be more than 2000 mg/kg in rats under the conditions employed in this study.

• Korean Journal of Food Science and Technology
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• v.39 no.4
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• pp.470-475
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• 2007

Oplopanax elatus (O. elatus) is a tall deciduous shrub that has traditionally been used for σ eating a variety of ailments such as diabetes, coughling, rheumatism, gastro-intestinal disorders, and wounds. In order to examine the safety of the ethanol extracts of O. elatus, we performed a 14-day repeated-dose toxicity study with Sprague-Dawley rats. The rats were treated with daily doses of the D. elatus ethanol extracts by gavage at 0, 500, 1000, and 2000 mg/kg/day for 14 consecutive days. We recorded clinical signs of toxicity, body weight, hematology, organ weights, gross and histological changes in target organs, and clinical chemistry analysis data for all rats. There were no significant changes in body and organ weights during the experimental period. The hematological analysis and clinical blood chemistry data revealed no toxic effects from the O. elatus ethanol extracts. Pathologically, neither gross abnormalities nor histopathological changes were observed between the control and treated rats of both sexes. Collectively, these data suggest that the ethanol extracts of O. elatus have a high margin of safety.

• Toxicological Research
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• v.23 no.2
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• pp.151-158
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• 2007

tert-Butyl acetate is an organic solvent used for coatings, industrial cleaning, and surface treatment applications. This study investigated the potential adverse effects of tert-butyl acetate on pregnant dams and embryo-fetal development after maternal exposure on gestational days 6 through 19 in rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 500, 1,000, 1,500, and 2,000 mg/kg/day. All dams were subjected to a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 2,000 mg/kg, treatment-related clinical signs, including piloerection, abnormal gait, decreased locomotor activity, loss of fur, reddish tear, anorexia, nasal discharge, vocalization and coma, were observed in a dose-dependent manner. All dams died between the 2nd day and 5th day of treatment due to a severe systemic toxicity. At 1,500 mg/kg, minimal maternal toxicity including an increase in the incidence of decreased locomotor activity and loss of fur, and an increase in the weights of adrenal glands and liver was observed. On the contrary, no significant adverse effect on the embryo-fetal development was detected. There were no adverse effects on either pregnant dams or embryo-fetal development at <1,000 mg/kg. These results show that a 14-day repeated oral dose of tert-butyl acetate in rats caused a minimal maternal toxicity including increases in the incidence of clinical signs and the weights of adrenal glands and liver, but no embryotoxicity and teratogenicity at 1,500 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of tert-butyl acetate is estimated to be 1,000 mg/kg per day for dams and 1,500 mg/kg per day for embryo-fetal development.